新型 pH 值敏感的衣康酸-聚丙烯酰胺/紫胶半互穿网络的优化、体外释放和毒性评估。

Fauzia Rehman, Ikram Ullah Khan, Syed Haroon Khalid, Sajid Asghar, Muhammad Irfan, Ikrima Khalid, Akhtar Rasul, Huma Mahmood, Abid Mehmood Yousaf, Yasser Shahzad, Muhammad Mudassar, Noor Ul Amin Mohsin
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引用次数: 0

摘要

背景:近年来,结合材料工程学和医学的 pH 值敏感聚合物载体越来越受到研究人员的关注,因为它们能最大限度地提高药物在吸收部位的浓度并减少副作用,例如口服盐酸西替利嗪(CTZ HCl)会扰乱胃部,而且肠道吸收率很高。因此,开发具有足够机械强度的 pH 值敏感型水凝胶将是解决这一问题的好方法。方法:在此,我们采用自由基聚合技术开发了 pH 值敏感型衣康酸-聚丙烯酰胺/槲皮胶(IA-聚(AM)/槲皮胶)半互穿网络(semi-IPN),用于盐酸西替利嗪(CTZ HCL)的肠道给药:结果:含 6% w/w IA 的优化配方(I5)在 pH 值为 1.2 时的溶胀可忽略不计,而在 pH 值为 7.4 时溶胀最大。优化制剂的固态表征表明,该制剂成功地形成了半 IPN 结构,并成功地掺入了药物,没有出现任何明显的药物-载体相互作用。体外释放研究表明,盐酸 CTZ 的释放与 pH 值呈双相依赖关系,在酸性 pH 值下会出现最初的猝灭释放,随后在碱性 pH 值下会出现持续释放。急性口服毒性和组织病理学研究证实了 IA-g-poly(AM)/sterculia 胶的无毒性:结论:所开发的生物相容性半 IPN 水凝胶具有足够的 pH 值敏感性和机械强度,可作为一种潜在的载体用于 CTZ HCL 的肠道给药,从而最大限度地提高其吸收率并减少副作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimization, in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks.

Background: In recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher's attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.

Methods: Here, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.

Results: Optimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.

Conclusion: Conclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.

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