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Pharmaceutics
Special Issues
Targeted Liposomal Drug Delivery
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Targeted Liposomal Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 July 2022) | Viewed by 19353

Special Issue Editors

Prof. Dr. Marlus Chorilli

E-Mail Website
Guest Editor
Departament of Drugs and Medicines, São Paulo State University—UNESP, Rodovia Araraquara Jaú, km. 1, 14800-903 Araraquara, São Paulo, Brazil
Interests: mucoadhesion; targeted delivery; lipid-based nanocarriers; drug delivery systems; polymeric systems; nanotechnology
Special Issues, Collections and Topics in MDPI journals
Dr. Marcela Tavares Luiz

E-Mail Website
Guest Editor
Department of Drugs and Medicines, São Paulo State University—UNESP, Rodovia Araraquara Jaú, Km. 1, Araraquara 14800-903, SP, Brazil
Interests: polymeric nanocapsules; hybrid nanoparticles; cyclic anhydride copolymers; hydrogels; controlled and targeted drug delivery; in vitro biological testing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liposomes at the top of the list of nanocarriers used to deliver therapeutic agents (e.g., chemotherapeutics, nucleic acid, peptides) for improving the effectiveness and safety of therapies. The wide application of liposomal formulations in the pharmaceutical field is related to their excellent physicochemical characteristics, including their capacity to encapsulate high amounts of both lipophilic and hydrophilic molecules, small particle size, biocompatibility, and biodegradability. Furthermore, liposomes are versatile vesicles, which allow the modification of their surfaces with ligands that show high affinity and specificity to the target tissue. As a result, the active targeting of liposomes can potentialize the therapeutic effect of drugs and reduce their side effects.

Recognizing the importance of liposomes in the pharmaceutical field, we would like to invite you to contribute a short communication, research article, or review article to this issue, entitled “Targeted Liposomal Drug Delivery”. This Special Issue will publish articles describing the design, development, and characterization of ligand-targeted liposomes for the active targeting of therapeutic agents.

Prof. Dr. Marlus Chorilli
Dr. Marcela Tavares Luiz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • active targeting
  • drug delivery systems
  • lipid-based nanocarriers
  • liposomes
  • targeted-delivery

Published Papers (6 papers)

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Research

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14 pages, 6388 KiB  
Article
Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions
by Lauren B. Grimsley, Phillip C. West, Callie D. McAdams, Charles A. Bush, Stacy S. Kirkpatrick, Joshua D. Arnold, Michael R. Buckley, Raymond A. Dieter III, Michael B. Freeman, Michael M. McNally, Scott L. Stevens, Oscar H. Grandas and Deidra J. H. Mountain
Pharmaceutics 2021, 13(11), 1816; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111816 - 31 Oct 2021
Cited by 2 | Viewed by 2032
Abstract
Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we [...] Read more.
Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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18 pages, 2581 KiB  
Article
Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
by Lewis J. Renshall, Frances Beards, Angelos Evangelinos, Susan L. Greenwood, Paul Brownbill, Adam Stevens, Colin P. Sibley, John D. Aplin, Edward D. Johnstone, Tambet Teesalu and Lynda K. Harris
Pharmaceutics 2021, 13(11), 1778; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111778 - 25 Oct 2021
Cited by 11 | Viewed by 3112
Abstract
Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus [...] Read more.
Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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15 pages, 3861 KiB  
Article
Targeted Delivery of Liposomal Temozolomide Enhanced Anti-Glioblastoma Efficacy through Ultrasound-Mediated Blood–Brain Barrier Opening
by Zhuqing Song, Xiuxian Huang, Jieqiong Wang, Feiyan Cai, Ping Zhao and Fei Yan
Pharmaceutics 2021, 13(8), 1270; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081270 - 17 Aug 2021
Cited by 19 | Viewed by 2424
Abstract
Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of [...] Read more.
Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of the blood–brain barrier (BBB), which greatly limits the availability of therapeutic drugs to the tumor. Ultrasound-mediated BBB opening provides a promising approach to help deliver drugs to brain tumors. The use of temozolomide (TMZ) in the clinical treatment of GBM has been shown to be able to increase survival in patients with GBM, but this improvement is still trivial. In this study, we developed a liposomal temozolomide formulation (TMZ-lipo) and locally delivered these nanoparticles into GBM through ultrasound-mediated BBB opening technology, significantly suppressing tumor growth and prolonging tumor-bearing animal survival. No significant side effects were observed in comparison with control rats. Our study provides a novel strategy to improve the efficacy of TMZ against GBM. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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19 pages, 3112 KiB  
Article
Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion
by Xudong Tang, Qiaoru Dong, Jun Li, Fang Li, Bozena B. Michniak-Kohn, Denggao Zhao, Chi-Tang Ho and Qingrong Huang
Pharmaceutics 2021, 13(8), 1185; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081185 - 31 Jul 2021
Cited by 14 | Viewed by 3384
Abstract
Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study [...] Read more.
Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study the impact of THC on the melanogenic process under stressed conditions. It was demonstrated that THC could effectively inhibit the α-MSH (melanocyte-stimulating hormone) induced melanin production in B16F10 melanoma cells and the expressions of three key enzymes involved with the biosynthetic process of melanin, tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), were all significantly reduced. In addition, an in vitro human keratinocyte cell model was used to investigate the potential protective role of THC on H2O2-induced cytotoxicity. It was found that THC could prevent H2O2-induced oxidative stress based on the results of both the cell viability study and the intracellular ROS (reactive oxygen species) study assessed by the flow cytometry. Last, THC was formulated into a lecithin based nanoemulsion, and an in vitro Franz diffusion cell study using Strat-M® membrane concluded that the nanoemulsion could significantly enhance the membrane permeation compared to the unformatted THC suspension. This research demonstrated the anti-melanogenic benefits of THC on the melanoma and keratinocyte cell models and the topical delivery efficacy could be significantly enhanced using a lecithin based nanoemulsion. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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Review

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31 pages, 3038 KiB  
Review
Targeted Liposomes: A Nonviral Gene Delivery System for Cancer Therapy
by Marcela Tavares Luiz, Jessyca Aparecida Paes Dutra, Larissa Bueno Tofani, Jennifer Thayanne Cavalcante de Araújo, Leonardo Delello Di Filippo, Juliana Maldonado Marchetti and Marlus Chorilli
Pharmaceutics 2022, 14(4), 821; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040821 - 08 Apr 2022
Cited by 29 | Viewed by 3672
Abstract
Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy [...] Read more.
Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy has been a potential therapeutic approach owing to its ability to introduce, silence, or change the content of the human genetic code for inhibiting tumor progression, angiogenesis, and metastasis. For the proper delivery of genes to tumor cells, it requires the use of gene vectors for protecting the therapeutic gene and transporting it into cells. Among these vectors, liposomes have been the nonviral vector most used because of their low immunogenicity and low toxicity. Furthermore, this nanosystem can have its surface modified with ligands (e.g., antibodies, peptides, aptamers, folic acid, carbohydrates, and others) that can be recognized with high specificity and affinity by receptor overexpressed in tumor cells, increasing the selective delivery of genes to tumors. In this context, the present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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34 pages, 3642 KiB  
Review
Design and Application of Near-Infrared Nanomaterial-Liposome Hybrid Nanocarriers for Cancer Photothermal Therapy
by Pan Liang, Linshen Mao, Yanli Dong, Zhenwen Zhao, Qin Sun, Maryam Mazhar, Yining Ma, Sijin Yang and Wei Ren
Pharmaceutics 2021, 13(12), 2070; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122070 - 03 Dec 2021
Cited by 14 | Viewed by 2968
Abstract
Liposomes are attractive carriers for targeted and controlled drug delivery receiving increasing attention in cancer photothermal therapy. However, the field of creating near-infrared nanomaterial-liposome hybrid nanocarriers (NIRN-Lips) is relatively little understood. The hybrid nanocarriers combine the dual superiority of nanomaterials and liposomes, with [...] Read more.
Liposomes are attractive carriers for targeted and controlled drug delivery receiving increasing attention in cancer photothermal therapy. However, the field of creating near-infrared nanomaterial-liposome hybrid nanocarriers (NIRN-Lips) is relatively little understood. The hybrid nanocarriers combine the dual superiority of nanomaterials and liposomes, with more stable particles, enhanced photoluminescence, higher tumor permeability, better tumor-targeted drug delivery, stimulus-responsive drug release, and thus exhibiting better anti-tumor efficacy. Herein, this review covers the liposomes supported various types of near-infrared nanomaterials, including gold-based nanomaterials, carbon-based nanomaterials, and semiconductor quantum dots. Specifically, the NIRN-Lips are described in terms of their feature, synthesis, and drug-release mechanism. The design considerations of NIRN-Lips are highlighted. Further, we briefly introduced the photothermal conversion mechanism of NIRNs and the cell death mechanism induced by photothermal therapy. Subsequently, we provided a brief conclusion of NIRNs-Lips applied in cancer photothermal therapy. Finally, we discussed a synopsis of associated challenges and future perspectives for the applications of NIRN-Lips in cancer photothermal therapy. Full article
(This article belongs to the Special Issue Targeted Liposomal Drug Delivery)
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