pH-sensitive microparticles for oral drug delivery based on alginate/oligochitosan/Eudragit® L100-55 "sandwich" polyelectrolyte complex
pH-sensitive microparticles for oral drug delivery based on alginate/oligochitosan/Eudragit® L100-55 "sandwich" polyelectrolyte complex
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DOI：
10.1016/j.colsurfb.2013.05.016
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Milic, Jela
中科院分区：
文献类型：
--
作者：
Calija, Bojan;Cekic, Nebojsa;Milic, Jela
本研究的主要目的是研究低聚壳聚糖-乌达木聚糖(R) L100-55聚电解质复合物（OCH-EL PEC）对乌达木聚糖(R) L100-55处理的海藻酸-低聚壳聚糖微颗粒ph敏感性的影响。为了实现这一目标，在温和和环保的条件下，使用定制的装置，在共轴气流下制备了三种负载萘普生的微颗粒：海藻酸钙（Ca-ALG）、海藻酸-寡壳聚糖（ALG-OCH）和海藻酸-寡壳聚糖-乌龙木(R) L100-55 （ALG-OCH- el）微颗粒。干燥后，对微颗粒进行微观分析、物理化学和生物制药表征。通过热分析和红外光谱分析验证了OCH与EL在制备过程中的非共价相互作用以及OCH-EL PEC的形成。由于药物晶体（Ca-ALG颗粒）和OCH-EL PEC （ALG-OCH-EL颗粒）的存在，获得的颗粒具有可接受的球形度和表面粗糙度。结果表明，OCH-EL PEC对ALG-OCH颗粒的增强对其较高的包封效率（>74.4%）没有显著影响。药物释放研究结果证实了ALG-OCH PEC在pH 6.8和7.4下维持药物释放的能力。然而，在事先暴露于酸性培养基后，这种PEC对酸性环境和模拟肠液（pH值6.8）的敏感性增强。对ALG-OCH颗粒进行EL附加处理，形成“夹心”ALG-OCH-EL PEC，不仅可以提高药物在酸性介质中的稳定性，减少药物在酸性介质中的释放，而且可以在溶解介质pH提高到6.8后实现药物的持续释放。结果表明，ALG-OCH-EL微颗粒作为ph敏感的多颗粒药物载体用于口服非甾体抗炎药具有很大的潜力。(c) 2013 Elsevier B.V.版权所有
The primary objective of this study was to investigate the influence of the oligochitosan-Eudragit (R) L100-55 polyelectrolyte complex (OCH-EL PEC) on the pH-sensitivity of Eudragit (R) L100-55-treated alginate-oligochitosan microparticles. In order to achieve this, three types of naproxen-loaded microparticles were prepared under mild and environmentally friendly conditions using a custom made device with coaxial air flow: Ca-alginate (Ca-ALG), alginate-oligochitosan (ALG-OCH) and alginate-oligochitosan-Eudragit (R) L100-55 (ALG-OCH-EL) microparticles. After drying, the microparticles were subjected to microscopic analysis, and physicochemical and biopharmaceutical characterization. The non-covalent interaction between OCH and EL and the formation of OCH-EL PEC during the preparation procedure of the particles were verified by thermal and FT-IR analysis. The obtained particles exhibited acceptable sphericity and surface roughness due to the presence of the drug crystals (Ca-ALG particles) and OCH-EL PEC (ALG-OCH-EL particles). It was found that reinforcement of the ALG-OCH particles with OCH-EL PEC had no significant effect on the relatively high encapsulation efficiencies (>74.4%). The results of drug release studies confirmed the ability of ALG-OCH PEC to sustain drug release at pH 6.8 and 7.4. However, this PEC showed enhanced sensitivity to an acidic environment and to simulated intestinal fluid (pH 6.8) after prior exposure to an acidic medium. Additional treatment of ALG-OCH particles with EL and formation of "sandwich" ALG-OCH-EL PEC was essential not only to improve stability and decrease drug release in acidic medium, but also to achieve sustained release after the pH of dissolution medium was raised to 6.8. The obtained results suggested that ALG-OCH-EL microparticles have promising potential as pH-sensitive multiparticulate drug carriers for oral delivery of NSAIDs. (c) 2013 Elsevier B.V. All rights reserved.