Dipartimento di Scienze Chimiche, Università di Cagliari, CNBS and CSGI, Cittadella Universitaria, s.s. 554 bivio Sestu, 09042 Monserrato (CA), Italy.
Biomacromolecules. 2011 Sep 12;12(9):3186-93. doi: 10.1021/bm200679w. Epub 2011 Aug 11.
This study was aimed to characterize the microstructure and the performance of gelatin microspheres (GMs) cross-linked by two different cross-linkers viz. d-glucose and glutaraldehyde. New formulations were obtained, suspending the GMs in a thermoreversible Pluronic F127 (PF127) liquid-crystalline gel. Lysozyme was used as a model biomacromolecular drug to evaluate release features. Both types of cross-linked GMs were prepared by thermal gelation method. The lysozyme-loaded microspheres were characterized by scanning electron microscopy (SEM) for size distribution, shape, and surface texture. SEM revealed that both types of lysozyme-loaded GMs were spherical in shape and that the surface of glutaraldehyde cross-linked GMs was smoother than that of the glucose cross-linked GMs. The degree of cross-linking of microspheres was investigated using ATR-FTIR technique. The prepared GMs were suspended in 20% w/v aqueous PF127 gel for which the usual sol-gel transition temperature of 22 °C did not change in the presence of GMs, as indicated by rheological measurements. SAXS study of the PF127 gel confirmed the occurrence of a discrete cubic liquid-crystalline phase of the Fm3m type whose lattice parameter slightly decreased as a result of GMs addition. The in vitro release of lysozyme from both types of cross-linked GMs was successfully controlled when they were suspended in PF127 gel, thus suggesting the potential use of this new combined formulation as a drug-depot system.
本研究旨在表征由两种不同交联剂(即葡萄糖和戊二醛)交联的明胶微球(GMs)的微观结构和性能。通过悬浮在热可逆 Pluronic F127(PF127)液晶凝胶中的 GMs 获得了新的配方。溶菌酶被用作模型生物大分子药物来评估释放特性。两种类型的交联 GMs 均通过热凝胶化方法制备。用扫描电子显微镜(SEM)对载溶菌酶的微球进行了大小分布、形状和表面纹理的特征描述。SEM 表明,两种类型的载溶菌酶的 GMs 均为球形,戊二醛交联 GMs 的表面比葡萄糖交联 GMs 的表面更光滑。使用 ATR-FTIR 技术研究了微球的交联程度。制备的 GMs 悬浮在 20% w/v 的 PF127 水凝胶中,流变测量表明,即使存在 GMs,凝胶的通常溶胶-凝胶转变温度 22°C 也没有改变。SAXS 研究证实了 Fm3m 型离散立方液晶相的存在,其晶格参数由于 GMs 的加入而略有减小。当两种类型的交联 GMs 悬浮在 PF127 凝胶中时,溶菌酶的体外释放得到了成功控制,因此表明这种新的组合配方具有作为药物储存系统的潜力。