Novel pH-sensitive gum ghatti-cl-poly(acrylic acid) composite hydrogel based on graphene oxide for metformin hydrochloride and sodium diclofenac combined drug-delivery systems†

Pragnesh N. Dave and Pradip M. Macwan
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Abstract

The objective of the present study was to synthesize pH-sensitive gum ghatti-cl-poly (acrylic acid)/GO hydrogels for the drug delivery and controlled combined release of metformin hydrochloride and sodium diclofenac. Gum ghatti (Gg) and acrylic acid (AA) were free radicals copolymerized using N,N‘-methylenebisacrylamide (MBA) and tetramethyl ethylenediamine as cross-linkers and ammonium persulfate (APS) as an initiator. The structure and surface morphology of the composite hydrogel were determined using FTIR and SEM analyses, respectively. The FTIR studies confirmed the successful acrylic acid and graphene oxide grafting and drug binding onto the backbone of the synthesized hydrogel. Drug-release kinetics and mechanisms were investigated using zero- and first-order kinetic models as well as the Korsmeyer–Peppas model, Higuchi model, and Hixson–Crowell model. Drug-release experiments revealed the important characteristics related with physiologically expected pH levels, including a high release rate at pH 9.2. At pH 9.2, metformin HCl drug release increased from 4.68% to 37.46%, whereas sodium diclofenac release increased from 3.25% to 54.75%. However, at pH 9.2, both metformin hydrochloride and sodium diclofenac showed non-Fickian transport mechanisms. In summary, combining drugs may reduce the efficacy of a single medication while influencing metabolic rescue mechanisms.

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用于盐酸二甲双胍和双氯芬酸钠联合给药系统的基于氧化石墨烯的新型 pH 值敏感性胶 Ghatti-cl 聚丙烯酸复合水凝胶†。
本研究的目的是合成 pH 值敏感的伽提胶-cl-聚(丙烯酸)/GO 水凝胶,用于盐酸二甲双胍和双氯芬酸钠的给药和联合控释。以 N,N'-亚甲基双丙烯酰胺(MBA)和四甲基乙二胺为交联剂,过硫酸铵(APS)为引发剂,自由基共聚了伽提胶(Gg)和丙烯酸(AA)。傅立叶变换红外光谱和扫描电镜分析分别测定了复合水凝胶的结构和表面形态。傅立叶变换红外光谱研究证实了丙烯酸和氧化石墨烯成功接枝并与药物结合到合成水凝胶的骨架上。利用零阶和一阶动力学模型以及 Korsmeyer-Peppas 模型、Higuchi 模型和 Hixson-Crowell 模型研究了药物释放动力学和机制。药物释放实验显示了与生理预期 pH 值相关的重要特征,包括 pH 值为 9.2 时的高释放率。在 pH 值为 9.2 时,盐酸二甲双胍的药物释放率从 4.68% 增加到 37.46%,而双氯芬酸钠的释放率则从 3.25% 增加到 54.75%。不过,在 pH 值为 9.2 时,盐酸二甲双胍和双氯芬酸钠都显示出非菲克转运机制。总之,联合用药可能会降低单一药物的疗效,同时影响代谢救援机制。
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