The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200 nm and entrapment efficiency of ≈14%. In vitro drug release studies revealed cumulative release of 14.07 ± 0.57% and 22.02 ± 0.81% of rosuvastatin over the period of 120 h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72 h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for ‘statins’.
|Number of pages
|International Journal of Biological Macromolecules
|Published - 01-02-2018
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology