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水凝胶作为角膜基质替代物用于药物眼部渗透的体外评估。

Hydrogels as Corneal Stroma Substitutes for In Vitro Evaluation of Drug Ocular Permeation.

作者信息

Burgalassi Susi, Zucchetti Erica, Ling Leonardo, Chetoni Patrizia, Tampucci Silvia, Monti Daniela

机构信息

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), 56122 Pisa, Italy.

出版信息

Pharmaceutics. 2022 Apr 13;14(4):850. doi: 10.3390/pharmaceutics14040850.

Abstract

Hydrogels are complex hydrophilic structures, consisting of crosslinked homopolymers or copolymers insoluble in water. Due to their controllable bio-physicochemical properties mimicking the morphology of the native extracellular matrix, they are a key part of a lot of research fields, including medicine, pharmaceutics, and tissue engineering. This paper was focused on the preparation and characterization of hydrogels from different blends of polyvinyl alcohol (PVA) with microcrystalline cellulose (MCC) and gelatin (GEL) at various ratios, and from gelatin and chitosan alone to understand their feasibility of utilizing as corneal stroma substitutes in permeability tests for drug candidate molecules in early stages of their development. The characterization was carried out by differential scanning calorimetry, electron microscopy (SEM), water content, mass loss, water permeability, wettability, and tensile stress-strain tests. After the physicochemical characterization, PVA/MCC blend and chitosan proved to be the most promising constructs, showing negligible mass loss after immersion in aqueous medium for two weeks and low hydrodynamic permeability. They were then employed in drug molecules permeation studies and these data were compared to that obtained through excised tissues. The results obtained showed that PVA/MCC hydrogels have similar mechanical and permeability properties to corneal stroma.

摘要

水凝胶是复杂的亲水性结构,由交联的不溶于水的均聚物或共聚物组成。由于其可控制的生物物理化学性质模拟了天然细胞外基质的形态,它们是许多研究领域的关键部分,包括医学、制药和组织工程。本文重点研究了不同比例的聚乙烯醇(PVA)与微晶纤维素(MCC)和明胶(GEL)的混合物以及单独的明胶和壳聚糖制备水凝胶及其表征,以了解它们在药物候选分子开发早期的通透性测试中用作角膜基质替代物的可行性。通过差示扫描量热法、电子显微镜(SEM)、含水量、质量损失、水渗透性、润湿性和拉伸应力-应变测试进行表征。经过物理化学表征后,PVA/MCC混合物和壳聚糖被证明是最有前景的构建体,在水性介质中浸泡两周后质量损失可忽略不计,且具有低流体动力学渗透性。然后将它们用于药物分子渗透研究,并将这些数据与通过切除组织获得的数据进行比较。所得结果表明,PVA/MCC水凝胶具有与角膜基质相似的机械和渗透性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa4/9027330/a206c2c59642/pharmaceutics-14-00850-g001.jpg

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