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Pharmaceutics
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Micro and Nano Encapsulation Techniques
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Micro and Nano Encapsulation Techniques

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 September 2018) | Viewed by 112421

Special Issue Editors

Prof. Dr. Bice Conti

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Guest Editor
Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Interests: tissue engineering; nanomedicine; drug delivery; nanocarriers; electrospinning
Special Issues, Collections and Topics in MDPI journals
Dr. Ida Genta

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Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: drug delivery; polymer nanoparticles; microspheres; biodegradable polymers; thermosensitive hydrogel; 3D bioprinting; tissue regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, micro- and nanoparticles have generated a great deal of interest in the pharmaceutical area. They demonstrate several advantages, such as the ability to encapsulate a wide variety of therapeutic agents, including peptides, proteins, genes, and to control, tune and target drug release. While the first generation of products have been successfully commercialized, recent advances in material design and knowledge of disease biological basis are contributing to the development of more sophisticated systems, such as theranostic tools or active targeted nanocarriers mostly focused on treating severe and harming pathologies such as cancer and immunological diseases.

This Special Issue’s goal is to capture the current state-of-the-art and contemporary progress in this field. Suggested topics are: Manufacturing processes including challenges and industrial scale-up; regulatory approaches to micro and nanoparticulate drug delivery systems including generic medicinal products; new approaches in targeted drug delivery; and new micro and nanoparticulate systems characterization techniques including imaging.

Prof. Bice Conti
Prof. Ida Genta
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanoparticles
  • Microparticles
  • Liposomes
  • Dendrimers
  • Polymer conjugated
  • Polyplexes
  • Drug delivery systems
  • Manufacturing techniques
  • Polymers
  • Biomaterials

Published Papers (16 papers)

