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智能膨胀生物聚合物微球的微流控方法:合成、原位包封和控制释放。

Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release.

机构信息

BIA-NANO, INRA, Rue de Géraudière, BP 71627, 44316 Nantes, France.

出版信息

Colloids Surf B Biointerfaces. 2011 Jan 1;82(1):81-6. doi: 10.1016/j.colsurfb.2010.08.020. Epub 2010 Aug 21.

DOI:10.1016/j.colsurfb.2010.08.020
PMID:20833004
Abstract

This paper reports a microfluidic synthesis of biopolymer microparticles aiming at smart swelling. Monodisperse aqueous emulsion droplets comprising biopolymer and its cross-linking agent were formed in mineral oil and solidified in the winding microfluidic channels by in situ chaotic mixing, which resulted in internal chemical gelation for hydrogels. The achievement of pectin microparticles from in situ mixing pectin with its cross-linking agent, calcium ions, successfully demonstrates the reliability of this microfluidic synthesis approach. In order to achieve hydrogels with smart swelling, the following parameters and their impacts on the swelling behaviour, stability and morphology of microparticles were investigated: (1) the type of biopolymers (alginate or mixture of alginate and carboxymethylcellulose, A-CMC); (2) rapid mixing; (3) concentration and type of cross-linking agent. Superabsorbent microparticles were obtained from A-CMC mixture by using ferric chloride as an additional external cross-linking agent. The in situ encapsulation of a model protein, bovine serum albumin (BSA), was also carried out. As a potential protein drug-delivery system, the BSA release behaviours of the biopolymer particles were studied in simulated gastric and intestinal fluids. Compared with alginate and A-CMC microparticles cross-linked with calcium ions, A-CMC microparticles cross-linked with both calcium and ferric ions demonstrate a significantly delayed release. The controllable release profile, the facile encapsulation as well as their biocompatibility, biodegradability, mucoadhesiveness render this microfluidic approach promising in achieving biopolymer microparticles as protein drug carrier for site-specific release.

摘要

本文报道了一种用于智能溶胀的生物聚合物微球的微流体制备方法。在矿物油中形成包含生物聚合物及其交联剂的单分散水乳液液滴,并通过原位混沌混合在蜿蜒的微流道中固化,导致水凝胶内部化学凝胶化。通过原位混合果胶与其交联剂钙离子成功制备出果胶微球,成功验证了这种微流体制备方法的可靠性。为了制备具有智能溶胀的水凝胶,研究了以下参数及其对微球溶胀行为、稳定性和形态的影响:(1)生物聚合物的类型(海藻酸钠或海藻酸钠和羧甲基纤维素的混合物,A-CMC);(2)快速混合;(3)交联剂的浓度和类型。通过使用三氯化铁作为额外的外部交联剂,从 A-CMC 混合物中获得了超吸水性微球。还进行了模型蛋白牛血清白蛋白(BSA)的原位包封。作为一种潜在的蛋白质药物传递系统,研究了生物聚合物颗粒在模拟胃液和肠液中的 BSA 释放行为。与钙离子交联的海藻酸钠和 A-CMC 微球相比,同时用钙离子和铁离子交联的 A-CMC 微球表现出明显延迟的释放。可控释放特性、易于包封以及它们的生物相容性、可生物降解性和黏膜黏附性使这种微流体制备方法有望实现作为蛋白质药物载体的生物聚合物微球的特定部位释放。

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