一种用于持续联合治疗的可注射药物递送平台。

An injectable drug delivery platform for sustained combination therapy.

作者信息

Baumann M Douglas, Kang Catherine E, Stanwick Jason C, Wang Yuanfei, Kim Howard, Lapitsky Yakov, Shoichet Molly S

机构信息

Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, Canada.

出版信息

J Control Release. 2009 Sep 15;138(3):205-13. doi: 10.1016/j.jconrel.2009.05.009. Epub 2009 May 13.

Abstract

We report the development of a series of physical hydrogel blends composed of hyaluronan (HA) and methyl cellulose (MC) designed for independent delivery of one or more drugs, from 1 to 28 days, for ultimate application in spinal cord injury repair strategies. To achieve a diversity of release profiles we exploit the combination of fast diffusion-controlled release of dissolved solutes from the HAMC itself and slow drug release from poly(lactide-co-glycolide) particles dispersed within the gel. Delivery from the composite hydrogels was demonstrated using the neuroprotective molecules NBQX and FGF-2, which were released for 1 and 4 days, respectively; the neuroregenerative molecules dbcAMP and EGF, and proteins alpha-chymotrypsin and IgG, which were released for 28 days. alpha-chymotrypsin and IgG were selected as model proteins for the clinically relevant neurotrophin-3 and anti-NogoA. Particle loaded hydrogels were significantly more stable than HAMC alone and drug release was longer and more linear than from particles alone. The composite hydrogels are minimally swelling and injectable through a 30 gauge/200 microm inner diameter needle at particle loads up to 15 wt.% and particle diameters up to 15 microm.

摘要

我们报告了一系列由透明质酸(HA)和甲基纤维素(MC)组成的物理水凝胶混合物的研发情况,这些混合物旨在独立释放一种或多种药物,释放时间为1至28天,最终应用于脊髓损伤修复策略。为了实现多种释放曲线,我们利用了溶解溶质从HAMC本身的快速扩散控制释放与分散在凝胶中的聚(丙交酯-共-乙交酯)颗粒的缓慢药物释放相结合的方式。使用神经保护分子NBQX和FGF-2证明了复合水凝胶的释放情况,它们分别释放1天和4天;神经再生分子dbcAMP和EGF,以及蛋白质α-糜蛋白酶和IgG,它们释放28天。选择α-糜蛋白酶和IgG作为临床相关神经营养因子-3和抗NogoA的模型蛋白。负载颗粒的水凝胶比单独的HAMC显著更稳定,药物释放比单独的颗粒更长且更呈线性。复合水凝胶在颗粒负载高达15 wt.%且颗粒直径高达15微米时,溶胀最小,可通过30号/200微米内径的针头注射。

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