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Research

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13 pages, 2888 KiB  
Article
Xylan-Based Hydrogels as a Potential Carrier for Drug Delivery: Effect of Pore-Forming Agents
by Minmin Chang, Xinxin Liu, Ling Meng, Xiaohui Wang and Junli Ren
Pharmaceutics 2018, 10(4), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040261 - 05 Dec 2018
Cited by 15 | Viewed by 3732
Abstract
Pore-forming agents have a significant influence on the pore structure of hydrogels. In this study, a porogenic technique was employed to investigate the preparation of macroporous hydrogels which were synthesized by radical copolymerization of carboxymethyl xylan with acrylamide and N-isopropylacrylamide under the [...] Read more.
Pore-forming agents have a significant influence on the pore structure of hydrogels. In this study, a porogenic technique was employed to investigate the preparation of macroporous hydrogels which were synthesized by radical copolymerization of carboxymethyl xylan with acrylamide and N-isopropylacrylamide under the function of a cross-linking agent. Six kinds of pore-forming agents were used: polyvinylpyrrolidone K30, polyethylene glycol 2000, carbamide, NaCl, CaCO3, and NaHCO3. The application of these hydrogels is also discussed. The results show that pore-forming agents had an important impact on the pore structure of the hydrogels and consequently affected properties of the hydrogels such as swelling ratio and mechanical strength, while little effect was noted on the thermal property of the hydrogels. 5-Fluorouracil was used as a model drug to study the drug release of the as-prepared hydrogels, and it was found that the drug release was substantially improved after using the NaHCO3 pore-forming agent: a cumulative release rate of up to 71.05% was achieved. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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18 pages, 2132 KiB  
Article
Improving Encapsulation of Hydrophilic Chloroquine Diphosphate into Biodegradable Nanoparticles: A Promising Approach against Herpes Virus Simplex-1 Infection
by Tábata Loíse Cunha Lima, Renata de Carvalho Feitosa, Emanuell Dos Santos-Silva, Alaine Maria Dos Santos-Silva, Emerson Michell da Silva Siqueira, Paula Renata Lima Machado, Alianda Maira Cornélio, Eryvaldo Sócrates Tabosa Do Egito, Matheus de Freitas Fernandes-Pedrosa, Kleber Juvenal Silva Farias and Arnóbio Antônio Da Silva-Júnior
Pharmaceutics 2018, 10(4), 255; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040255 - 03 Dec 2018
Cited by 51 | Viewed by 4815
Abstract
Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) [...] Read more.
Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepared using a modified emulsification-solvent evaporation method. Physicochemical properties of the NP were monitored using dynamic light scattering, atomic force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diameter of <300 nm, zeta potential of −20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque reduction assay revealed greater efficacy for CQ-NP compared to CQ at concentrations equal to or lower than 20 µg mL−1 (p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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28 pages, 11818 KiB  
Article
Densely PEGylated Polybenzofulvene Brushes for Potential Applications in Drug Encapsulation
by Marco Paolino, Giorgio Grisci, Federica Castriconi, Annalisa Reale, Germano Giuliani, Alessandro Donati, Claudia Bonechi, Gianluca Giorgi, Raniero Mendichi, Daniele Piovani, Antonella Caterina Boccia, Maurizio Canetti, Filippo Samperi, Sandro Dattilo, Cinzia Scialabba, Mariano Licciardi, Eugenio Paccagnini, Mariangela Gentile and Andrea Cappelli
Pharmaceutics 2018, 10(4), 234; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040234 - 15 Nov 2018
Cited by 11 | Viewed by 2941
Abstract
The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems. In this paper, two new polybenzofulvene [...] Read more.
The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems. In this paper, two new polybenzofulvene backbones were assembled by spontaneous polymerization of the appropriate benzofulvene monomers (4,6-PO-BF3k and 4’,6-PO-BF3k) bearing two clickable propargyloxy groups in different positions of the 3-phenylindene scaffold. Poly-4,6-PO-BF3k and poly-4’,6-PO-BF3k were grafted with monomethyl oligo(ethylene glycol) (MOEG) to prepare two new polybenzofulvene brushes (i.e., poly-4,6-MOEG-9-TM-BF3k and poly-4’,6-MOEG-9-TM-BF3k) by means of a “grafting onto” approach, that were characterized from the point of view of their macromolecular features, aggregation liability, and in a preliminary evaluation of biocompatibility. The obtained results make these PEGylated polybenzofulvene brushes (PPBFB) derivatives potentially useful as nanocarriers for nanoencapsulation and delivery of drug molecules. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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18 pages, 3673 KiB  
Article
Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity
by Moses Andima, Gabriella Costabile, Lorenz Isert, Albert J. Ndakala, Solomon Derese and Olivia M. Merkel
Pharmaceutics 2018, 10(4), 232; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040232 - 15 Nov 2018
Cited by 34 | Viewed by 6017
Abstract
β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used [...] Read more.
