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Liposomes as Drug Carriers
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Liposomes as Drug Carriers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (10 January 2018) | Viewed by 30351

Special Issue Editors

Prof. Dr. Sophia G. Antimisiaris

E-Mail Website
Guest Editor
1. Laboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rio-Patras, Greece
2. Institute for Chemical Engineering Sciences, Foundation for Research and Technology Hellas, FORTH/ICE-HT, Stadiou Street, 26510 Platani-Rio, Greece
Interests: targeted drug delivery; nanomedicines; liposome technology; lipid-based formulations
Special Issues, Collections and Topics in MDPI journals
Dr. Spyridon Mourtas

E-Mail Website
Guest Editor
1. Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, 26510 Rio-Patras, Greece
2. Institute for Chemical Engineering Sciences, Foundation for Research and Technology Hellas, FORTH/ICE-HT, Stadiou Street, 26504 Platani-Rio, Greece
Interests: targeted drug delivery; nanoliposomes; organic chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liposomes are broadly used as nanocarriers for controlled delivery/ targeting of drugs. Indeed, liposomal formulations may have an important impact on the therapeutic potential of active substances, just by providing the means to protect them from hostile environments in the biological milieu, and/or by increasing their retention at sites of administration or action, increasing, thus, their topical bioavailability.

Furthermore, due to their exceptional physicochemical characteristics, including their small size (at nanoscale), biological compatibility, versatility (which allows easy surface modification) and capability to encapsulate/incorporate high amounts of almost any type of active molecule, they are on the top of the list when challenging drug delivery applications are under consideration. Examples of the later include early diagnosis and/or therapy of neurodegenerative diseases (Alzheimer’s disease, Parkinson’s, Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), etc.), were delivery of drugs to the brain is impeded by the blood brain barrier; as well as realization of the therapeutic potential of oligonucleotides, were the physicochemical properties of the actives and their substantial susceptibility to degrading enzymes are major obstacles. A number of technologies which enable surface modification of liposomes (using different types of ligands, such as peptides, antibodies, small organic molecules, aptamers, etc.), by gentle organic-synthesis protocols, have led to the formation of actively- targeted functionalized vesicles with increased affinity for specific biological targets or barriers. The exploitation of biological approaches to overcome barriers, such as those used by bacteria and viruses, and more recently the organotropism of extracellular vesicles, have also been considered for the construction of bio-inspired liposomes, with increased targeting capability. This Special Issue is aimed at covering all the different approaches of liposome diagnostic/therapeutic applications, with specific examples from recent projects.

Prof. Sophia G. Antimisiaris
Dr. Spyridon Mourtas
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • liposomes
  • nanocarriers
  • controlled release
  • retention
  • bioavailability
  • active targeting
  • surface modification
  • exosomes
  • cellular vesicles

Published Papers (5 papers)

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Research

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9 pages, 1414 KiB  
Communication
Liposomes as Gene Delivery Vectors for Human Placental Cells
by Lucie Valero, Khair Alhareth, Jenifer Espinoza Romero, Warren Viricel, Jeanne Leblond, Audrey Chissey, Hélène Dhotel, Caroline Roques, Danielle Campiol Arruda, Virginie Escriou, Nathalie Mignet, Thierry Fournier and Karine Andrieux
Molecules 2018, 23(5), 1085; https://doi.org/10.3390/molecules23051085 - 04 May 2018
Cited by 21 | Viewed by 5122
Abstract
Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations [...] Read more.
Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 ± 15% and 44 ± 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 ± 5%) and CSL-3 (22 ± 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients. Full article
(This article belongs to the Special Issue Liposomes as Drug Carriers)
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18 pages, 2244 KiB  
Article
Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach
by Emiliano Laudadio, Cristina Minnelli, Adolfo Amici, Luca Massaccesi, Giovanna Mobbili and Roberta Galeazzi
Molecules 2018, 23(2), 441; https://doi.org/10.3390/molecules23020441 - 16 Feb 2018
Cited by 22 | Viewed by 4021
Abstract
As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the [...] Read more.
As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in the presence of Ca2+ and Mg2+ divalent salts. Experimental and in silico results show a very high correlation, thus confirming the efficiency of the developed methodology. In particular, we found out that the presence of calcium ions hinders the insertion of EGCG in the liposome bilayer in both neutral and anionic systems. On the contrary, the presence of MgCl2 improves the insertion degree of EGCG molecules respect to the liposomes without divalent salts. The best and most efficient salt concentration is that corresponding to a 5:1 molar ratio between Mg2+ and EGCG, in both neutral and anionic vesicles. Concerning the lipid matrix composition, the anionic one results in better promotion of the catechin insertion within the bilayer since experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic liposomal formulation with magnesium chloride, avoids time-consuming separation steps of unentrapped active principle and appears particularly suitable for EGCG delivery applications. Full article
(This article belongs to the Special Issue Liposomes as Drug Carriers)
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15 pages, 3863 KiB  
Article
Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells
by Xianchun Wen, Jiping Li, Defu Cai, Liling Yue, Qi Wang, Li Zhou, Li Fan, Jianwen Sun and Yonghui Wu
Molecules 2018, 23(2), 268; https://doi.org/10.3390/molecules23020268 - 29 Jan 2018
Cited by 40 | Viewed by 5386
Abstract
Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical [...] Read more.
Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the αvβ3-positive MDA-MB-231 cells. Besides exhibiting greater cytotoxicity in vitro, compared with non-targeted shikonin-loaded liposomes (SSLs-SHK), RGD-SSLs-SHK could also evidently induce apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. It could also inhibit cell proliferation, migration, invasion, and adhesion by reducing the expression of MMP-9 and the level of NF-κB p65, but did not affect the expression of MMP-2 in the MDA-MB-231 cells. Therefore, these findings indicated that the strategy to use RGD-modified liposomes as carriers for targeted delivery of shikonin is a very promising approach to achieve breast cancer targeted therapy. Full article
(This article belongs to the Special Issue Liposomes as Drug Carriers)
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17 pages, 3336 KiB  
Article
The Impact of Lipid Types and Liposomal Formulations on Osteoblast Adiposity and Mineralization
by Shun-Fu Chang, Chih-Chang Yeh, Pin-Jyun Chen and Hsin-I Chang
Molecules 2018, 23(1), 95; https://doi.org/10.3390/molecules23010095 - 02 Jan 2018
Cited by 12 | Viewed by 4484
Abstract
Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while [...] Read more.
Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Lipids are common constituents in supramolecular vesicles (e.g., micelles or liposomes) that serve as drug delivery systems. Liposomal formulations such as Meriva® were proven to decrease joint pain and improve joint function in osteoarthritis (OA) patients. In this study, we evaluated how lipid types and liposomal formulations affect osteoblast behavior including cell viability, differentiation, mineralization and inflammation. Various liposomal formulations were prepared using different types of lipids, including phosphatidylcholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE), cholesterol (Chol), 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol HCl), and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) to investigate the impact on osteoblast differentiation and inflammation. The results indicated that cationic lipids, DC-cholesterol and DOTAP, presented higher dose-dependent cytotoxicity and caused high level of inflammatory responses. Due to the natural properties of lipids, all the lipids can induce lipid droplet formation in osteoblasts but the level of lipid droplet accumulation was different. In comparison with cationic lipids, neutral lipids induced less adiposity, and maintained high osteoblast mineralization. Similar to previous researches, we also confirmed an inverse relationship between lipid droplet formation and osteoblast mineralization in 7F2 mouse osteoblasts. Importantly, PC containing liposomes (PC only and PC/DOTAP) suppressed IL-1β-induced gene expression of COX-2 and MMP-3 but not Chol/DOTAP liposomes or DC-Chol/DOPE liposomes. Taken together, we suggested that PC contained liposomes could provide the best liposomal formulation for the treatment of bone diseases. Full article
(This article belongs to the Special Issue Liposomes as Drug Carriers)
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Review

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17 pages, 466 KiB  
Review
Liposomes: Clinical Applications and Potential for Image-Guided Drug Delivery
by Narottam Lamichhane, Thirupandiyur S. Udayakumar, Warren D. D’Souza, Charles B. Simone II, Srinivasa R. Raghavan, Jerimy Polf and Javed Mahmood
Molecules 2018, 23(2), 288; https://doi.org/10.3390/molecules23020288 - 30 Jan 2018
Cited by 187 | Viewed by 10375
Abstract
Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of [...] Read more.
Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties. Full article
(This article belongs to the Special Issue Liposomes as Drug Carriers)
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