UGC Centre for Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
UGC Centre for Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Int J Pharm. 2012 Apr 15;426(1-2):132-143. doi: 10.1016/j.ijpharm.2012.01.005. Epub 2012 Jan 13.
An injectable, phase sensitive, in situ forming, implantable delivery system was developed for enfuvirtide, a therapeutic peptide used in the treatment of HIV infection. The development studies were carried out using poly (D,L-lactide-co-glycolide), a smart, biodegradable polymer. Different formulations were designed, prepared and evaluated by employing response surface, optimal design of experiment technique. The optimized formulation was identified and validated for its performance by using numerical optimization technique. The in vitro evaluation parameters included rheology, compatibility studies, drug release as well as conformational and physicochemical stability studies. In vivo pharmacokinetic parameters and biocompatibility studies were determined in rat models and were statistically analyzed. It was found that the optimized formulation extended the enfuvirtide release and maintained the drug plasma concentration within therapeutically effective range up to 48 h. The optimized formulation maintained physicochemical and conformational stability for at least 6 months and was biocompatible with the animal tissue.
开发了一种可注射的、相敏的、原位形成的、可植入的药物传递系统，用于治疗 HIV 感染的治疗性肽恩夫韦肽。使用智能可生物降解聚合物聚（D，L-丙交酯-共-乙交酯）进行了开发研究。通过使用响应面、实验设计技术的最佳设计，设计、制备和评估了不同的配方。通过数值优化技术对优化配方的性能进行了识别和验证。体外评估参数包括流变学、相容性研究、药物释放以及构象和物理化学稳定性研究。在大鼠模型中进行了体内药代动力学参数和生物相容性研究，并进行了统计学分析。结果发现，优化的配方延长了恩夫韦肽的释放，并将药物血浆浓度维持在治疗有效范围内长达 48 小时。优化的配方至少在 6 个月内保持物理化学和构象稳定性，并且与动物组织具有生物相容性。
