Bhargave Hardik, Nijhawan Harsh, Yadav Khushwant S
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS Deemed to be University, Mumbai, 400056, India.
AAPS PharmSciTech. 2023 Apr 10;24(4):101. doi: 10.1208/s12249-023-02560-5.
The present study was undertaken to synthesize PEGylated monomethoxy poly (ethylene glycol)-poly (ε-Caprolactone) (mPEG-PCL) block copolymer and formulate Erlotinib HCl-loaded mPEG-PCL nanoparticles for enhancing the bioavailability of the drug. Using the ring-opening polymerization technique, PEGylated mPEG-PCL block copolymer was synthesized, and the structure of the copolymer was characterized using FTIR, H-NMR, and DSC techniques. The solvent evaporation approach was used to effectively encapsulate Erlotinib HCl within block copolymeric nanoparticles. Erlotinib HCl-loaded mPEG-PCL nanoparticles had a mean particle size of 146.5 ± 2.37 nm and a zeta potential of -27.8 ± 2.77 mV. The nanoparticles had a percent entrapment efficiency of 80.78 ± 0.09%. The in vitro drug release of Erlotinib HCl-loaded copolymeric nanoparticles showed a slow and sustained release behavior which could be maintained for up to 72 h. The Korsmeyer-Peppas fitting findings indicated that the drug release process followed a non-Fickian diffusion mechanism. The pharmacokinetic (PK) behavior of the developed nanoformulation was studied in albino Wistar rats, and the relative bioavailability of the optimized NP formulation given by intravenous route was found to be 187.33%. The PK data suggested that Erlotinib HCl-loaded mPEG-PCL copolymeric nanoparticles can dramatically alter the PK behavior of Erlotinib HCl and greatly improve the drug's bioavailability by as much as three times when compared to the oral formulation. As a result, it was established that the block copolymeric nanoparticles have promise for the effective encapsulation of Erlotinib HCL for an injectable formulation with increased bioavailability.
本研究旨在合成聚乙二醇化单甲氧基聚（乙二醇）-聚（ε-己内酯）（mPEG-PCL）嵌段共聚物，并制备载有盐酸厄洛替尼的mPEG-PCL纳米粒，以提高药物的生物利用度。采用开环聚合法合成了聚乙二醇化的mPEG-PCL嵌段共聚物，并通过傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）和差示扫描量热法（DSC）对共聚物的结构进行了表征。采用溶剂蒸发法将盐酸厄洛替尼有效地包封在嵌段共聚物纳米粒中。载有盐酸厄洛替尼的mPEG-PCL纳米粒的平均粒径为146.5±2.37 nm，ζ电位为-27.8±2.77 mV。纳米粒的包封率为80.78±0.09%。载有盐酸厄洛替尼的共聚物纳米粒的体外药物释放表现出缓慢且持续的释放行为，可持续长达72小时。Korsmeyer-Peppas拟合结果表明，药物释放过程遵循非Fickian扩散机制。在白化Wistar大鼠中研究了所开发纳米制剂的药代动力学（PK）行为，发现静脉给药的优化纳米粒制剂的相对生物利用度为187.33%。PK数据表明，载有盐酸厄洛替尼的mPEG-PCL共聚物纳米粒可显著改变盐酸厄洛替尼的PK行为，与口服制剂相比，可将药物的生物利用度提高多达三倍。因此，可以确定嵌段共聚物纳米粒有望有效地包封盐酸厄洛替尼，用于提高生物利用度的注射剂配方。
