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Application Progress of Liposomes in Drug Development

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (12 May 2022) | Viewed by 14645

Special Issue Editor


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Guest Editor
FP-I3ID (Instituto de Investigação, Inovação e Desenvolvimento Fernando Pessoa), FP-BHS (Biomedical and Health Sciences), Universidade Fernando Pessoa, Praça 9 de Abril, 349, 4249-004 Porto, Portugal
Interests: liposomes; membrane interactions; topical vehicles
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Special Issue Information

Dear Colleagues,

Liposomes are a field of intense research, with new developments in the field emerging each year. In the last few years, significant attention has been focused on this subject and noteworthy progress has been made, especially in using liposomes as site-specific drug-delivery systems. These lipid-based nanocarriers have the capacity to improve the retention and release of pharmacologically active compounds at the sites of action, minimizing the associated systemic side effects; they can also be used for the topical administration of drugs, improving penetration through the skin. Their characteristics of biocompatibility and physicochemical stability promote their potential for use as drug-delivery systems, increasing drug stability and bioavailability. Liposomes can also be used as cell models in drug development, for the study of the interaction and partition of drugs with biomembranes.

Authors are kindly invited to submit original papers, communications, and reviews regarding the potential applications of different types of liposomes in Drug Development and Drug-Delivery Systems, to be published in this Issue of the International Journal of Molecular  Sciences.

Dr. Carla Matos
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • drug-delivery systems
  • membrane interactions
  • drug development
  • biocompatible

Published Papers (6 papers)

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Editorial

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3 pages, 178 KiB  
Editorial
Liposomes: The Brave Old World
by Carla M. Matos
Int. J. Mol. Sci. 2023, 24(5), 4343; https://doi.org/10.3390/ijms24054343 - 22 Feb 2023
Viewed by 723
Abstract
Liposomes have been known of for about 60 years, since they were discovered by A [...] Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)

