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      Self-Assembly of Amphiphilic Compounds as a Versatile Tool for Construction of Nanoscale Drug Carriers

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          Abstract

          This review focuses on synthetic and natural amphiphilic systems prepared from straight-chain and macrocyclic compounds capable of self-assembly with the formation of nanoscale aggregates of different morphology and their application as drug carriers. Since numerous biological species (lipid membrane, bacterial cell wall, mucous membrane, corneal epithelium, biopolymers, e.g., proteins, nucleic acids) bear negatively charged fragments, much attention is paid to cationic carriers providing high affinity for encapsulated drugs to targeted cells. First part of the review is devoted to self-assembling and functional properties of surfactant systems, with special attention focusing on cationic amphiphiles, including those bearing natural or cleavable fragments. Further, lipid formulations, especially liposomes, are discussed in terms of their fabrication and application for intracellular drug delivery. This section highlights several features of these carriers, including noncovalent modification of lipid formulations by cationic surfactants, pH-responsive properties, endosomal escape, etc. Third part of the review deals with nanocarriers based on macrocyclic compounds, with such important characteristics as mucoadhesive properties emphasized. In this section, different combinations of cyclodextrin platform conjugated with polymers is considered as drug delivery systems with synergetic effect that improves solubility, targeting and biocompatibility of formulations.

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          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            Liposomal drug delivery systems: from concept to clinical applications.

            The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. Copyright © 2012 Elsevier B.V. All rights reserved.
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              Advances and Challenges of Liposome Assisted Drug Delivery

              The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 September 2020
                September 2020
                : 21
                : 18
                : 6961
                Affiliations
                A.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov street 8, Kazan 420088, Russia; ggulnara@ 123456bk.ru (G.G.); nemezc1988@ 123456yandex.ru (D.G.); kuznetsov_denis91@ 123456mail.ru (D.K.); rais.pavlov@ 123456iopc.ru (R.P.); kpetrov2005@ 123456mail.ru (K.P.); lucia@ 123456iopc.ru (L.Z.); oleg@ 123456iopc.ru (O.S.)
                Author notes
                [* ]Correspondence: rusl701@ 123456yandex.ru ; Tel.: +7-(843)-273-22-93; Fax: +7-(843)-273-22-53
                Article
                ijms-21-06961
                10.3390/ijms21186961
                7555343
                32971917
                29839758-3c86-4c8a-95da-0cb40ece6bf3
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 August 2020
                : 19 September 2020
                Categories
                Review

                Molecular biology
                amphiphile,cationic surfactants,drug delivery,liposome,endosomal escape,macrocycle,polymer,mucoadhesion

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