EFFECT OF CROSSLINKER AMOUNT ON HYBRID HYDROGELS SWELLING AND DRUG RELEASE

M. Markovic, V. Panic, Julijana D. Tadić, R. Pjanovic
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Abstract

Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly water- soluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances.
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交联剂用量对杂化水凝胶溶胀及药物释放的影响
靶向给药是研究人员用来实现更安全、更有效治疗许多疾病的有力工具,包括各种类型的癌症。许多化疗药物的水溶性很差,因此它们的包封和靶向给药仍然是一个很大的挑战。基于聚甲基丙烯酸(PMAA)的水凝胶具有pH敏感性、无毒性和生物相容性等优点,被广泛用于药物靶向递送。然而,由于PMAA的高度亲水性,PMAA只能用于水溶性药物的包封和靶向递送。我们之前的研究旨在克服这一限制:用两亲性蛋白酪蛋白修饰PMAA,并包封难水溶性模型药物咖啡因(PMAC)。本文主要研究了交联剂这一最重要的水凝胶网络参数对PMAC溶胀性能和咖啡因释放的影响。以甲基丙烯酸为原料,以0.4mol%、0.8mol%、1.6mol%和3.2mol%的交联剂合成了杂化水凝胶基团PMAC。研究了混合水凝胶在模拟人胃和肠道两种环境下的溶胀行为和咖啡因的释放。结果表明,该方法可实现低水溶性模型药物的靶向递送,其释放时间可延长至24小时。此外,仅通过改变交联剂的用量就可以很容易地改变低水溶性药物的释放动力学。PMAC混合水凝胶在靶向递送难水溶性活性物质方面具有巨大的潜力。
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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