Research

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17 pages, 6196 KiB  
Article
Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta
by Louise Fliedel, Khair Alhareth, Johanne Seguin, Marwa El-Khashab, Audrey Chissey, Nathalie Mignet, Thierry Fournier and Karine Andrieux
Int. J. Mol. Sci. 2022, 23(11), 6299; https://doi.org/10.3390/ijms23116299 - 4 Jun 2022
Cited by 2 | Viewed by 1880
Abstract
Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction [...] Read more.
Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design. Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)
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16 pages, 2461 KiB  
Article
A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease
by Julie Zimmermann, Signe Tandrup Schmidt, Ramona Trebbien, Rebecca Jane Cox, Fan Zhou, Frank Follmann, Gabriel Kristian Pedersen and Dennis Christensen
Int. J. Mol. Sci. 2022, 23(3), 1850; https://doi.org/10.3390/ijms23031850 - 6 Feb 2022
Cited by 4 | Viewed by 2599
Abstract
The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the [...] Read more.
The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective. Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)
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16 pages, 11425 KiB  
Article
Liposomal Formulation of a PLA2-Sensitive Phospholipid–Allocolchicinoid Conjugate: Stability and Activity Studies In Vitro
by Maria K. Kobanenko, Daria S. Tretiakova, Ekaterina S. Shchegravina, Nadezhda V. Antipova, Ivan A. Boldyrev, Alexey Yu. Fedorov, Elena L. Vodovozova and Natalia R. Onishchenko
Int. J. Mol. Sci. 2022, 23(3), 1034; https://doi.org/10.3390/ijms23031034 - 18 Jan 2022
Cited by 8 | Viewed by 1948
Abstract
To assess the stability and efficiency of liposomes carrying a phospholipase A2-sensitive phospholipid-allocolchicinoid conjugate (aC-PC) in the bilayer, egg phosphatidylcholine and 1-palmitoyl-2-oleoylphosphatidylglycerol-based formulations were tested in plasma protein binding, tubulin polymerization inhibition, and cytotoxicity assays. Liposomes L-aC-PC10 containing 10 mol. % aC-PC in [...] Read more.
To assess the stability and efficiency of liposomes carrying a phospholipase A2-sensitive phospholipid-allocolchicinoid conjugate (aC-PC) in the bilayer, egg phosphatidylcholine and 1-palmitoyl-2-oleoylphosphatidylglycerol-based formulations were tested in plasma protein binding, tubulin polymerization inhibition, and cytotoxicity assays. Liposomes L-aC-PC10 containing 10 mol. % aC-PC in the bilayer bound less plasma proteins and were more stable in 50% plasma within 4 h incubation, according to calcein release and FRET-based assays. Liposomes with 25 mol. % of the prodrug (L-aC-PC25) were characterized by higher storage stability judged by their hydrodynamic radius evolution yet enhanced deposition of blood plasma opsonins on their surface according to SDS-PAGE and immunoblotting. Notably, inhibition of tubulin polymerization was found to require that the prodrug should be hydrolyzed to the parent allocolchicinoid. The L-aC-PC10 and L-aC-PC25 formulations demonstrated similar tubulin polymerization inhibition and cytotoxic activities. The L-aC-PC10 formulation should be beneficial for applications requiring liposome accumulation at tumor or inflammation sites. Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)
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20 pages, 2591 KiB  
Article
Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles
by Paulina Skupin-Mrugalska, Philipp A. Elvang and Martin Brandl
Int. J. Mol. Sci. 2021, 22(19), 10456; https://doi.org/10.3390/ijms221910456 - 28 Sep 2021
Cited by 7 | Viewed by 2173
Abstract
Liposome size and in vitro release of the active substance belong to critical quality attributes of liposomal carriers. Here, we apply asymmetric flow field-flow fractionation (AF4) to characterize theranostic liposomes prepared by thin lipid film hydration/extrusion or microfluidics. The vesicles’ size was derived [...] Read more.
Liposome size and in vitro release of the active substance belong to critical quality attributes of liposomal carriers. Here, we apply asymmetric flow field-flow fractionation (AF4) to characterize theranostic liposomes prepared by thin lipid film hydration/extrusion or microfluidics. The vesicles’ size was derived from multi-angle laser light scattering following fractionation (AF4) and compared to sizes derived from dynamic light scattering measurements. Additionally, we adapted a previously developed AF4 method to study zinc phthalocyanine (ZnPc) release/transfer from theranostic liposomes. To this end, theranostic liposomes were incubated with large acceptor liposomes serving as a sink (mimicking biological sinks) and were subsequently separated by AF4. During incubation, ZnPc was transferred from donor to acceptor fraction until reaching equilibrium. The process followed first-order kinetics with half-lives between 119.5–277.3 min, depending on the formulation. The release mechanism was postulated to represent a combination of Fickian diffusion and liposome relaxation. The rate constant of the transfer was proportional to the liposome size and inversely proportional to the ZnPc/POPC molar ratio. Our results confirm the usefulness of AF4 based method to study in vitro release/transfer of lipophilic payload, which may be useful to estimate the unwanted loss of drug from the liposomal carrier in vivo. Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)
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Review

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15 pages, 464 KiB  
Review
Elastic and Ultradeformable Liposomes for Transdermal Delivery of Active Pharmaceutical Ingredients (APIs)
by Eliana B. Souto, Ana S. Macedo, João Dias-Ferreira, Amanda Cano, Aleksandra Zielińska and Carla M. Matos
Int. J. Mol. Sci. 2021, 22(18), 9743; https://doi.org/10.3390/ijms22189743 - 9 Sep 2021
Cited by 29 | Viewed by 4397
Abstract
Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, [...] Read more.
Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their extent/mechanisms of permeation/penetration. In vivo bioavailability of an API administered in the form of ultra-deformable liposomes is similar to the bioavailability achieved when the same API is administered in the form of a solution by subcutaneous or epi-cutaneous injection, which demonstrates their applicability in transdermal drug delivery. Full article
(This article belongs to the Special Issue Application Progress of Liposomes in Drug Development)
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