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基于改性壳聚糖和透明质酸混合物的水凝胶作为细胞抑制剂递送的聚合物基质。

Hydrogels on the Base of Modified Chitosan and Hyaluronic Acid Mix as Polymer Matrices for Cytostatics Delivery.

作者信息

Vildanova Regina, Lobov Alexander, Spirikhin Leonid, Kolesov Sergey

机构信息

Ufa Institute of Chemistry, Ufa Federal Research Centre of the Russian Academy of Sciences, 450054 Ufa, Russia.

出版信息

Gels. 2022 Feb 9;8(2):104. doi: 10.3390/gels8020104.

Abstract

The development of biodegradable polysaccharide hydrogel matrices for cytostatic delivery can improve the therapeutic results of patients by prolonging the action of the drug, reducing its toxicity and providing additional biological activity by polysaccharides. In this work, N-succinyl chitosan/hyaluronic acid dialdehyde/cytostatic formulations have been prepared using two different chitosan grades (30 kDa and 150 kDa) and hyaluronic acid dialdehyde. The interaction of amino groups of N-succinyl chitosan and aldehydes of hyaluronic acid resulted in the formation of azomethine bonds and was demonstrated using C NMR. The elastic properties of the obtained hydrogels determine their use as implants. Two cytostatics-5-fluorouracil and mitomycin C were chosen as drugs because of their using both in oncology and in ophthalmology for the surgical treatment of glaucoma. Hydrogel formulations containing cytostatic were prepared and drug release was studied using in vitro dialysis method. It was established that the molecular weight of N-succinyl chitosan and rheological properties of hydrogel influenced the drug release behavior of the gelling delivery system. Formulations prepared from N-succinyl chitosan with greatest molecular weight and mitomycin C were found to be the most promising for medical application due to their rheological properties and prolonged drug release. Mild preparation conditions, simplicity of the technique, short gelation time (within a minute), 100% yield of hydrogel, suitability for drug release applications are the main advantages of the obtained hydrogels.

摘要

用于细胞抑制剂递送的可生物降解多糖水凝胶基质的开发,可通过延长药物作用时间、降低其毒性以及多糖提供的额外生物活性来改善患者的治疗效果。在这项工作中,使用两种不同分子量的壳聚糖(30 kDa和150 kDa)和透明质酸二醛制备了N-琥珀酰壳聚糖/透明质酸二醛/细胞抑制剂制剂。N-琥珀酰壳聚糖的氨基与透明质酸的醛基之间的相互作用导致形成甲亚胺键,并通过碳核磁共振(C NMR)得以证实。所得水凝胶的弹性特性决定了它们可作为植入物使用。选择两种细胞抑制剂——5-氟尿嘧啶和丝裂霉素C作为药物,是因为它们在肿瘤学和眼科青光眼手术治疗中均有应用。制备了含细胞抑制剂的水凝胶制剂,并使用体外透析法研究了药物释放情况。结果表明,N-琥珀酰壳聚糖的分子量和水凝胶的流变学性质影响了凝胶递送系统的药物释放行为。由于其流变学性质和延长的药物释放,由分子量最大的N-琥珀酰壳聚糖和丝裂霉素C制备的制剂被认为在医学应用方面最具前景。温和的制备条件、技术的简易性、较短的凝胶化时间(在一分钟内)、水凝胶100%的产率、适用于药物释放应用是所得水凝胶的主要优点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7d3/8871865/e14e9cb6d760/gels-08-00104-g007.jpg

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