Ter-polymeric Cytocompatible Hydrogels Based on Sodium Alginate with Pectin and Acrylic Acid for Controlled Loxoprofen Sodium Oral Delivery; In vitro and In vivo Evaluation

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Samiullah Khan, Abdur Rehman, Syed Faisal Badshah, Muhammad Saad
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引用次数: 0

Abstract

Purpose

Controlled and effective drug delivery remained a significant challenge in oral drug therapy. This study was conducted to design novel stable ter-polymeric hydrogels-based delivery system for controlled and effective Loxoprofen sodium release and in turn to reduce side effects after oral administration.

Methods

Current study reports the development of novel pH responsive ter-polymeric NaAlg/Pec/PAA hydrogels with varied feed composition synthesized via free radical polymerization technique. Swelling analysis and drug release study was conducted in various phosphate buffer solutions. Pharmacokinetic analysis in rabbit model was conducted to investigate the drug plasma concentrations with time. FTIR and SEM analysis was conducted to explore the structural and morphological investigations of optimized ter-polymeric hydrogels.

Results

Concluded that ter-polymeric NaAlg/Pec/PAA hydrogels exhibited maximum swelling and drug release in basic pH environment (7.5) owing to ionization of carboxyl (-COOH) groups which makes them excellent drug carriers to colon. It was also found that with increasing polymeric contents and crosslinker, gel fraction and porosity of hydrogels increased. Drug release kinetics showed that ter-polymeric hydrogels followed zero order release with non-fickian mechanism. MTT assay confirmed that developed blank and drug loaded hydrogels are biocompatible and safe for oral administration. In vivo analysis in animal model showed that ter-polymeric hydrogels exhibited controlled drug release (Cmax=2298.88 ng/ml) for 72 h in comparison to free Loxoprofen sodium solution (Cmax= 2337.50 ng/ml) for 40 min. FTIR analysis confirmed the new ter-polymeric hydrogel structure while SEM analysis showed the porous hydrogel structure.

Conclusion

It is concluded from results that Loxoprofen sodium adverse effect can be effectively controlled after oral administration via encapsulating in ter-polymeric hydrogels.

Graphical Abstract

Abstract Image

海藻酸钠-果胶-丙烯酸复合细胞相容性水凝胶用于控释洛洛芬钠体外和体内评价
目的控制和有效的给药仍然是口服药物治疗的一个重大挑战。本研究旨在设计一种新型的稳定的后聚合物水凝胶给药系统,以控制和有效地释放洛索洛芬钠,从而减少口服给药后的副作用。方法采用自由基聚合技术合成不同原料组成的新型pH响应型后聚NaAlg/Pec/PAA水凝胶。在不同的磷酸盐缓冲溶液中进行溶胀分析和药物释放研究。在家兔模型上进行药动学分析,观察药物血药浓度随时间的变化。利用FTIR和SEM对优化后的后聚合物水凝胶进行了结构和形态分析。结果NaAlg/Pec/PAA水凝胶由于羧基(-COOH)离子化,在碱性pH(7.5)环境下具有最大的溶胀和药物释放能力,是结肠药物的良好载体。随着聚合物含量和交联剂的增加,水凝胶的凝胶分数和孔隙率也随之增加。药物释放动力学表明,三聚水凝胶呈零级释放,具有非粘性机制。MTT试验证实所制备的空白和载药水凝胶具有生物相容性和口服安全性。动物模型体内分析表明,与游离洛索洛芬钠溶液(Cmax= 2337.50 ng/ml) 40 min相比,聚后水凝胶的释药时间为72 h (Cmax=2298.88 ng/ml)。FTIR分析证实了新型的后聚合物水凝胶结构,SEM分析显示了多孔水凝胶结构。结论洛索洛芬钠口服后经聚合物水凝胶包封可有效控制其不良反应。图形抽象
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来源期刊
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
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