β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of −13.8 ± 1.61 and −23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β-Sit-PEG-PLA nanoparticles. β-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64–53.08 μg/mL compared to the untreated cells. Taken together, encapsulation of β-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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14 pages, 5524 KiB  
Article
The Combined Effects of Co-Culture and Substrate Mechanics on 3D Tumor Spheroid Formation within Microgels Prepared via Flow-Focusing Microfluidic Fabrication
by Dongjin Lee and Chaenyung Cha
Pharmaceutics 2018, 10(4), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040229 - 13 Nov 2018
Cited by 34 | Viewed by 5621
Abstract
Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as well as basic scientific endeavors, as several cell types can efficiently form spheroids by [...] Read more.
Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as well as basic scientific endeavors, as several cell types can efficiently form spheroids by themselves in both suspension and adherent cell cultures. However, it is more desirable to utilize a 3D scaffold with tunable properties to create more physiologically relevant tumor spheroids as well as optimize their formation. In this study, bioactive spherical microgels supporting 3D cell culture are fabricated by a flow-focusing microfluidic device. Uniform-sized aqueous droplets of gel precursor solution dispersed with cells generated by the microfluidic device are photocrosslinked to fabricate cell-laden microgels. Their mechanical properties are controlled by the concentration of gel-forming polymer. Using breast adenocarcinoma cells, MCF-7, the effect of mechanical properties of microgels on their proliferation and the eventual spheroid formation was explored. Furthermore, the tumor cells are co-cultured with macrophages of fibroblasts, which are known to play a prominent role in tumor physiology, within the microgels to explore their role in spheroid formation. Taken together, the results from this study provide the design strategy for creating tumor spheroids utilizing mechanically-tunable microgels as 3D cell culture platform. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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18 pages, 3098 KiB  
Article
Silk/Fibroin Microcarriers for Mesenchymal Stem Cell Delivery: Optimization of Cell Seeding by the Design of Experiment
by Carlotta Perucca Orfei, Giuseppe Talò, Marco Viganò, Sara Perteghella, Gaia Lugano, Francesca Fabro Fontana, Enrico Ragni, Alessandra Colombini, Paola De Luca, Matteo Moretti, Maria Luisa Torre and Laura De Girolamo
Pharmaceutics 2018, 10(4), 200; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040200 - 24 Oct 2018
Cited by 13 | Viewed by 3590
Abstract
In this methodological paper, lyophilized fibroin-coated alginate microcarriers (LFAMs) proposed as mesenchymal stem cells (MSCs) delivery systems and optimal MSCs seeding conditions for cell adhesion rate and cell arrangement, was defined by a Design of Experiment (DoE) approach. Cells were co-incubated with microcarriers [...] Read more.
In this methodological paper, lyophilized fibroin-coated alginate microcarriers (LFAMs) proposed as mesenchymal stem cells (MSCs) delivery systems and optimal MSCs seeding conditions for cell adhesion rate and cell arrangement, was defined by a Design of Experiment (DoE) approach. Cells were co-incubated with microcarriers in a bioreactor for different time intervals and conditions: variable stirring speed, dynamic culture intermittent or continuous, and different volumes of cells-LFAMs loaded in the bioreactor. Intermittent dynamic culture resulted as the most determinant parameter; the volume of LFAMs/cells suspension and the speed used for the dynamic culture contributed as well, whereas time was a less influencing parameter. The optimized seeding conditions were: 98 min of incubation time, 12.3 RPM of speed, and 401.5 µL volume of cells-LFAMs suspension cultured with the intermittent dynamic condition. This DoE predicted protocol was then validated on both human Adipose-derived Stem Cells (hASCs) and human Bone Marrow Stem Cells (hBMSCs), revealing a good cell adhesion rate on the surface of the carriers. In conclusion, microcarriers can be used as cell delivery systems at the target site (by injection or arthroscopic technique), to maintain MSCs and their activity at the injured site for regenerative medicine. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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15 pages, 3171 KiB  
Article
Strategies to Obtain Encapsulation and Controlled Release of Pentamidine in Mesoporous Silica Nanoparticles
by Enrico Peretti, Ivana Miletto, Barbara Stella, Flavio Rocco, Gloria Berlier and Silvia Arpicco
Pharmaceutics 2018, 10(4), 195; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040195 - 19 Oct 2018
Cited by 22 | Viewed by 3681
Abstract
Pentamidine (PTM), an antiprotozoal agent used in clinics as pentamidine isethionate salt (PTM-S), recently showed high potential also for the treatment of cancer and myotonic dystrophy type I. However, a severe limit to the systemic administration of PTM is represented by its nephrotoxicity, [...] Read more.
Pentamidine (PTM), an antiprotozoal agent used in clinics as pentamidine isethionate salt (PTM-S), recently showed high potential also for the treatment of cancer and myotonic dystrophy type I. However, a severe limit to the systemic administration of PTM is represented by its nephrotoxicity, leading to the need for a system able to achieve a controlled release of the drug. In this study, mesoporous silica nanoparticles (MSNs) were employed for the first time to encapsulate PTM. PTM-S was first used for loading experiments into bare (MSN-OH) and aminopropyl, cyanopropyl and carboxypropyl-functionalized MSNs (MSN-NH2, MSN-CN and MSN-COOH respectively) but it was not adequately loaded in any MSNs. The free base of PTM (PTM-B) was then obtained from PTM-S and successfully loaded into MSNs. Specifically, MSN-COOH exhibited the highest loading capacity. In vitro evaluation of PTM-B kinetic release from the different MSNs was carried out. An influence of the functional groups in slowing the release of the drug, when compared to bare MSNs was observed. Altogether, these results demonstrate that MSN-COOH could be a promising system to achieve a controlled release of PTM. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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21 pages, 3325 KiB  
Article
Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)-Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting Injectable Formulations
by Stavroula Nanaki, Panagiotis Barmpalexis, Alexandros Iatrou, Evi Christodoulou, Margaritis Kostoglou and Dimitrios N. Bikiaris
Pharmaceutics 2018, 10(3), 130; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030130 - 13 Aug 2018
Cited by 42 | Viewed by 5795
Abstract
The present study evaluates the preparation of risperidone controlled release microspheres as appropriate long-acting injectable formulations based on a series of novel biodegradable and biocompatible poly(lactic acid)–poly(propylene adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two-stage melt polycondensation method (esterification and [...] Read more.
The present study evaluates the preparation of risperidone controlled release microspheres as appropriate long-acting injectable formulations based on a series of novel biodegradable and biocompatible poly(lactic acid)–poly(propylene adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two-stage melt polycondensation method (esterification and polycondensation) and characterized by 1H-NMR, differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD) analyses. DSC and XRD results for PLA/PPAd blends (prepared by the solvent evaporation method) showed that these are immiscible, while enzymatic hydrolysis studies performed at 37 °C showed increased mass loss for PPAd compared to PLA. Risperidone-polyester microparticles prepared by the oil–water emulsification/solvent evaporation method showed smooth spherical surface with particle sizes from 1 to 15 μm. DSC, XRD, and Fourier-transformed infrared (FTIR) analyses showed that the active pharmaceutical ingredient (API) was dispersed in the amorphous phase within the polymer matrices, whereas in vitro drug release studies showed risperidone controlled release rates in all PLA/PPAd blend formulations. Finally, statistical moment analysis showed that polyester hydrolysis had a major impact on API release kinetics, while in PLA/PPAd blends with high PLA content, drug release was mainly controlled by diffusion. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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14 pages, 3390 KiB  
Article
A Micellar-Hydrogel Nanogrid from a UV Crosslinked Inulin Derivative for the Simultaneous Delivery of Hydrophobic and Hydrophilic Drugs
by Delia Mandracchia, Adriana Trapani, Sara Perteghella, Cinzia Di Franco, Maria Luisa Torre, Enrica Calleri and Giuseppe Tripodo
Pharmaceutics 2018, 10(3), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030097 - 19 Jul 2018
Cited by 10 | Viewed by 4453
Abstract
Hydrogels are among the most common materials used in drug delivery, as polymeric micelles are too. They, preferentially, load hydrophilic and hydrophobic drugs, respectively. In this paper, we thought to combine the favorable behaviors of both hydrogels and polymeric micelles with the specific [...] Read more.
Hydrogels are among the most common materials used in drug delivery, as polymeric micelles are too. They, preferentially, load hydrophilic and hydrophobic drugs, respectively. In this paper, we thought to combine the favorable behaviors of both hydrogels and polymeric micelles with the specific aim of delivering hydrophilic and hydrophobic drugs for dual delivery in combination therapy, in particular for colon drug delivery. Thus, we developed a hydrogel by UV crosslinking of a methacrylated (MA) amphiphilic derivative from inulin (INU) (as known INU is specifically degraded into the colon) and vitamin E (VITE), called INVITEMA. The methacrylated micelles were physicochemically characterized and subjected to UV irradiation to form what we called the “nanogrids”. The INVITEMA nanogrids were characterized by DSC, SEM, TEM, water uptake and beclomethasone dipropionate (BDP) release. In particular, the release of the hydrophobic drug was specifically assessed to verify that it can spread along the hydrophilic portions and, therefore, effectively released. These systems can open new pharmaceutical applications for known hydrogels or micelle systems, considering that in literature only few examples are present. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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Review

