Paroha Shweta, Dubey Ravindra Dhar, Verma Juhi, Jain Vikas, Akbar Saleem, Mishra Ashwini Kumar, Neha S L, Rani Laxmi, Mahto Aman Kumar, Sahoo Parvat Kumar, Dewangan Rikeshwer Prasad
Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University, New Delhi-110017, India.
Formulation Division, Invictus Oncology Private Limited, New Delhi-110092, India.
Curr Drug Deliv. 2025 Feb 12. doi: 10.2174/0115672018317615240926163652.
Gemcitabine (Gem) is a well-known antineoplastic drug used for several solid tumors. The clinical application of gem is hampered owing to non-selectivity, short half-life, and drug resistance, which necessitate the development of a suitable novel formulation that can selectively target cancer sites. In the present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared and coated with hyaluronic acid (HA-Gem-BSANPs). Particle size, zeta potential, TEM, and DSC analysis characterized the developed NPs. The mean particle size, PDI, and zeta potentials were observed to be 120.9 ± 5.87 vs 144.7 ± 5.67 and 28.66 ± 1.10 vs -45.72 ± 3.24, for Gem-BSANPs and HA-Gem-BSANPs, respectively. Interestingly, HA-coated Gem-BSANPs were found higher cytotoxic against A549 cell lines with better killing kinetics and mitochondrial membrane loss due to overexpression of CD44. The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve the therapeutic efficacy of gem by selectively targeting to the tumor site.
吉西他滨(Gem)是一种用于多种实体瘤的知名抗肿瘤药物。由于其非选择性、半衰期短和耐药性,吉西他滨的临床应用受到阻碍,这就需要开发一种能够选择性靶向癌症部位的合适新型制剂。在本研究中,制备了负载吉西他滨的牛血清白蛋白纳米颗粒(Gem-BSANPs)并用透明质酸进行包被(HA-Gem-BSANPs)。通过粒径、zeta电位、透射电子显微镜(TEM)和差示扫描量热法(DSC)分析对所制备的纳米颗粒进行了表征。Gem-BSANPs和HA-Gem-BSANPs的平均粒径、多分散指数(PDI)和zeta电位分别为120.9±5.87与144.7±5.67,以及28.66±1.10与-45.72±3.24。有趣的是,发现包被透明质酸的Gem-BSANPs对A549细胞系具有更高的细胞毒性,由于CD44的过表达而具有更好的杀伤动力学和线粒体膜损伤。本研究表明,HA-Gem-BSANPs可能是一种通过选择性靶向肿瘤部位来提高吉西他滨治疗效果的潜在策略。