Human plasma-derived exosomal gel: a biomimetic cargo for the transdermal delivery of methotrexate.

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Rabia Gul, Wajeeha Khalid, Muhammad Sarfraz, Yousef A Bin Jardan, Muhammad Ikram, Hamid Bashir, Nadeem Ahmad, Laraib Khan, Bazla Siddiqui, Imran Nazir, Yueshui Jiang, Muhammad Imran Amirzada
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Abstract

The aim of the study was to explore the potential of human plasma-derived exosomal gel as a carrier for transdermal drug delivery. Exosomes were isolated from human plasma through a combination of ultracentrifugation and dialysis techniques. Methotrexate (MTX), a weak acid drug with log P 1.53 (low permeability), was utilised as a model drug. MTX was loaded into exosomes using the freeze-thaw method. MTX-loaded exosomes were incorporated into a gel, employing carbopol 940 as a gelling agent. MTX loaded exosomes exhibited a mean size of 162.15 ± 4.21 nm, a polydispersity index (PDI) 0.372 ± 0.024, and a zeta potential of -30.6 ± 0.71 mV. Exosomal gel displayed good physicochemical properties along with desirable rheological behaviour that eased skin application. MTX-loaded exosomal gel exhibited sustained release of 59.14 ± 0.812% of the drug within 72 h at pH 7.4 as compared to nonexosomal gel p < 0.0001. MTX-loaded exosomal gel demonstrated a three-fold increase in skin permeability as compared to MTX loaded gel. Moreover, results of in-vivo studies on the carrageenan-induced inflammation model indicated exosomal gel and MTX loaded exosomal gel reduced inflammation as compared to MTX gel. These findings suggested the potential of exosomes as an emerging platform for transdermal drug delivery, offering enhanced skin penetration.

人血浆源性外泌体凝胶:用于甲氨蝶呤经皮递送的仿生货物。
本研究的目的是探索人血浆源性外泌体凝胶作为经皮给药载体的潜力。外泌体通过超离心和透析技术的结合从人血浆中分离出来。以logp 1.53(低通透性)的弱酸性药物甲氨蝶呤(MTX)为模型药物。利用冻融法将MTX装载到外泌体中。将携带mtx的外泌体纳入凝胶中,使用卡波波尔940作为胶凝剂。MTX负载的外泌体平均大小为162.15±4.21 nm, PDI为0.372±0.024,zeta电位为-30.6±0.71 mV。外泌体凝胶显示出良好的物理化学性质以及理想的流变学行为,减轻了皮肤应用。与非外泌体凝胶相比,负载MTX的外泌体凝胶在pH 7.4下72小时内的药物缓释量为59.14±0.812%。卡拉胶诱导炎症模型的体内研究表明,与MTX凝胶相比,负载MTX的外泌体凝胶和外泌体凝胶可以减轻炎症。这些发现表明外泌体作为经皮药物递送的新兴平台的潜力,提供增强的皮肤穿透性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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