Singh Somnath, Singh Jagdish
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Int J Pharm. 2004 Mar 1;271(1-2):189-96. doi: 10.1016/j.ijpharm.2003.11.010.
The purpose of this study was to investigate the suitability of phase sensitive smart polymer-based protein formulations in order to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time. Four different formulations, using D,L-poly(lactide) (D,L-PLA) and a solvent mixture of different ratios of benzyl benzoate (BB) and benzyl alcohol (BA), were prepared. Conformational stability and biological activity of lysozyme were studied by differential scanning calorimeter and enzyme activity assay, respectively. We found a significant (P < 0.05) increase in burst and rate of release of incorporated lysozyme from formulations containing greater proportion of BA. In order to increase the conformational stability and biological activity of lysozyme, we incorporated mannitol as stabilizer into formulations. Mannitol increased the conformational and biological activity of lysozyme in comparison to the control formulation prepared without mannitol. In conclusion, phase sensitive smart polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over extended period of time.
本研究的目的是研究基于相敏智能聚合物的蛋白质制剂的适用性,以便在较长时间内以可控速率递送模型蛋白溶菌酶,使其保持构象稳定且具有生物活性。制备了四种不同的制剂,使用了D,L-聚丙交酯(D,L-PLA)以及苯甲酸苄酯(BB)和苯甲醇(BA)不同比例的溶剂混合物。分别通过差示扫描量热法和酶活性测定研究了溶菌酶的构象稳定性和生物活性。我们发现,含有较大比例BA的制剂中,包封的溶菌酶的突释和释放速率有显著(P <0.05)增加。为了提高溶菌酶的构象稳定性和生物活性,我们将甘露醇作为稳定剂加入制剂中。与未添加甘露醇制备的对照制剂相比,甘露醇提高了溶菌酶的构象和生物活性。总之,基于相敏智能聚合物的递送系统能够在较长时间内以可控速率递送模型蛋白溶菌酶,使其保持构象稳定且具有生物活性。