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Review

Lipid-Based Nanovesicular Drug Delivery Systems

by
Tania Limongi
*,†,
Francesca Susa
†,
Monica Marini
,
Marco Allione
,
Bruno Torre
,
Roberto Pisano
and
Enzo di Fabrizio
Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy
*
Author to whom correspondence should be addressed.
†
Equal contribution.
Nanomaterials 2021, 11(12), 3391; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11123391
Submission received: 8 November 2021 / Revised: 7 December 2021 / Accepted: 13 December 2021 / Published: 14 December 2021
(This article belongs to the Special Issue Biobased Nanoscale Drug Delivery Systems)
Browse Figures
Versions Notes

Abstract

:
In designing a new drug, considering the preferred route of administration, various requirements must be fulfilled. Active molecules pharmacokinetics should be reliable with a valuable drug profile as well as well-tolerated. Over the past 20 years, nanotechnologies have provided alternative and complementary solutions to those of an exclusively pharmaceutical chemical nature since scientists and clinicians invested in the optimization of materials and methods capable of regulating effective drug delivery at the nanometer scale. Among the many drug delivery carriers, lipid nano vesicular ones successfully support clinical candidates approaching such problems as insolubility, biodegradation, and difficulty in overcoming the skin and biological barriers such as the blood–brain one. In this review, the authors discussed the structure, the biochemical composition, and the drug delivery applications of lipid nanovesicular carriers, namely, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, catanionic vesicles, and extracellular vesicles.

1. Introduction

Despite relevant technological improvements, developing an effective and safe drug can be a complex, low success rate, time-consuming, and costly practice. As reported on the official webpage of the US Food and Drug Administration (FDA), only a small number of treatment tools (active molecules, nanoparticles, and so on) proposed as skilled medical products, after early testing, result as eligible for further study. In 2020, the FDA’s Center for Drug Evaluation and Research (CDER) authorized 53 novel therapeutics, more than double what happened from 2006–2010. More in details considering the three major therapeutic areas, the new approved drugs are 18 (34%) cancer products, 8 (15%) Neurology products, and 6 (11%) infectious diseases treatments. The average projected peak sales of a just approved drug in 2020 was about USD 700 million, and this is below a long-term average of USD 1.3 billion and a median of USD 500 million [1].
The constant development of technologies and materials resulting from the collaboration between sectors such as bioengineering, physics, chemistry, materials science, pharmacology, and not least medicine, has allowed the advancement of increasingly efficient drug delivery tools. Researchers and clinicians from all over the world daily pursue the design and implementation of increasingly personalized, safe, and cheap care solutions as new pharmacologically active molecules and nanoparticles. Recently, the application of nanoparticles (NPs) has been established to develop drug delivery efficiency. Nanomaterials generally refer to a material characterized by having at least one dimension in the nanometer scale (1–100 nm) [2], include nano-drug delivery systems that thanks to their morphological, optical, mechanical, and electrical characteristics can improve drugs’ stability and solubility by extending their blood circulation time and enhancing their delivery efficiency.
Metallic, polymeric, organic, and inorganic nano scaled materials including dendrimers, nanotubes micelles, and quantum dots (QDs) have been recently assessed as drug delivery carriers (DDC) [3,4,5].
Among the already numerous nanoscale DDCs, nanovesicles represent highly-promising effective approaches to setting up therapies against cancer, inflammation infection, and degenerative disorders.
In this review, we described the most modern lipid-based nanovesicular systems, whether they are of biological or synthetic origin, used for the most distinct biomedical and clinical applications. We left liposomes, already the subject of numerous and recent scientific publications, out of the topics covered in this review, to make room for other lipidic nanovesicles, perhaps less known, but increasingly the target of studies for drug delivery applications such as niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, and catanionic vesicles. Last, but certainly not least, the type of Lipid NanoVesicles (LNV) discussed in this review are the extracellular vesicles (EVs) and their increasingly wide application as DDC of inorganic NPs, drugs, and nucleic acids. For each type of LNV category covered by the discussion, we provided an updated table listing in a very detailed way, the biochemical composition of each vesicle, its cargo, and the application for which it has been designed and studied referring to the in vitro and in vivo drug delivery applications of the last 10 years.

2. Proniosomes and Niosomes

Niosomes and proniosomes are LNV systems characterized by distinctive amphiphilic structures able to improve poorly soluble drugs bioavailability. Their uniqueness is in having a nonionic surfactant backbone while their multilamellar and unilamellar vesicles structures appear similar to that of liposomes [6] (Figure 1 and Figure 2).
It is assumed that lipophilic molecules are confined within the lipid bilayers while the hydrophilic ones are retained in the niosomes’ aqueous partitions. This efficient compartmentalization improves the stability of the enclosed drugs preventing their chemical and enzymatic degradation [7]. Proniosomes are nonionic dehydrated structured provesicles in the powdered form or in the gel states. Provesicles are water soluble dry free-flowing granular products that can be immediately rehydrated before use avoiding many issues related to aqueous vesicular dispersions. Proniosomes and niosomes can be produced by using cholesterol, non-ionic surfactants (Tween 20, 40, 80, Span 20, 40, 60, 80, 85), solvents as chloroform and methyl and ethyl alcohols and lecithin. Usually, surfactants utilized to produce niosomes and proniosomes are characterized by low aqueous solubility but Tween can be successfully used to produce micelles on hydration [8].
Niosomes are similar to liposomes, but they are cheaper, exhibit a higher stability, encapsulation efficiency, and permeability for small molecules, avoid the degradation of phospholipids by oxidation, and are easier to store and handle. Indeed, niosomes display some drawbacks, such as aggregation, fusion, and leakage of drugs, while proniosomes can overcome these issues contrasting leakage, aggregation, or hydrolysis of drugs while optimizing their storage and biodistribution, adding the possibility of sterilization, room temperature storage, and being rehydrated instantly to create niosomes [9].
Proniosomes have several pluses over niosomes, contrasting leakage, aggregation, or hydrolysis of drugs while optimizing their storage and biodistribution.
Although the first applications of non-ionic surfactant nanovesicles were cosmetic ones [10,11], in Table 1 and Table 2, we report the numerous and recent drug delivery applications for proniosomes and niosomes, respectively.
Thanks to their capability to store and deliver both hydrophilic and hydrophobic medications through topical, oral, transmucosal, pulmonary, ocular, and parenteral/intravenous administration, niosomes and proniosomes are increasingly used as vaccines and treatments for infection, inflammation, cancer, and many other acute or chronic diseases.

3. Ethosomes

Ethosomes were designed and developed in 2000 by Touitou et al. [108] as an advanced noninvasive passive lipid-based delivery system. As represented in Figure 3, these carriers are lipid bilayers composed of phospholipids, water, and high concentrations of ethanol which gives them remarkable transdermal permeability skills. Ethanol and lipid molecules act in the polar head group region increasing membrane fluidity and permeability. Ethosomes have significantly improved skin delivery, carrying the active compounds in the deeper layers of the skin in occlusive and non-occlusive conditions. In addition, they display high deformability, encapsulation efficiency, stability, biocompatibility, and a negative charge due to ethanol that leads to small vesicles size, enhancing the bioavailability of the compounds. Despite these advantages, there are some drawbacks caused by the volatile nature of ethanol, such as problems related to system instability, drug leakage, and skin irritation [109]. These vesicles are successfully used for topical administration of a considerable variety of drugs such as antifungals, antivirals, antibiotics, anti-inflammatories, and many others as detailed in Table 3.

4. Transfersomes

Many drug delivery systems have been designed over the past decades for transdermal administration, which offers many advantages over other routes thanks to its capability of escaping presystemic metabolism, tune drug release reducing variation in drug levels, enhancing pharmacological response. Compared to most other transdermal delivery methods including chemical permeation enhancers, sonophoresis, microneedles, lipid vesicles thanks to their distinctive composition can transport both hydrophilic and lipophilic drugs [140].
Among the LNV, transfersomes, first proposed in the early 1990s, are ultra-deformable elastic vesicles successfully employed as a non-occluded method able to permeate skin through the stratum corneum reaching the dermis and blood circulation [141]. As schematized in Figure 4, they are firstly characterized by an aqueous core enclosed by a lipid bilayer of amphipathic constituent as phosphatidylcholine, lecithin, or a mixture of lipids. In addition to a very low percentage of alcohol (3–10%), they are made with 10–25% of bilayer-softening complexes, surfactants, or edge activators as Tweens, Spans, sodium cholates, and deoxycholate. The appropriate phospholipids/surfactants ratio tunes transferosomes’ membrane elasticity reducing vesicles’ rupture chances through the skin [142,143]. By having edge activators in their structure, thanks to their remarkable elastic properties, transfersomes defeat many main liposomes’ weaknesses resulting in more apt to squeeze themselves through the skin barrier [144]. Despite these advantageous properties, transfersomes exhibit also some drawbacks, i.e., chemical instability due to the oxidative degradation and expensiveness in the precursors and manufacturing [143].
Thanks to their enhanced skin-penetration abilities, transfersomes are competent to set up skin drug storage area for continuous therapeutic molecules delivery releasing low, as well as high, molecular weight drugs as antioxidants, chemotherapy, anti-Inflammatory, and corticosteroids (Table 4).

5. Pharmacosomes

The name pharmacosomes refers to the amphiphilic, zwitterionic, stoichiometric complexes of polyphenolic compounds with phospholipids, as schematized in Figure 5. The success in the use of pharmacosomes is explained by the surface and bulk interactions of lipids with drugs since the latter possess an active hydrogen atom as –OH, -COOH, -NH2, which can be esterified to the lipid causing an amphiphilic compound [166,167].
The use of pharmacosomes in drug delivery has several advantages over that of other vesicles such as niosomes, transferosomes, and liposomes. More in detail, any active molecules in which a carboxyl group is present can be esterified without a spacer chain as opposed to those characterized by the presence of amino or hydroxyl groups which, in order to be esterified, require spacer groups. Pharmacosomes design is based on the phospholipids/water superficial and bulk interaction; the drug molecule and the connected lipid molecule, respectively, behave like the polar head group and the lipidic chain giving the molecule an amphipathic character. Thanks to their hydrophilic and lipophilic properties, these lipid LNV improve drugs’ dissolution in gastrointestinal fluid, increasing the bioavailability of low soluble treatments avoiding leak and rupture release [168,169]. Pharmacosomes’ in vivo pharmacokinetic performances are conditioned by vesicles’ dimension, by the drug molecule’s functional groups, by the lipids’ fatty acid chain length, and, last but not least, by the spacer groups’ availability. The high tunability of each of the components listed above makes these types of vesicles excellent candidates for the effective delivery of a wide range of active molecules including anti-cancer and anti-inflammatory remedies (Table 5) [170].
Among the few limitations relating to the use of pharmacoses, reference should be made to their susceptibility to hydrolyzation, fusion, or aggregation during storage or engineering processes [171,172].
Table
Table 5. Pharmacosomes’ drug delivery applications.
Table 5. Pharmacosomes’ drug delivery applications.
CompositionCargoApplicationReference
Doxifluridine and DOTAPmiR-122Treatment of hepatocellular carcinoma[173]
Etoricoxib and phosphatidylcholine Rheumatoid arthritis treatment[174]
Folic Acid-Modified 2-Deoxyglucose and amino ethanol Targeting anti-tumor therapy[175]
Ibuprofen and Phosphatidylcholine from soy Anti-inflammatory[176]
Levodopa, egg lecithin and chitosan Parkison’s treatment[177]
Naproxen and soy lecithin Rheumatoid arthritis treatment[178]
Rosuvastatin, soy lecithin and cholesterol Hyperlipidemia treatment[179]

6. Ufasomes

Unsaturated fatty acid vesicles preparation, more commonly known as ufasomes, was first reported in 1973 by Gebicki and Hicks [180]. In a controlled pH range, from 7 to 9, they are a closed lipid bilayered suspension, made from unsaturated fats and their ionized species. In detail, fatty acid molecules’ hydrocarbon tails are directed toward the deeper membrane layer while the carboxyl heads are in contact with water [181], as schematized in Figure 6. Oleic and linoleic acid (cis, is-9,12-octadecadienoic acid), the major ufasomes’ constituents, confer to these nanovesicles a more versatile nature than that of the other LNV, by ranking them between different nanosystems formed from double-chain amphiphiles and from single-chain surfactants micelles. Their biochemical composition makes them easily to assemble and real biocompatible [182,183]. By enhancing ufasomes stability with the identification of the appropriate fatty acid, pH range, and lipoxygenase amount, increasingly targeted and effective drug delivery solutions are being developed (Table 6).

7. Phytosomes

Although for a long time phyto-pharmaceuticals have a prominent position in the therapeutic scene, it should be emphasized how phyto-active constituents as phenolics, flavonoid, and terpenoids demonstrate considerable in-vitro bio-action but are still characterized by low in-vivo effectiveness due to their high molecular weight, low lipid solubility, and bioavailability [188]. Phytosomes nanovesicles originating by Phyto-Phospholipid Complex (PPC), have been developed as a capable strategy to improve natural drugs delivery and bioavailability. PPCs originate by the phospholipids’ polar head and active constituents’ interactions. The two long fatty acid chains do not take part in the formation of the complex, they can interchange encapsulating the polar region of complexes originating a lipophilic side when resuspended in water (Figure 7) [189].
Phytosomes have many structural and functional aspects in common with liposomes and tranferosomes such as the capability to improve the solubility of weakly soluble polyphenolic phytochemicals. Otherwise, phytosomes and transferosomes are more stable than liposomes in 4 °C and 25 °C aqueous media up to three months since liposomes should be freeze dried to preserve their stability. Phytosomes, as well as transferosomes, exhibit superior dermal penetration properties leading noticeable accumulation in the epidermis and dermis. Since the phytosomes configuration is grounded on the H-bond interaction between the phospholipid molecules’ polar moiety and the phytoconstituents, the laded compounds permanence is higher than in other lipid nanovesicles [190]. The numerous and very recent drug delivery applications collected in Table 7 show how phytosome nanotechnology will definitely get more efficient the ways of bioactive phytochemicals therapeutic and aesthetic delivery counteracting the bottlenecks of the low absorption and poor penetration rate across biological barriers improving herbal-originated compounds pharmacodynamic and pharmacokinetic and assets [190].

8. Catanionic Vesicles

An innovative class of biocompatible and biodegradable drugs lipidic nanovehicle is represented by the catanionic vesicles for their capability to improve the stability and cellular uptake of a wide range of active molecules [215]. These hybrid nanovesicles spontaneously form when unequal amounts of cationic and anionic single-tailed surfactants are dispersed in water [216] (Figure 8).
These nanovesicles are produced by using easily accessible cheap surfactants and, in comparison with phospholipid vesicles, are thermodynamically advantaged in terms of colloidal stability. Alkyl ammonium bromide and gemini surfactants such as bis-quaternary ammonium salts have been used for catanionic vesicles production; however, since they are cytotoxic and not biodegradable, the conjugation with safer molecules is being successfully considered [217]. Their low production costs, higher stability and drug loading capability, together with the fact that they suffer less from ruptures and pressure drops make them excellent drug delivery vehicles for vaccination and anti-microbial, cancer, and inflammatory applications (Table 8). Thus, although catanionic vesicles have a huge applicability in biomedicine, they can suffer safety problems due to their eventual low bio- and emocompatibility. Numerous ongoing researches point to the optimization of their morphology, hydrophobicity, and ionic charge by carefully choosing the proper surfactant and by tuning the anionic/cationic surfactant ratio eventually adding some suited additive [218].

9. Extracellular Vesicles

The most heterogeneous and versatile class of lipid vesicles is certainly that of extracellular vesicles (EVs) (Figure 9) including apoptotic bodies, microvesicles, and exosomes. These vesicles are ubiquitarian and can be isolated from cells culture media and from all the major biological fluid as urine, plasma, saliva, amniotic and cerebrospinal fluid, semen, among others [242,243,244,245]. Both apoptotic bodies and microvesicles, with dimensions ranging between 500 nm and 2 µm and from 50 nm to 1 µm, respectively, arise from plasma cell membrane outward blebbing and fragmentation. On the other side, exosomes, deriving from the endocytic pathway, have diameters between 30 to 120 nm [246]. Many authors reported about the EVs use in drug delivery since their surface is characterized by antigens, related to the parental cells, able to direct specific homing or targeting phenomena [247]. Although the EVS, as the main physio-pathological intracellular communication mediators, are already in origin able to transport miRNA, proteins, and other biological molecules, their morpho-functional and biochemical characteristics make them excellent candidates for post isolation nanotechnological modifications. In the last twenty years, numerous studies show the great potential of these vesicles in both the diagnostic and therapeutic fields [248]. Their high biocompatibility, low immunogenicity coupled with a superior loading capability make them proper tools for post isolation drug delivery load and engineering. In addition to a whole series of chemical or biological functionalization, many studies are referring to the possibility of loading them with cellular organelles such as mitochondria, NPs, drugs, and nuclei acids [249,250,251].
Although the intrinsic complexity related to the EVs’ size and natural (batch-to-batch) heterogeneity makes their drug delivery application much more complex than that with merely synthetic production systems, many exogenous EVs’ active molecules loading methods have been successfully proposed for the clinical EVs’ translation [252] (Table 9).
Many types of cell-derived exosomes, coming from both plant and human eukaryotic cells, have recently been used to successfully encapsulate inorganic NPs. The cargo can be either loaded by treating parental cells or by post EVs isolation engineering [299]. The potential benefits of a wide range of inorganic NPs-loaded EVs have been proven in various drug delivery applications as extensively listed in Table 10.
Since EVs are remarkably involved in genetic information transfer in normal and pathological states [325,326,327], it is not difficult to see their potential as engineered nucleic acids carriers for drug the treatment of ischemic stroke, myocardial infarction [328], traumatic brain injuries [329], and liver fibrosis [330].
The intrinsic properties of EVs such as low immunogenicity and safety make them a suitable candidate for gene cancer therapy with promising advantages with respect to the conventional chemotherapeutic treatments. EVs transfer their RNA or DNA cargo to the target cells with the aim to alter the tumoral genes information and act, e.g., as tumoral suppressors. In addition, the therapeutic properties of EVs-nucleic acids loaded can be further improved by tailoring their surface [331] in order to maximize specificity and successful delivery. In Massaro et al. [332] is reported a list of the ligands used for cancer therapy. Interestingly, attempts to conjugate RNAs to molecules such as cholesterol for EVs surface functionalization were reported [333,334], with the aim to improve loading control and delivery. Therapeutics effects of Plasmid DNA, mRNA, miRNA, and shRNA delivery EV-mediated were reported in Table 11 underlining how gene therapy combined with EVs delivery is a rapidly growing field for safe and effective precision medicine treatments.

10. Conclusions

It is well known that liposomes, assumed to be the oldest category of lipidic nanovesicles, have been broadly considered as the major candidates for biomedical and drug delivery applications. Despite their high biocompatibility and the ability to effectively carry both hydrophilic and/or hydrophobic active molecules to the target site, they still suffer some unresolved weaknesses such as brief shelf-life, low colloidal stability, and limited and expensive preparation methods [389]. The development of new drug delivery approaches has significantly boosted the design and the production of the just reviewed non-liposomal lipid nanovesicles. This new cohort of lipid vesicles can complement liposomes as alternative nanovesicular drug delivery systems and although recently implemented, they have all the chances to overspread as successful engineered nanomaterials.
Considering the existent non-liposomal LNV, those collected in this review, given their countless listed applications, have undoubtedly proved to be the most successful ones by reaching clinical use. Surely among the different types of LNV described in this review, those of cellular origin, the extracellular vesicles, are those that could also give future results closer to the needs of personalized medicine therapeutic plans. The possibility of isolating them from the same patient who is going to be treated reduces the likelihood of rejection phenomena both by increasing the compliance of the therapy and by reducing any adverse effects. Therefore, it would be foreseen that very soon, the LNV carrier’s production will scale-up from the lab scale to the industrial one issuing high-quality competitive outcomes.
In this regard, we would like to conclude with an update on the recent and promising use of lipid nanovesicles for the nucleic acids based-vaccine development. This application has been mainly oriented to the oncologic field, but recently, under the pressure of the latest terrible health emergency that has afflicted the entire globe, anti-viral applications have been reported. EV-based vaccines to deliver mRNA coding for specific molecules such as proteins or by the exposure of specific features on EVs surface have been designed. Since 2020, the SARS-CoV-2 pandemic has boosted additional efforts for the successful design of forceful vaccines [332,390]. Leading approved vaccines provide immunization by the viral Spike (S) protein, injected as purified proteins or codified by the administered mRNAs sequences and showing that “mRNA-based vaccines can fill the gap between emerging pandemic infectious disease and a bountiful supply of effective vaccines” [391]. The mRNA-based vaccine BNT162b2 was developed by Pfizer/BioNTech while the mRNA-1273 SARS-CoV-2 vaccine was developed by Moderna [392]. In Tsai et al. [364] was reported another approach for SARS-CoV-2 vaccines: exosomes are used to deliver mRNAs sequences with the aim to express not only the spike protein but also another artificial protein named “LSNME” and containing the viral spike, nucleocapsid, membrane, and envelope proteins. This approach has been tested on mice with promising results and, along with the many other applications reported in this review, confirmed the growing potential of lipid nanovesicles-mediated delivery as an effective tool for the translation of nanotechnology, bioengineering, and nanomaterials studies from research to clinic.

Author Contributions

Conceptualization, T.L. and F.S.; resources, T.L., F.S.; writing—original draft preparation, T.L. and F.S; writing—review and editing, M.M., B.T., M.A., R.P. and E.d.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data presented in this manuscript is available from corresponding author upon reseanable requests.

Conflicts of Interest

The authors declare no conflict of interest.

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Nanomaterials 11 03391 g001 550
Figure 1. Structure of proniosomes lipid vesicular systems.
Figure 1. Structure of proniosomes lipid vesicular systems.
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Figure 2. Structure of niosomes lipid vesicular systems.
Figure 2. Structure of niosomes lipid vesicular systems.
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Figure 3. Schematic structure of ethosome lipid vesicular system.
Figure 3. Schematic structure of ethosome lipid vesicular system.
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Figure 4. Schematic structure of transfersomes lipid vesicular system.
Figure 4. Schematic structure of transfersomes lipid vesicular system.
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Figure 5. Schematic structure of pharmacosomes lipid vesicular system.
Figure 5. Schematic structure of pharmacosomes lipid vesicular system.
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Figure 6. Schematic structure of ufasomes lipid vesicular system.
Figure 6. Schematic structure of ufasomes lipid vesicular system.
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Figure 7. Schematic structure of phytosomes lipid vesicular system.
Figure 7. Schematic structure of phytosomes lipid vesicular system.
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Figure 8. Schematic structure of catanionic vesicles.
Figure 8. Schematic structure of catanionic vesicles.
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Figure 9. Schematic structure of extracellular vesicles.
Figure 9. Schematic structure of extracellular vesicles.
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Table
Table 1. Proniosomes’ drug delivery applications.
Table 1. Proniosomes’ drug delivery applications.
CompositionCargoApplicationReference
Cholesterol, Span 60 and maltodextrinAceclofenacAnti-inflammatory in osteoarthritis[12]
Cholesterol, Span 60, maltodextrin and stearylamineAcemetacinAnti-inflammatory[13]
Cholesterol, lecithin, Span 60 and Span 40AtenololHypertension treatment[14]
Cholesterol, lecithin and Tween 80Atorvastatin calciumAnti- hyperlipidemic[15]
Cholesterol, lecithin and Span 40Boswellic acidAnti-inflammatory[16]
Cholesterol, lecithin and Span 60CaffeineMigraine treatment[17]
Cholesterol and Span 60CilostazoleAnti-platelet[18]
Cholesterol, lecithin and Span 60ClozapineTreatment of psychiatric disorders[19]
Cholesterol, lecithin and cremophor RHCurcuminAgainst ocular inflammation[20]
Cholesterol, Span 60 and Tween 80CiprofloxacinAnti-inflammatory[6]
Cholesterol, Span 40 TPGSDocetaxelAnticancer treatment[21]
Cholesterol and Span 60FamotidineH2 receptor antagonist[22]
Cholesterol, Sorbitol and Span 80FlurbiprofenAnti-inflammatory[23]
Cholesterol and Brij35D-limoneneCancer therapy[24]
Cholesterol, Span 60ItroconazoleAntimicotic against candida albicans[25]
Cholesterol, lecithin and cremophor RH 40LacidipineTreatment of hypertension and atherosclerosis[26]
Cholesterol, Tween 80, sorbitol and sucroseLetrozoleBreast cancer[27]
Cholesterol, Span 80 and lecithinLignocaine HydrochlorideDental anesthesia[28]
Cholesterol, Span 60 and Tween 60Lomefloxacin HClTreatment of bacterial conjunctivitis[29]
Cholesterol, lecithin and Lutrol F68LornoxicamAnti-inflammatory for rheumatoid arthritis, osteoarthritis and surgeries[30]
Cholesterol, lecithin and Span 60EmbelinAnalgesic and anti-inflammatory[31,32]
Span 40, Span 60, and Brij series 72FluconazoleManagement of dental pain[33]
Cholesterol, lecithin and Span 60NaproxenAnti-inflammatory[32]
Cholesterol, Span 60 and maltodextrinPentazocineManagement of cancer pain[34]
Cholesterol, Span 60, maltodextrin, pullulan and DPPHResveratrolControlling free radicals causing oxidative stress-induced cardiovascular diseases, atherosclerosis, cancer[35]
Cholesterol, Span 60, lecithin and stearylamineRisperidoneTreatment of schizophrenia and other psychiatric disorders[36]
Cholesterol, lecithin and Span 80TramadolAnti-inflammatory and antinociceptive[37]
Cholesterol, Span 60, lactose and mannitolVismodegibCarrier for the pulmonary route[38]
Table
Table 2. Niosomes’ drug delivery applications.
Table 2. Niosomes’ drug delivery applications.
CompositionCargoApplicationReference
Span 60, cholesterol and bile saltAcetazolamideDecrease ocular pressure in glaucoma patients[39]
Span 60, cholesterol, HMPC and carbopolAcetazolamide and carvedilolDecrease ocular pression in glaucoma patients[40]
Cholesterol, lecithin, Span 60 and Tween 60AcyclovirAntiviral[41]
Span60, Cholesterol and DCP or Span60, Cholesterol and TPGS[42]
Cholesterol and Span 40BetaxololGlaucoma treatment[43]
Ergosterol, Span 60 and Tween 60CarumAnticancer[44]
Cholesterol and Span/Tween 60CarvedilolCongestive heart failure, coronary artery disease, postmyocardial settings[45]
Bile salt-enriched vesicles, with 20% sodium cholate and 30% sodium taurocholateBeta receptor blocking activity to preclude angina and cardiac arrhythmias[46]
Cholesterol, Span 60 and Tween 60CephalexinAntibacterial[47]
Cholesterol, Span 40 and Tween 40CiprofloxacinAntibacterial[48]
Cholesterol, Span 60 and Tween 60[49]
Cholesterol, span and tween 20CurcuminAntinociceptive and anti-inflammatory[50]
Cholesterol, Span 80, PEGDaunorubicin and anti-CD123Treatment of acute myeloid leukemia[51]
Cholesterol, Span 40 and tween 40D-limoneneCancer therapy[52]
Pluronic L64, Tween 60, EMG 707 FerrofluidDoxorubicinTherapy against chronic myelogenous leukemia[53]
Pluronic L64, Cholesterol and transferrinCancer therapy[54]
Cholesterol, Span 40 and tween 40Doxorubicin and Hydrophobin-1Cancer therapy[55]
Cholesterol and Span 60Doxorubicin and N-lauryl glucosamineTargeted cancer therapy[56]
Cholesterol, Span 60 and Tween 60DoxycyclinTreatment of infection-associated prostate cancer[57]
Cholesterol and Span 60Doxycyclin hyclateManagement of ocular diseases[58]
Cholesterol, Span 60 and phospholipid 90GEmbelinDiabetes treatment[59]
Span 40, Span 60, and Brij series 72FluconazoleAntifungal treatments[60]
Cholesterol and Span 60FlurbiprofenAnti-inflammatory[61]
Cholesterol, Span 60 and Tween 65Gemcitabine and cisplatinLung cancer treatment[62]
Cholesterol, Span 40 and Tween 80LevofloxacinAntibacterial[63]
Cholesterol and Span 60LinezolidAntibacterial[64]
Cholesterol, Span 80 and Tween 80MethotrexateSolid tumor treatment[65]
Span 60, PVA and cremophor RH40[66]
Cholesterol and glucopyranoside[67]
Cholesterol and Span 40Metformin hydrochlorideAvoid Metformin-associated lactic acidosis in the treatment of diabetes mellitus[68]
Cholesterol and Span 60MinocyclinAntibacterial coating of dental implants[69]
Cholesterol and Tween 60MoxifloxacinAntimicrobial[70]
Cholesterol and tyloxapolNevirapineHIV treatment[71]
Cholesterol, Span 60 and SolulanC24N-palmitoylglucosamineBrain targeting of dynorphin-B[72]
Cholesterol, Span 60 and PEGSimvastatinAgainst myocardial ischemia/reperfusion injury[73]
Cholesterol, Span 20 and Span 60Pediatric transdermal dyslipidemia treatment[74]
Cholesterol and sorbitan monostearateTamoxifen citrateIncorporated in hydrogel as a pH-responsive drug delivery for breast cancer treatment[75]
Cholesterol and Span 20Tamoxifen citrate and doxorubicinBreast cancer treatment[76]
Cholesterol, Span60, PEG and TAT peptideTenofovirHIV treatment[77]
Cholesterol, Span 60 and Tween 40Timolol maleateGlaucoma treatment[78]
Cholesterol and Span 60[79]
Cholesterol and Span 40
Cholesterol and Span 60Timolol maleate and Brimonidine tartrateGlaucoma treatment[80]
Cholesterol, Span 60 and Tween 60TobramycinAntibacterial[81]
Cholesterol, Span 60 and Tween 40VancomycinAntibacterial[82]
Cholesterol and Span 60Antibacterial coating for bone plates[83]
Cholesterol and Tween 40ZolmitriptanMigraine treatment[84]
Cholesterol and Span 60Chlorotoxin and temozolomideTargeting and treatment of glyomas[85]
Cholesterol, Span 60 and PEGDoxorubicin, curcumin and tLyp-1 peptideGlioblastoma treatment[86]
PEG, Tween 80, OctadecylamineAkt 1 siRNA, Au NPs and ThymoquinoneTreatment of resistance in breast cancer[87]
Span 80 and PEGBBIQ [Toll-like receptor (TLR) 7 agonist] and D-1MT [Indoleamine2, 3-dioxygenase (IDO) inhibitor]Cancer vaccine[88]
Tween 80 and DTPA-ClBMP-7 plasmidBone regeneration[89,90]
Cholesterol and Span 60CD9 and CD63 tetraspaninsExosomes immunoassays[90]
Cholesterol, monopalmitin and Dicetyl phosphateInfluenza antigenVaccine and immune response[91]
Cholesterol, Span 80 and Tween 80NLS-Mu-Mu fusion proteinGene delivery[92]
Tween 60, DOTMA and lycopenepCMS-EGFP plasmidGene delivery to the brain[93]
Cholesterol, Span 20 and plier-like cationic lipid A (PCL-A)pDNA or siRNANucleic acid delivery[94]
DOTMA, Tween 20 and SqualenepEGFP, pGFP, MC-GFPTreatment of inherited retinal diseases[95]
Cholesterol and Span 20pH (Low) insertion peptide (pHLIP)Tumor targeting[96]
Cholesterol, Tween 20 and cationic lipid (N1,N1-dimyristeroyloxyethyl-spermine)plasmid DNA-encoding ovalbumin (pOVA)Skin vaccination[97]
2,3-di(tetradecyloxy)propan-1-amine cationic lipid, squalene and Tween 80Plasmid pCMS-EGFPDelivery of genetic materials to the retina[98]
Cholesterol and Span 60Protective antigen (PA) and PA domain 4 (D4) of Bacillus anthracisprophylaxis against anthrax[99]
Span 80, DOTAP, TPGS and indocyanine greensiGFP, anti-miR-138Promote osteogenesis in hMSCs, theranostic applications[100]
Cholesterol, Tween 85 and DDABsiRNAMelanoma treatment[101]
Cholesterol, Span 20 and plier-like cationic lipid B (PCL-B)siRNA against anti-apoptotic genes (Mcl-1, Bcl-2 and survivin) and doxorubicinBreast cancer therapy[102]
Cholesterol, Span 60 and PEGsiRNA/proteamine and iron superparamagnetic NPsBreast cancer therapy[103]
Cholesterol, DOTAP, PEG and Tween 60siRNA targeted the CDC20 mRNA, doxorubicin and quercetinCancer treatment[104]
Cholesterol and Tween 80Ciprofloxacin, rifabutin and lignin Ag NPsAntibacterial[105]
Cholesterol and Span 80Curcumin and Ag/Cu NPsAntibacterial[106]
Ergosterol, Span 60 and Tween 60Protamine-condensed DNA and Fe3O4 NPsMagnetic properties and cargo-targeted delivery[107]
Table
Table 3. Ethosomes’ drug delivery applications.
Table 3. Ethosomes’ drug delivery applications.
CompositionCargoApplicationReference
Soy lecithin5-Aminolevulinic acidTreatment of hypertrophic scars[110]
Soy phosphatidylcholine5-fluorouracilTreatment of skin cancers[111,112]
Soy lecithin and cholesterolApixabanAnticoagulant[113]
Soy phosphatidylcholineAzelaic acidTreatment of acne[114]
Soy phosphatidylcholine and cholesterolBoswellic acidAnti-inflammatory[115]
PhosphatidylcholineCaffeic acidAntioxidant[116]
Soy lecithinCurcumin and glycyrrhetinic acidPsoriasis treatment[117]
DSPE-PEG2000, hydrogenated soy phospholipids and cholesterolCurcumin, hyaluronic acid and CD44Psoriasis treatment[118]
Soy phosphatidylcholine, polyethylenimine and sodium cholateDoxorubicin and curcuminMelanoma treatment[119]
Lecithin and Tween 80FenretinideChemopreventive for breast cancer[120]
Soy phosphatidylcholine, cremophor-A25 and chitosanFerrous chlorophyllinPhotodynamic therapy for the treatment of squamous cell carcinoma[121]
Phospholipid 90GFisetinSkin cancers treatment[122]
Soy phosphatidylcholineFlurbiprofenAnti-inflammatory[123]
Soy phosphatidylcholineGriseofulvinAntifungal treatment[124]
Cholesterol and lecithinHyaluronic acidTransdermal delivery of drugs[125]
Soy phosphatidylcholine, cholesterolHRP IgGTransdermal delivery of vaccines[126]
Soy phosphatidylcholine, cholesterol and deoxycholic acidIndomethacinTreatment of pain and inflammation in rheumatoid arthritis[127]
Soy lecithin and cholesterolLuteolinAnti-tumor activity in hepatocellular carcinoma[128]
Soy lecithinMethotrexateTreatment of psoriasis[129]
Soy phosphatidylcholineMethoxsalenTreatment of vitiligo[130]
Soy phosphatidylcholine, cholesterol and mannitolPaenololAnti-inflammatory, antidiabetic and pain-relieving[131]
Soy phosphatidylcholinePaeoniflorinArthritis therapy[132]
Soy phosphatidylcholine and cholesterolPhenylethyl resorcinolSkin Lightening Applications[133]
Soy phosphatidylcholine, stearylamine and propylene glycolResveratrolAntioxidant[134]
PhosphatidylcholineRetinyl palmitateAcne treatment[135]
Soy phosphatidylcholineSulforaphaneTreatment of skin cancers[136]
Soy phosphatidylcholineTerbinafine hydrochlorideAntifungal treatment[137]
Phospholipid 90GThymoquinoneTreatment of acne[138]
Soy phosphatidylcholine and cholesterolThymosin β-4Wound repair[139]
Table
Table 4. Transfersomes’ drug delivery applications.
Table 4. Transfersomes’ drug delivery applications.
CompositionCargoApplicationReference
Soy lecithin and Span 80AceclofenacAnti-inflammatory in osteoarthritis[145]
Soy phosphatidylcholine and Tween 80BaicalinTreatment of skin wounds[146]
Soy phosphatidylcholine and Tween 80CarvedilolPrevent skin carcinogenesis[147]
Phospholipon® 90G and sodium cholateCilnidipineTreatment of hypertension[148]
Soy phosphatidylcholineDeferoxamineTreatment of pressure ulcers[149]
DPPC, cholesterol, TPGS and folateDocetaxelTreatment of glioblastoma multiforme[150]
Soy phosphatidylcholine and sodium cholateEpigallocatechin-3-gallate and hyaluronic acidAnti-aging and antioxidant[151]
Soy phosphatidylcholine and Tween 80Eprosartan mesylateTreatment of hypertension[152]
Soy phosphatidylcholine and Span 80Genistein (GEN-TF2)Therapeutic or preventive strategy against neurodegenerative diseases[153]
