Ige Pradum Pundlikrao, Dipsingh Solanki Nirmal
Department of Pharmaceutics and Quality Assurance, R C Patel Institute of Pharmaceutical Education and Research , Shirpur, Dhule, Maharashtra , India.
J Microencapsul. 2015;32(3):231-9. doi: 10.3109/02652048.2014.995731. Epub 2014 Dec 24.
This investigation explores the use of methoxy polyethylene glycol (mPEG) functionalised poly(D,L-lactide-co-glycolide) (PLGA) nanocrystals of flutamide (FLT) with enhanced solubility, bioavailability and blood circulation time for targeting prostate cancer. FLT had Log P 3.27, short half life 5-6 h, low water solubility, permeability and bioavailability with extensive first-pass metabolism. FLT-loaded nanocrystals were prepared using nanoprecipitation method with surface coating by mPEG and characterised through differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electronic microscopy, particle size, zeta potential, percent entrapment efficiency (% EE), in vitro dissolution, haemolysis, sterility, bioavailability and stability studies. The percent cumulative drug release and % EE of optimised formulation was found to be 95.21 ± 1.18 and 88.36 ± 1.20, respectively, for 48 h. In addition, FLT-loaded PEGylated PLGA nanocrystals exhibited significantly delayed blood clearance with drug level of about 766.71 ng/mL at 48 h. In conclusion, PEGylated PLGA FLT nanocrystals could be demonstrated as a novel approach to enhance solubility, bioavailability and blood circulation time.
本研究探索了用甲氧基聚乙二醇（mPEG）功能化的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米晶体包裹氟他胺（FLT），以提高其溶解度、生物利用度和血液循环时间，从而靶向治疗前列腺癌。氟他胺的脂水分配系数（Log P）为3.27，半衰期短（5 - 6小时），水溶性低，渗透性和生物利用度低，且存在广泛的首过代谢。采用纳米沉淀法制备了负载氟他胺的纳米晶体，并通过mPEG进行表面包覆，通过差示扫描量热法、傅里叶变换红外光谱法、X射线粉末衍射法、扫描电子显微镜、粒径、zeta电位、包封率（% EE）、体外溶出度、溶血、无菌性、生物利用度和稳定性研究对其进行了表征。优化制剂的累积药物释放百分比和包封率在48小时内分别为95.21 ± 1.18和88.36 ± 1.20。此外，负载氟他胺的聚乙二醇化PLGA纳米晶体的血液清除明显延迟，48小时时药物水平约为766.71 ng/mL。总之，聚乙二醇化PLGA氟他胺纳米晶体可被证明是一种提高溶解度、生物利用度和血液循环时间的新方法。