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17 pages, 3116 KiB  
Review
Microencapsulation and Nanoencapsulation Using Supercritical Fluid (SCF) Techniques
by Soon Hong Soh and Lai Yeng Lee
Pharmaceutics 2019, 11(1), 21; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11010021 - 05 Jan 2019
Cited by 91 | Viewed by 14195
Abstract
The unique properties of supercritical fluids, in particular supercritical carbon dioxide (CO2), provide numerous opportunities for the development of processes for pharmaceutical applications. One of the potential applications for pharmaceuticals includes microencapsulation and nanoencapsulation for drug delivery purposes. Supercritical CO2 [...] Read more.
The unique properties of supercritical fluids, in particular supercritical carbon dioxide (CO2), provide numerous opportunities for the development of processes for pharmaceutical applications. One of the potential applications for pharmaceuticals includes microencapsulation and nanoencapsulation for drug delivery purposes. Supercritical CO2 processes allow the design and control of particle size, as well as drug loading by utilizing the tunable properties of supercritical CO2 at different operating conditions (flow ratio, temperature, pressures, etc.). This review aims to provide a comprehensive overview of the processes and techniques using supercritical fluid processing based on the supercritical properties, the role of supercritical carbon dioxide during the process, and the mechanism of formulation production for each process discussed. The considerations for equipment configurations to achieve the various processes described and the mechanisms behind the representative processes such as RESS (rapid expansion of supercritical solutions), SAS (supercritical antisolvent), SFEE (supercritical fluid extraction of emulsions), PGSS (particles from gas-saturated solutions), drying, and polymer foaming will be explained via schematic representation. More recent developments such as fluidized bed coating using supercritical CO2 as the fluidizing and drying medium, the supercritical CO2 spray drying of aqueous solutions, as well as the production of microporous drug releasing devices via foaming, will be highlighted in this review. Development and strategies to control and optimize the particle morphology, drug loading, and yield from the major processes will also be discussed. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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21 pages, 3385 KiB  
Review
Cyclodextrin-Based Metal-Organic Frameworks (CD-MOFs) in Pharmaceutics and Biomedicine
by Yaoyao Han, Weicong Liu, Jianjing Huang, Shuowen Qiu, Huarui Zhong, Dong Liu and Jianqiang Liu
Pharmaceutics 2018, 10(4), 271; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040271 - 12 Dec 2018
Cited by 100 | Viewed by 10792
Abstract
Metal-organic frameworks (MOFs) show promising application in biomedicine and pharmaceutics owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, MOFs are prepared from non-renewable or toxic materials, which limit their real-world applications. Cyclodextrins (CDs) are a [...] Read more.
Metal-organic frameworks (MOFs) show promising application in biomedicine and pharmaceutics owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, MOFs are prepared from non-renewable or toxic materials, which limit their real-world applications. Cyclodextrins (CDs) are a typical natural and biodegradable cyclic oligosaccharide and are primarily used to enhance the aqueous solubility, safety, and bioavailability of drugs by virtue of its low toxicity and highly flexible structure, offering a peculiar ability to form CD/drug inclusions. A sophisticated strategy where CD is deployed as a ligand to form an assembly of cyclodextrin-based MOFs (CD-MOFs) may overcome real-world application drawbacks of MOFs. CD-MOFs incorporate the porous features of MOFs and the encapsulation capability of CD for drug molecules, leading to outstanding properties when compared with traditional hybrid materials. This review focuses on the inclusion technology and drug delivery properties associated with CD-MOFs. In addition, synthetic strategies and currently developed uses of CD-MOFs are highlighted as well. Also, perspectives and future challenges in this rapidly developing research area are discussed. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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23 pages, 1741 KiB  
Review
The Microfluidic Technique and the Manufacturing of Polysaccharide Nanoparticles
by Enrica Chiesa, Rossella Dorati, Silvia Pisani, Bice Conti, Gloria Bergamini, Tiziana Modena and Ida Genta
Pharmaceutics 2018, 10(4), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040267 - 09 Dec 2018
Cited by 70 | Viewed by 5995
Abstract
The microfluidic technique has emerged as a promising tool to accelerate the clinical translation of nanoparticles, and its application affects several aspects, such as the production of nanoparticles and the in vitro characterization in the microenvironment, mimicking in vivo conditions. This review covers [...] Read more.
The microfluidic technique has emerged as a promising tool to accelerate the clinical translation of nanoparticles, and its application affects several aspects, such as the production of nanoparticles and the in vitro characterization in the microenvironment, mimicking in vivo conditions. This review covers the general aspects of the microfluidic technique and its application in several fields, such as the synthesis, recovering, and samples analysis of nanoparticles, and in vitro characterization and their in vivo application. Among these, advantages in the production of polymeric nanoparticles in a well-controlled, reproducible, and high-throughput manner have been highlighted, and detailed descriptions of microfluidic devices broadly used for the synthesis of polysaccharide nanoparticles have been provided. These nanoparticulate systems have drawn attention as drug delivery vehicles over many years; nevertheless, their synthesis using the microfluidic technique is still largely unexplored. This review deals with the use of the microfluidic technique for the synthesis of polysaccharide nanoparticles; evaluating features of the most studied polysaccharide drug carriers, such as chitosan, hyaluronic acid, and alginate polymers. The critical assessment of the most recent research published in literature allows us to assume that microfluidics will play an important role in the discovery and clinical translation of nanoplatforms. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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40 pages, 2480 KiB  
