1. Development and characterization of hyaluronic acid modified PLGA based nanoparticles for improved efficacy of cisplatin in solid tumor.
- Author
-
Alam N, Koul M, Mintoo MJ, Khare V, Gupta R, Rawat N, Sharma PR, Singh SK, Mondhe DM, and Gupta PN
- Subjects
- Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Cell Death drug effects, Cell Line, Tumor, Cisplatin pharmacology, Drug Liberation, Endocytosis drug effects, Humans, Nanoparticles ultrastructure, Neoplasms pathology, Particle Size, Spectroscopy, Fourier Transform Infrared, Static Electricity, Cisplatin therapeutic use, Hyaluronic Acid chemistry, Nanoparticles chemistry, Neoplasms drug therapy, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Cisplatin is a potent and widely used chemotherapeutic agent to treat a variety of tumors. However, its clinical use is associated with undesirable side effects and acquired resistance to cisplatin. In this study, cisplatin loaded hyaluronic acid (HA) functionalized poly (lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles (CP-HA-PLGA-PEG-NPs) were fabricated using double emulsion solvent evaporation method to target CD44 receptor expressed on cancerous cells. The developed nanoconstructs were characterized for various in vitro parameters, including size distribution, zeta potential, morphology, drug loading and in vitro release. The HA content on the HA-PLGA-PEG-NPs was quantified by a turbidimetric method. The in vitro anticancer study in human ovarian cancer (SKOV-3) cells showed significantly (p<0.05) higher cytotoxicity of CP-HA-PLGA-PEG NPs as compared to free cisplatin and non-targeted nanoparticles (CP-PLGA-PEG NPs). Further, laser scanning confocal microscopy revealed that there was enhanced cellular uptake of HA-PLGA-PEG NPs in CD44-over expressing ovarian cancer cell line (SKOV-3). The in vivo antitumor activity of CP-HA-PLGA-PEG-NPs was significantly (p<0.05) higher than free cisplatin and CP-PLGA-PEG-NPs in Ehrlich tumor (solid) bearing mice. The results demonstrated the potential of target specific nanoconstruct of cisplatin in the improved cancer chemotherapy., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF