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新型 pH 敏感的衣康酸-g-聚丙烯酰胺/乌桕胶半互穿网络的优化、体外释放及毒性评价。

Optimization, in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks.

机构信息

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

School of Pharmacy, The University of Faisalabad, Faisalabad, Faisalabad, Pakistan.

出版信息

Daru. 2021 Jun;29(1):171-184. doi: 10.1007/s40199-021-00395-8. Epub 2021 Apr 26.

Abstract

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.

摘要

背景

在最近的时代,将材料工程与医学相结合的 pH 敏感聚合物载体引起了研究人员的关注,因为它们可以使药物在吸收部位的浓度最大化,并减少副作用,例如口服西替利嗪盐酸盐(CTZ HCl)会刺激胃,并且具有较高的肠道吸收。因此,开发具有足够机械强度的 pH 敏感水凝胶将是解决此问题的良好候选物。

方法

在这里,我们通过自由基聚合技术开发了 pH 敏感的衣康酸-g-聚(丙烯酰胺)/蓖麻胶(IA-g-poly(AM)/蓖麻胶)半互穿网络(半 IPN),用于 CTZ HCl 的肠道传递。

结果

优化的配方(I5)在 pH 1.2 时具有可忽略不计的溶胀性,在 pH 7.4 时具有最大的溶胀性。优化配方的固态特性表明成功地开发了半 IPN 结构,并将药物掺入其中而没有任何明显的药物载体相互作用。体外释放研究表明 CTZ HCl 具有双相 pH 依赖性释放,其中在酸性 pH 下观察到初始突释,然后在碱性 pH 下持续释放。急性口服毒性和组织病理学研究证实了 IA-g-poly(AM)/蓖麻胶的非毒性。

结论

总之,开发出具有足够 pH 敏感性和机械强度的生物相容性半 IPN 水凝胶可以作为 CTZ HCl 肠道传递的潜在载体,以最大程度地提高其吸收并减少副作用。

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