Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig Maximilians University, Munich, Germany.
J Microencapsul. 2010;27(8):747-54. doi: 10.3109/02652048.2010.518773.
Gelatin nanoparticles (GNPs) have demonstrated to be beneficial as a biodegradable and biocompatible delivery system. So far, nanoparticles prepared by the two-step desolvation technique were subsequently cross-linked by glutaraldehyde to guarantee storage stability. Although in vivo and in vitro toxicological studies have not revealed any glutaraldehyde related undesired effects, an alternative to chemical cross-linking could ease future clinical use in humans. Therefore, the recombinant enzyme microbial transglutaminase was used to examine its cross-linking abilities in nanoparticle production. Various process parameters, such as incubation time, temperature, medium, pH and the particle purification were evaluated regarding their impact on particle size and its distribution. Cross-linking reactions were best at 25°C using an ion-free solvent at a neutral pH and have been terminated after 12 h. Preliminary storage stability testing indicated adequate consistency of particle size and particle distribution making transglutaminase a potential candidate for glutaraldehyde substitution in future GNP production.
明胶纳米粒子（GNPs）已被证明是一种可生物降解和生物相容的递药系统，具有良好的应用前景。迄今为止，两步去溶剂化技术制备的纳米粒子随后通过戊二醛交联，以保证储存稳定性。尽管体内和体外毒理学研究尚未发现戊二醛相关的不良影响，但替代化学交联方法可能会促进其未来在人类中的临床应用。因此，使用重组酶微生物谷氨酰胺转氨酶来研究其在纳米颗粒生产中的交联能力。评估了孵育时间、温度、介质、pH 值和颗粒纯化等各种工艺参数对粒径及其分布的影响。交联反应在 25°C 下、使用无离子溶剂和中性 pH 值条件下最佳，并且在 12 小时后终止。初步的储存稳定性测试表明，粒径和粒径分布具有足够的一致性，这使得转谷氨酰胺酶成为未来 GNP 生产中替代戊二醛的潜在候选者。
