Interaction pattern and in vitro, in vivo release behavior of simvastatin-loaded chitosan nanoformulation

Abstract

Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis.

Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation.

Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV–vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation.

Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin.

Keywords:

• Chitosan
• simvastatin
• ligand titration
• NMR
• FT-IR

Disclosure statement

The authors declare that there is no conflict of interest in the manuscript.

Additional information

Funding

The authors acknowledge the financial support from WOS-B 2011 scheme of Department of Science and Technology, Government of India with ref. no. [SSD/SS/O26/2011].