Soy lecithin and Sodium Lauryl SulphateIvabradine HClTreatment of stable angina pectoris[154]
Soy lecithin and Tween 80MangiferinTreatment of skin wounds[155]
Phospholipon (PL) 90H and Span 60NatamycinAntifungal[156]
Phospholipon 90 G® and sodium cholatePentoxifyllineTreatment of intermittent claudication and chronic occlusive arterial diseases[157]
Lecithin and Tween 20/80ResveratrolAntioxidant[158]
Soy phosphatidylcholine, Tween 80 and ceramide IIIRetinyl palmitateAntioxidant[159]
Soy phosphatidylcholine and emu oilTamoxifenTransdermal therapy for breast cancer[160]
Soy lecithin and Tween 80TaxifolinAntioxidant[161]
Soy phosphatidylcholine and Tween 80TocopherolAntioxidant[162]
Soya lecithin and Tween 80ZolmitriptanMigraine treatment[163]
Soy lecithin and sodium deoxycholateHuman growth hormoneTransdermal hormone delivery[164]
Egg phosphatidylcholine, stearylamine and Tween 20PnPP-19 peptideTreatment of erectile dysfunction[165]
Table
Table 6. Ufasomes’ drug delivery applications.
Table 6. Ufasomes’ drug delivery applications.
CompositionCargoApplicationReference
Cholesterol and oleic acidCinnarizineAntihistaminic activity[184]
Phosphatidylcholine from soy
and oleic acid		MinoxidilHypertension treatment[185]
Phosphatidylcholine from soy
oleic and linoleic acid		OleuropeinAntioxidant activity[183]
Oleic acid and tea tree oilOxiconazoleCandida albicans treatment[186]
Glyceryl oleateTerbinafine hydrochlorideCandida albicans treatment[187]
Table
Table 7. Phytosomes’ drug delivery applications.
Table 7. Phytosomes’ drug delivery applications.
CompositionCargoApplicationReference
PhosphatidylcholineAbutilon indicum and Piper longumHepatoprotective effect[191]
PhosphatidylcholineAnnona muricata L. aqueous extractTreatment of major depressive disorders[192]
Milk phospholipidsAscorbic acid and α-tocopherolAntioxidative[193]
PhosphatidylcholineBerberineDiabetes treatment[194]
PhosphatidylcholineChicoric acid and chlorogenic acid from the Echinacea plantAntioxidant activity[195]
Egg phospholipidChrysinDiabetes treatment[196,197]
LecithinDiosgeninLung cancer treatment[198]
PhosphatidylcholineDiosminVascular protection activity[199]
Phosphatidylcholine and piperineDomperidoneAnti-emetic effect[200]
LecithinEthanolic extract of leaves of Bombax ceibaHepatoprotective effect[201]
Lipoid® S45Flavonoids from Citrullus colocynthis, mormodica balsamina l. and mormodica dioica roxb.Diabetes treatment[202]
Lipoid® S100 and Phosal® 75 SAGenisteinHepatocellular carcinoma treatment[203]
Soy Hydrogenated PhosphatidylcholineIcariinTreatment of ovarian cancer[204]
PhosphatidylcholineMomordica charantia extractHypoglycemic effect[205]
DPPH and phosphatidylcholinePersimmon extractAntioxidative[206]
PhosphatidylcholinePropolisAntioxidant activity[207]
DPPCRutinAntioxidant for the prevention of liver inflammation[208]
LecithinSilymarinAntioxidant, hepatoprotective and anticancer activity[209]
LecithinTaxifolin rich fraction of Cedrus deodara bark extractBreast cancer treatment[210]
Soy Hydrogenated PhosphatidylcholineThymoquinoneLung cancer treatment[211]
PhosphatidylcholineTripterineCancer treatment[212]
Lipoid S100Tripterine and seleniumArthritis treatment[213]
PhosphatidylcholineUmbelliferonePhoto-protective and antioxidant activity[214]
Table
Table 8. Catanionic vesicles’ drug delivery applications. In the composition column, C is the cationic and A the anionic compound.
Table 8. Catanionic vesicles’ drug delivery applications. In the composition column, C is the cationic and A the anionic compound.
CompositionCargoApplicationReference
C: ester functionalized morpholinium and imidazolium-based surface active ionic liquids
A: sodium butyrate		CurcuminAntimicrobial activity[219]
C: CTAB
A: SDS		Lung cancer treatment[220]
C: CTAB
A: SDS		Diclofenac sodiumAnti-inflammatory[221]
Serine-based surfactants
C: 16Ser
A: 8-8Ser		DoxorubicinCancer treatment[222]
C: 4-cholesterocarbonyl-4′-(N,N,N-triethylamine butyloxyl bromide) azobenzene
A: SDS		Antioxidant activity[223]
C: CTAT
A: sodium dodecylbenzenesulfonate		Francisella tularensis lisateTularemia vaccine[224]
C: benzyldimethylhexadecyl
ammonium chloride
A: sodium 1,4-bis (2-ethylhexyl) sulfosuccinate		InsulinDiabetes treatment[225]
C: Azobenzene-based surfactant
A: sodium dodecylbenzenesulfonate		Paclitaxel and Bcl-2 siRNABreast cancer treatment[226]
C: hexadecyltrimethyl ammonium copper trichloride
A: SDS		Toluidine blue and Rose BengalAntimicrobial Photodynamic Therapy against Escherichia coli[227,228]
C: CTAC
A: SDS		Trans-resveratrolAntioxidant and radical scavenging activity[229]
C: arginine-based surfactants
A: sodium laurate, sodium myristate and 8-SH		 Antimicrobial and antibiofilm activity[218]
C: cetalkonium chloride
A: diclofenac sodium, flurbiprofen sodium or naproxen sodium		 Anti-inflammatory drug release from contact lenses[230]
C: chlorambucil prodrug
A: sodium bis (2-ethylhexyl) sulfosuccinate		 Cancer treatment[231]
C: Cytarabine hydrochloride
A: Sericin protein surfactant		 Cancer treatment[232]
C: CTAT
A: sodium dodecylbenzenesulfonate		 Extraction of cell surface components of Neisseria gonorrhoeae into the leaflet of the vesicles to create artificial pathogens for vaccines[233]
C: doxorubicin
A: gemini surfactant		 Cancer treatment[234]
C: DTAB
A: dioctyl sulfosuccinate sodium salt		 Drug delivery for cystic fibrosis[235]
C: hexamethylene-1,6-bis (dodecyldimethylammonium) dibromide
A: diclofenac sodium		 Antimicrobial activity[236]
C: methylimidazolium- or pyridinium-based surface active ionic liquids
A: sodium N-lauroyl sarcosinate		 Antimicrobial activity[237]
C: methylimidazolium- or pyridinium-based surface active ionic liquids
A: sodium bis(2-ethyl-1-hexyl) sulfosuccinate		 Antimicrobial activity[238]
C: NαNω-Bis(Nαcaproylarginine) α,ω-propyldiamide
A: Lichenysin		 Antimicrobial and antifungal activity[239]
C: N(π), N(τ)-bis(methyl)-L-Histidine tetradecyl amide
A: lysine-based surfactant Nα-lauroyl-Nεacetyl lysine or sodium myristate		 Antimicrobial activity[240]
C: N-dodecylamino-1-deoxylactitol
A: ketoprofen		 Anti-inflammatory activity[241]
Table
Table 9. Extracellular vesicles’ drug delivery applications.
Table 9. Extracellular vesicles’ drug delivery applications.
Parental cellCargoApplicationReference
EVs from HEK293T cellsAngiotensin converting enzyme II (ACE2)Protect from SARS-CoV-2 infection by competitively bound to virus against host cells[253]
Milk-derived exosomesAnthocyanidinsAnti-proliferative and anti-inflammatory in lung cancer[254]
Exosomes from breast and colorectal cancer cellsAspirinCancer therapy[255]
Exosomes from MIN-6 cellsBAY55-9837Increase insulin production for type 2 diabetes mellitus[256]
Exosomes from macrophagesBerberineSpinal cord injury treatment[257]
EVs from human umbilical cord mesenchymal stem cellsCannabidiolIncrease the therapeutic efficacy of doxorubicin in triple negative breast cancer[258]
Exosomes from umbilical cord-derived macrophagesCisplatinOvarian cancer cells treatment[259]
EVs from macrophagesCurcuminNeuroprotection and ischemia-reperfusion injury treatment[260]
Inhibit the phosphorylation of Tau protein[261]
Exosomes from mesenchymal stem cellsAttenuate the progression of osteoarthritis[262]
EVs from HEK293 cellsMyocardial infarction treatment[263]
Exosomes from bone marrow-derived mesenchymal stem cellsCerebral ischemia treatment[264]
Exosomes from HEK293 cellsCurcumin and RAGE-binding peptideAcute lung injury treatment[265]
EVs from smooth muscle cellsCystatin CProtection and healing of the nervous system in different neurotoxic conditions[266]
Exosomes from lung cancerDocetaxelNon-small cell lung cancer treatment[267]
Exosomes from cervical cancerCervical cancer treatment[268]
Exosomes from blood samplesDopamineParkinson’s disease treatment[269]
EVs from macrophagesDoxorubicinMetastatic ovarian cancer treatment[270]
Exosomes from mesenchymal stem cellsColorectal cancer treatment[271]
Exosomes from human gliomaGlioma treatment[272]
Milk-derived exosomesCancer treatment[273]
Exosomes from HEK293 cellsCancer treatment[274]
Exosomes from bone marrow-derived mesenchymal stem cellsOsteosarcoma treatment[275]
Exosomes from colon cancerColorectal cancer treatment[276]
Exosomes from human breast and ovarian cancerBreast and ovarian cancer treatment[277]
Exosomes from macrophagesEdaravonePermanent middle cerebral artery occlusion treatment[278]
Exosomes from human fetal lung fibroblastsErastinTriple-negative breast cancer therapy[279]
Exosomes from pancreatic cellsGemcitabinePancreatic cancer treatment[280]
EVs from human plasmaImperialineNon-small cell lung cancer treatment[281]
EVs from human umbilical vascular endothelial cellsMeta-tetra(hydroxyphenyl) chlorineCancer photodynamic therapy[282,283]
EVs from fibroblast cellsMethotrexateGlioblastoma treatment[284]
Exosomes from embryonic stem cellsPaclitaxelGlioblastoma treatment[285]
Exosomes from mesenchymal stem cellsCarcinoma treatment[286]
EVs from gingival mesenchymal stromal cellsCancer treatment[287,288]
Exosomes from macrophagesPulmonary metastases treatment[289]
Milk-derived exosomesLung cancer treatment[290]
EVs from bone marrow mesenchymal stromal cellsMalignant pleural mesothelioma treatment[291]
Exosomes from macrophagesMultiple drug-resistant cancer treatment[292]
EVs from lung cancer cellsPaclitaxel and oncolytic virusPrimary and metastatic cancer treatment[293]
EVs from neutrophil-like cellsPiceatannolAlleviated acute lung inflammation/injury and sepsis induced by lipopolysaccharide[294]
Exosomes from plasmaQuercetinRelieve symptoms of Alzheimer’s disease by inhibiting phosphorylation of Tau and reducing the formation of insoluble neurofibrillary tangles[295]
Exosomes from human ovarian cancerTriptolideOvarian cancer treatment[296]
Mannosylated exosomes from macrophagesVancomycin and lysostaphinEradication of intracellular quiescent MRSA[297]
Exosomes from fibroblastsWNT3ARepair of osteochondral defects[298]
Table
Table 10. Extracellular vesicles’ inorganic NPs delivery applications.
Table 10. Extracellular vesicles’ inorganic NPs delivery applications.
Parental CellCargoApplicationReference
Exosomes from human hepatocarcinomaDoxorubicin-loaded biomimetic porous silicon NPsCytotoxicity against bulk cancer cells and cancer stem cells[300]
Grapefruit EVsDoxorubicin-loaded heparin-based NPsGlioma treatment[301]
Exosomes from melanoma cellsGold NPsCancer treatment[302]
Exosomes from HEK293T cellsBlood-brain barrier penetration and brain disorders future treatments[303]
Exosomes from bone marrow mesenchymal stromal cellsNeuroimaging for various brain disorders[304]
Exosomes from mesenchymal stem cells[305]
Exosomes from breast cancer cellsGold iron oxide hybrid NPsMRI contrast agent and photodynamic therapy[306]
Exosomes from mesenchymal stem cellsIron oxide NPsMyocardial infarction treatment[307]
Wound repair[308]
Increase activation and migration ability of macrophage[309]
Tumor cell ablation via magnetically induced hyperthermia[310]
EVs from human umbilical vascular endothelial cellsPhotodynamic and hyperthermia therapy of prostate cancer[311]
Exosomes from macrophagesLaurate-functionalized Pt(IV) prodrug, human serum albumin, and lecithin NPsBreast cancer and metastatic breast cancer lung nodules treatment[312]
Exosomes from lung adenocarcinoma cellsMetal-organic frameworkDetection of the ATP level in living cancer cells, providing an efficient tool for the cell metabolism study[313]
Exosomes from triple negative breast cancer cellsDelivery of anticancer compounds[314]
Exosomes from HeLa cells[315]
Exosomes from lung cancer or gliomaPalladium nanosheetDeliver catalytic cargo directly to cancer cells[316]
Exosomes from triple negative breast cancer cellsPLGA NPsCancer therapy[317]
Exosomes from lung carcinoma cells [318]
EVs from Staphylococcus aureusIntracellular delivery of antibiotics for intracellular pathogen-associated complications treatment[319]
Exosomes from breast cancerQuantum dots of vanadium carbideCancer photothermal therapy[320]
Exosomes from hepatocellular carcinomaSilver and iron NCsCancer bioimaging[321]
Exosomes from macrophagesSPIONs and curcuminSynergistic antitumor therapy in gliomas[322]
Exosomes from plasmaSuperparamagnetic magnetite colloidal nanocrystal clustersCancer treatment[323]
EVs from KB cellsZinc oxide NCsCancer treatment[324]
Table
Table 11. Extracellular vesicles’ nucleic acids delivery applications.
Table 11. Extracellular vesicles’ nucleic acids delivery applications.
Parental CellCargoApplicationReference
Microvesicles from breast cancer cellsMinicircle DNA encoding a thymidine kinase /nitroreductase fusion proteinBreast cancer therapy[335]
EVs from mice melanoma cellsPlasmid DNA coding for ESAT-6Promote antitumor activity of dendritic cells[336]
EVs from human brain endothelial cells and macrophagesPlasmid DNA encoding for brain-derived neurotrophic factorProtection of the brain endothelium increasing endothelial ATP levels[337]
EVs from macrophage cellsTripeptidyl peptidase-1-encoding plasmid DNALysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease treatment[338]
EVs from red blood cellsAnti-miR-125b ASOs and Cas9 mRNACancer treatment[339]
Exosomes from mouse neuronal cellsmiR-21-5pSuppression of autophagy after a traumatic brain injury[340]
EVs from frozen human plasmamiR-31 and miR-451aPromoted apoptosis of hepatocellular carcinoma[341]
Exosomes from human bone marrow mesenchymal stem cellsmiR-101-3pOral cancer treatment[342]
Exosomes from bone marrow mesenchymal stem cellsmiR-124Promote neurogenesis after ischemia[343]
EVs from human adipose tissue-derived mesenchymal stromal/ medicinal signaling cellsmiR-125bInhibits hepatocellular carcinoma proliferation[344]
Exosomes from normal intestinal epithelial FHC cellsmiR-128-3pIncrease chemosensitivity of oxaliplatin-resistant colorectal cancer[345]
Exosomes from HKT293T cellsCurcumin, saponin, MiR-143Engineered exosomes for anti-HIV agents delivery to solid tissues[346]
Exosomes from human umbilical cord mesenchymal stem cellsmiR-145-5pInhibit adenocarcinoma progression[347]
EVs from bone-marrow mesenchymal stem cellsmiR-146aUlcerative colitis treatment[348]
EVs from human mesenchymal stromal cellsmiR-146a-5pPrevent group 2 innate lymphoid cells -dominant allergic airway inflammation[349]
Exosomes from human umbilical cord mesenchymal stem cellsmiR-148b-3pSuppress breast cancer progression[350]
Exosomes from mesenchymal stem cellsmiR-199aInhibit the growth of glioma by down-regulating AGAP2[351]
Exosomes from endothelial progenitor cellsmiR-210Protect endothelial cells against hypoxia/ reoxygenation injury improving mitochondrial function[352]
EVs from mesenchymal stem cellsmiR-210
Promote angiogenesis in myocardial infarction[353]
EVs from bone mesenchymal stem cellsmiR-216a-5pPromote the proliferation of chondrocytes in osteoarthritis[354]
EVs from human umbilical cord mesenchymal stem cellsmiR-302aTherapy of endometrial cancer[355]
EVs from mesenchymal stem cellsmiR-379Therapy for metastatic breast cancer[245]
EVs from adipose tissue-mesenchymal stromal cellsmiR-424-5pTherapy for triple negative breast cancer[356]
Exosomes from HEK-293T cellsmiR-497Inhibit lung cancer growth and angiogenesis[357]
Exosomes from CRC cellsmiR-567Reverse chemoresistance to Trastuzumab in breast cancer[358]
EVs from HEK-293T cellsmiR-1252-5pDownregulation of heparanase to enhance the chemosensitivity to Bortezomib in multiple myeloma[359]
EVs from HEK-293T cellsmiRNA-21Myocardial infarction treatment[360]
Exosomes from breast cancermiRNA-126Inhibit the formation of lung cancer metastasis[361]
EVs from glioblastoma stem-like cellsmiRNA-139Downregulation of glioblastoma[362]
Exosomes from mesenchymal stem cellsmiRNA-584-5pGliomas treatment[363]
Exosomes 293F cellsmRNASARS-CoV-2 vaccine[364]
Exosomes from HEK-293T cellsCatalase mRNAAttenuated neurotoxicity and neuroinflammation in Parkinson’s disease[365]
EVs from HEK-293T cellsCytosine deaminase fused to uracil phosphoribosyltransferase mRNAGlioblastoma treatment[366]
EVs from HEK-293T cellsHChrR6 mRNAConvert CNOB into MCHB for the treatment of cancers[367]
Exosomes from mesenchymal stem cells, dendritic cells or HEK-293T cellsPTEN mRNARestore tumor-suppressor function in PTEN deficient gliomas[368]
EVs from non-pigmented ciliary epithelium cellsanti-fibrotic (SMAD7) siRNALower intraocular pressure in primary open-angle glaucoma[369]
Exosomes from autologous breast cancer cellsCationic bovine serum albumin conjugated siS100A4Suppress postoperative breast cancer metastasis[370]
EVs from murine neuroblastoma cell line and dendritic cellsCholesterol-conjugated siRNAsHuman antigen R silencing for cancer treatment[334]
Exosomes from HEK-293T cellsc-Met siRNAReverse chemoresistance to cisplatin in gastric cancer[371]
Exosomes from HEK-293T cellsHepatocyte growth factor (HGF) siRNAInhibitory effect on tumor growth and angiogenesis in gastric cancer[372]
EVs from mesenchymal stem cells derived from umbilical cord Wharton’s jellyHydrophobically modified asymmetric siRNAs conjugated with cholesterolHuntingtin silencing in neurons[333]
Exosomes from glioblastoma cells[373]
Exosomes from human neuroblastoma cellsHeat shock protein-27 (HSP27) siRNADecrease of cell differentiation toward mature neuron in neuroblastoma[374]
Exosomes from urine-derived induced pluripotent stem cellsICAM-1 siRNAAlleviating inflammation of pulmonary microvascular endothelial cells[375]
Exosomes from HEK-293T cellsKRAS siRNAInhibition of tumor growth[376]
EVs from astrocytesLincRNA-Cox2 siRNALipopolysaccharideinduced microglial proliferation for treatment of CNS disorders[377]
Exosomes from mesenchymal stem cellsPTEN siRNAPromote recovery for spinal cord injury individuals[378]
EVs from red blood cellsP65 and Snai1 siRNAInhibit renal inflammation and fibrosis for acute kidney injury treatment[379]
EVs from HEK-293T cellsRAGE siRNAAttenuated inflammation in myocarditis[380]
Exosomes from bone-marrow-derived mesenchymal stem cellssiGRP78Suppress Sorafenib resistance in hepatocellular carcinoma[381]
Exosomes from bovine milksiKRASLung tumor treatment[382]
EVs from different cell linessiRNAReducing the therapeutic dose of siRNA for different pathologies[383]
EVs from human umbilical cord mesenchymal stem cellssiRNA-ELFN1-AS1Inhibit colon adenocarcinoma cells proliferation[384]
Exosomes from normal human foreskin fibroblastsiRNA or short hairpin RNA specific to oncogenic KrasG12DPancreatic ductal adenocarcinoma treatment[385]
Exosomes from HEK-293T cellsTransient receptor potential polycystic 2 (TRPP2) siRNAReduce the epithelial-mesenchymal transition in pharyngeal squamous carcinoma[386]
Exosomes from brain endothelial bEND.3 cellsVascular endothelial growth factor (VEGF) siRNAKnockdown of VEGF in brain cancer cells[387]
Exosomes from HEK-293T cellsDifferent viral products including Ebola Virus VP24, VP40 and NP, Influenza Virus NP, Crimean–Congo Hemorrhagic Fever NP, West Nile Virus NS3, and Hepatitis C Virus NS3Exosomes-based vaccines[388]
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Limongi, T.; Susa, F.; Marini, M.; Allione, M.; Torre, B.; Pisano, R.; di Fabrizio, E. Lipid-Based Nanovesicular Drug Delivery Systems. Nanomaterials 2021, 11, 3391. https://0-doi-org.brum.beds.ac.uk/10.3390/nano11123391

AMA Style

Limongi T, Susa F, Marini M, Allione M, Torre B, Pisano R, di Fabrizio E. Lipid-Based Nanovesicular Drug Delivery Systems. Nanomaterials. 2021; 11(12):3391. https://0-doi-org.brum.beds.ac.uk/10.3390/nano11123391

Chicago/Turabian Style

Limongi, Tania, Francesca Susa, Monica Marini, Marco Allione, Bruno Torre, Roberto Pisano, and Enzo di Fabrizio. 2021. "Lipid-Based Nanovesicular Drug Delivery Systems" Nanomaterials 11, no. 12: 3391. https://0-doi-org.brum.beds.ac.uk/10.3390/nano11123391

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