Review
Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery
by Sophia G. Antimisiaris, Spyridon Mourtas and Antonia Marazioti
Pharmaceutics 2018, 10(4), 218; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040218 - 06 Nov 2018
Cited by 406 | Viewed by 18786
Abstract
The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here, we provide [...] Read more.
The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here, we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges which have been identified to date in this field are summarized. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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19 pages, 1840 KiB  
Review
Complex Polymeric Architectures Self-Assembling in Unimolecular Micelles: Preparation, Characterization and Drug Nanoencapsulation
by Stefania Ordanini and Francesco Cellesi
Pharmaceutics 2018, 10(4), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10040209 - 01 Nov 2018
Cited by 33 | Viewed by 4671
Abstract
Unimolecular polymeric micelles are a class of single-molecule amphiphilic core-shell polymeric architectures, where the hydrophobic core is well stabilized by the hydrophilic shell, avoiding intermolecular core-core interactions. Multi-arm copolymers with a dendritic core, as well as hyperbranched and comb-like polymers, can form unimolecular [...] Read more.
Unimolecular polymeric micelles are a class of single-molecule amphiphilic core-shell polymeric architectures, where the hydrophobic core is well stabilized by the hydrophilic shell, avoiding intermolecular core-core interactions. Multi-arm copolymers with a dendritic core, as well as hyperbranched and comb-like polymers, can form unimolecular micelles easily. In this review, examples of polymers able to form detectable unimolecular micelles will be presented, summarizing the analytical techniques used to characterize the unimolecular micelles and discriminate them from other supramolecular aggregates, such as multi-micelle aggregates. Unimolecular micelles are suitable for the nanoencapsulation of guest molecules. Compared to traditional supramolecular micelles, unimolecular micelles do not disassemble under dilution and are stable to environmental modifications. Recent examples of their application as drug delivery systems, endowed with increased stability and transport properties, will be discussed. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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23 pages, 3825 KiB  
Review
Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging
by Silvia Franzé, Francesca Selmin, Elena Samaritani, Paola Minghetti and Francesco Cilurzo
Pharmaceutics 2018, 10(3), 139; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030139 - 28 Aug 2018
Cited by 146 | Viewed by 10623
Abstract
Nowadays, the freeze-drying of liposome dispersions is still necessary to provide a solid dosage form intended for different routes of administration (i.e., parenteral, oral, nasal and/or pulmonary). However, after decades of studies the optimization of process conditions remains still challenging since the freezing [...] Read more.
Nowadays, the freeze-drying of liposome dispersions is still necessary to provide a solid dosage form intended for different routes of administration (i.e., parenteral, oral, nasal and/or pulmonary). However, after decades of studies the optimization of process conditions remains still challenging since the freezing and the dehydration destabilize the vesicle organization with the concomitant drug leakage. Starting from the thermal properties of phospholipids, this work reviews the main formulation and process parameters which can guarantee a product with suitable characteristics and increase the efficiency of the manufacturing process. In particular, an overview of the cryo- and/or lyo-protective mechanisms of several excipients and the possible use of co-solvent mixtures is provided. Attention is also focused on the imaging methods recently proposed to characterize the appearance of freeze-dried products and liposome dispersions upon reconstitution. The combination of such data would allow a better knowledge of the factors causing inter-vials variability in the attempt to improve the quality of the final medicinal product. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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17 pages, 1887 KiB  
Review
Stimuli Responsive Polymeric Systems for Cancer Therapy
by Ali Alsuraifi, Anthony Curtis, Dimitrios A. Lamprou and Clare Hoskins
Pharmaceutics 2018, 10(3), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics10030136 - 22 Aug 2018
Cited by 48 | Viewed by 5305
Abstract
Nanoscale polymers systems have dominated the revolution of drug delivery advancement. Their potential in the fight against cancer is unrivalled with other technologies. Their functionality increase, targeting ability and stimuli responsive nature have led to a major boom in research focus. This review [...] Read more.
Nanoscale polymers systems have dominated the revolution of drug delivery advancement. Their potential in the fight against cancer is unrivalled with other technologies. Their functionality increase, targeting ability and stimuli responsive nature have led to a major boom in research focus. This review article concentrates on the use of these smart polymers in cancer therapy. Nanotechnologies have shown potential as drug carriers leading to increased drug efficacy and penetration. Multifunctional smart carriers which can release their payload upon an external or internal trigger such as pH or temperature are proving to be major frontrunners in the development of effective strategies to overcome this disease with minimal patient side effects. Full article
(This article belongs to the Special Issue Micro and Nano Encapsulation Techniques)
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