Title

Formulation of simvastatin chitosan nanoparticles for controlled delivery in bone regeneration: Optimization using Box-Behnken design, stability and in vivo study

Author's Department

Chemistry Department

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https://reader.elsevier.com/reader/sd/pii/S037851732030020X?token=7E2C89765BEFF3EEB25757C9DF7FDD407AB5EC84B17FCCD73E7A95750E9D92FA7440C81AAA2BEB457DF25B53C622121B

All Authors

Wisam Khalaf Delan; Mai Zakaria; Basma Elsaadany; Aliaa N ElMeshad; Wael Mamdouh; Ahmed R Fares

Document Type

Research Article

Publication Title

International Journal of Pharmaceutics

Publication Date

1-15-2020

doi

https://doi.org/10.1016/j.ijpharm.2020.119038

Abstract

This study aims to formulate and optimize simvastatin loaded chitosan-tripolyphosphate nanoparticles (SIM CS-TPP NPs) using ionic gelation method to provide a local delivery system that controls and sustains the release of simvastatin in the desired dose to promote bone regeneration. Box-Behnken design was adopted for optimization of the formulation variables of the prepared nanoparticles namely, CS percentage, TPP percentage and homogenization time. The optimized formula was selected and characterized by transmission electronic microscopy, in-vitro release, swelling index and storage stability. The ability of the optimum formula to stimulate bone regeneration upon implantation in bone defect generated in rabbits was also evaluated. The optimum SIM CS-TPP NPs had particle size of 106 nm, zeta potential of 43.3 mv, polydispersity index of 0.295 and entrapment efficiency of 98.78% and also showed good storage stability over the first month in addition to controlled and steady release over 2 weeks that effectively delivered simvastatin in a therapeutic dose needed for bone regeneration. Cone beam computed tomography 3D images, bone density measurements and histopathological analysis confirmed the high potential of SIM CS-TPP NPs in promoting bone regeneration in the generated defects compared to both the non-medicated formula and untreated groups after 6 weeks of implantation.

First Page

1

Last Page

12

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