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Phospholipid-Conjugated PEG--PCL Copolymers as Precursors of Micellar Vehicles for Amphotericin B.

作者信息

Arias Elsa R, Angarita-Villamizar Vivian, Baena Yolima, Parra-Giraldo Claudia, Perez Leon D

机构信息

Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia-Sede Bogotá, Carrera 45 N° 26-85, Bogotá 11001, Colombia.

Grupo de Investigación SILICOMOBA, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia-Sede Bogotá, Carrera 30 # 45-03, Bogotá 11001, Colombia.

出版信息

Polymers (Basel). 2021 May 27;13(11):1747. doi: 10.3390/polym13111747.


DOI:10.3390/polym13111747
PMID:34071785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8199447/
Abstract

Amphotericin B (AmB) is a widely used antifungal that presents a broad action spectrum and few reports on the development of resistance. However, AmB is highly toxic, causing renal failure in a considerable number of treated patients. Although when AmB is transported via polymer micelles (PMs) as delivery vehicles its nephrotoxicity has been successfully attenuated, this type of nanoparticle has limitations, such as low encapsulation capacity and poor stability in aqueous media. In this research, the effect of modifying polyethyleglicol--poly(ε-caprolactone) (PEG--PCL) with 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) on the performance of PMs as vehicles for AmB was studied. PEG--PCL with two different lengths of a PCL segment was prepared via ring opening polymerisation and modified with DSPE at a post-synthesis stage through amidation. Upon modification with DSPE, a copolymer was self-assembled, thereby producing particles with hydrodynamic diameters below 100 nm and a lower critical micelle concentration than that of the raw copolymers. Likewise, in the presence of DSPE, the loading capacity of AmB increased because of the formed intermolecular interactions, such as hydrogen bonds, which also caused a lower aggregation of this drug. The assessment of in vitro toxicity against red blood cells indicated that the toxicity of AmB decreased upon encapsulation; however, its antifungal action against clinical yeasts was maintained and enhanced, as indicated by a decrease in its minimum inhibitory concentration.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/70f5e1422465/polymers-13-01747-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/9c2398a22afe/polymers-13-01747-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/ffb67aa04f18/polymers-13-01747-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/af4854692bf1/polymers-13-01747-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/106fc1ceec43/polymers-13-01747-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/a9f2a9d6d421/polymers-13-01747-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/c1e729de0cee/polymers-13-01747-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/e83325f2e371/polymers-13-01747-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/e45932715665/polymers-13-01747-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/70f5e1422465/polymers-13-01747-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/9c2398a22afe/polymers-13-01747-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/ffb67aa04f18/polymers-13-01747-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/af4854692bf1/polymers-13-01747-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/106fc1ceec43/polymers-13-01747-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/a9f2a9d6d421/polymers-13-01747-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/c1e729de0cee/polymers-13-01747-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/e83325f2e371/polymers-13-01747-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/e45932715665/polymers-13-01747-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b81/8199447/70f5e1422465/polymers-13-01747-g007.jpg

相似文献

[1]
Phospholipid-Conjugated PEG--PCL Copolymers as Precursors of Micellar Vehicles for Amphotericin B.

Polymers (Basel). 2021-5-27

[2]
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[5]
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[6]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Recent Applications of Amphiphilic Copolymers in Drug Release Systems for Skin Treatment.

Pharmaceutics. 2024-9-13

[2]
Emerging Polymer-Based Nanosystem Strategies in the Delivery of Antifungal Drugs.

Pharmaceutics. 2023-7-1

[3]
A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery.

Molecules. 2023-3-15

[4]
Smart Polymeric Micelles for Anticancer Hydrophobic Drugs.

Cancers (Basel). 2022-12-20

本文引用的文献

[1]
Amphotericin B loaded ethyl cellulose nanoparticles with magnified oral bioavailability for safe and effective treatment of fungal infection.

Biomed Pharmacother. 2020-8

[2]
Development of Amphotericin B Micellar Formulations Based on Copolymers of Poly(ethylene glycol) and Poly(ε-caprolactone) Conjugated with Retinol.

Pharmaceutics. 2020-2-25

[3]
Reducing the toxicity of amphotericin B by encapsulation using methoxy poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine).

Biomater Sci. 2018-7-24

[4]
Liposomal amphotericin B treatment of Old World cutaneous and mucosal leishmaniasis: A literature review.

Acta Trop. 2018-6

[5]
Nanoprecipitation process: From encapsulation to drug delivery.

Int J Pharm. 2017-8-9

[6]
The global problem of antifungal resistance: prevalence, mechanisms, and management.

Lancet Infect Dis. 2017-7-31

[7]
Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair.

Neural Regen Res. 2017-6

[8]
First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia.

J Infect. 2016-7-21

[9]
Reformulation of Fungizone by PEG-DSPE Micelles: Deaggregation and Detoxification of Amphotericin B.

Pharm Res. 2016-9

[10]
Comparison between liposomal formulations of amphotericin B.

Med Mycol. 2016-3

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