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基于甲基丙烯酰化β-环糊精的 pH 响应性共聚网络凝胶用于亲水性和疏水性药物的控制共递送

pH-Responsive Copolymeric Network Gel Using Methacrylated β-Cyclodextrin for Controlled Codelivery of Hydrophilic and Hydrophobic Drugs.

机构信息

Department of Chemistry, Indian Institute of Technology (ISM), Dhanbad 826004, India.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, India.

出版信息

ACS Appl Bio Mater. 2022 Jul 18;5(7):3530-3543. doi: 10.1021/acsabm.2c00473. Epub 2022 Jun 23.

DOI:10.1021/acsabm.2c00473
PMID:35734869
Abstract

In medical science, sometimes two drugs with different solubilities are simultaneously required in combination to treat various diseases. Herein, a pH-responsive, copolymeric, antioxidant, biocompatible, and chemically crosslinked network gel is prepared to explore its capability as a matrix for controlled release of both hydrophobic [ibuprofen (IB)] and hydrophilic [tetracycline hydrochloride (TCH)] drugs, simultaneously. This three-dimensional β-CD-Meth-cl-(PHPMA--PAAc) network hydrogel is synthesized via two steps: (I) methacrylation of β-cyclodextrin and (II) grafting of poly(hydroxypropyl methacrylate) and poly(acrylic acid), followed by crosslinking of poly(ethylene glycol) diacrylate onto the backbone of methacrylated β-cyclodextrin (β-CD-Meth). The successful synthesis of the hydrogel is confirmed using several physiochemical characterizations. The β-CD-Meth-cl-(PHPMA--PAAc) hydrogel has an excellent network-like surface morphology. The potential pH-responsive high swelling behavior and excellent shrinking features suggest the reversible nature of the synthesized gel. Besides, rheological analyses affirm its excellent viscoelastic nature. This network gel is biodegradable and its non-cytotoxic nature toward human dermal fibroblast cells is demonstrated. Moreover, the dual drug release pattern from the copolymer under both in vitro and in vivo conditions portrays that this hydrogel has superior ability to be used as a controlled release matrix for both hydrophobic and hydrophilic drugs (TCH and IB) with varying solubilities concurrently.

摘要

在医学科学中,有时需要同时使用两种溶解度不同的药物来治疗各种疾病。本文制备了一种 pH 响应的、共聚的、抗氧化的、生物相容的和化学交联的网络凝胶,以探索其作为同时控制释放疏水性(布洛芬(IB))和亲水性(盐酸四环素(TCH))药物的基质的能力。这种三维β-CD-Meth-cl-(PHPMA-PAAc)网络水凝胶通过两步合成:(I)β-环糊精的甲基丙烯酰化和(II)聚(羟丙基甲基丙烯酸酯)和聚丙烯酸的接枝,然后将聚乙二醇二丙烯酸酯交联到甲基丙烯酰化β-环糊精(β-CD-Meth)的主链上。使用多种物理化学特性对水凝胶的成功合成进行了确认。β-CD-Meth-cl-(PHPMA-PAAc)水凝胶具有极好的网络状表面形貌。潜在的 pH 响应高溶胀行为和优异的收缩特性表明合成凝胶具有可逆性。此外,流变学分析证实了其优异的粘弹性。这种网络凝胶是可生物降解的,并且对人皮肤成纤维细胞没有细胞毒性。此外,在体外和体内条件下从共聚物中释放两种药物的双重模式表明,该水凝胶具有作为同时控制释放具有不同溶解度的疏水性和亲水性药物(TCH 和 IB)的基质的优异能力。

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