Investigation of in vitro permeability and in vivo pharmacokinetic behavior of bare and functionalized MCM-41 and MCM-48 mesoporous silica nanoparticles: a burst and controlled drug release system for raloxifene

Abstract

In the present work, MCM-41 and MCM-48 type of nanoparticles were successfully engineered. Effect of nanosize and amine functionalization on drug release, in vitro intestinal absorption and in vivo pharmacokinetic behavior was investigated in a comprehensive manner. The tailor-made bare and surface decorated MCM-41 and MCM-48 were synthesized and evaluated for their mesoporous skeleton, pore size, particle size, surface area, zeta potential, etc. by nitrogen sorption, DLS, TEM, etc. Incorporation of raloxifene (RLF) was affirmed using optimized immersion-solvent evaporation technique and its success confirmed by DSC, IR, and XRD analysis. TGA analysis revealed higher %grafting of amine groups on the exterior and larger RLF encapsulation into mesoporous derivate. The detailed in vitro release study revealed SGF to be the most compatible media for RLF showing an initial burst release from pristine nanoparticles and a delayed release from surface coated nanoparticles. Furthermore, release kinetics model data demonstrated Weibull and Higuchi as the best fit models for bare and amine-functionalized nanoparticles respectively. Moreover, an in vitro permeability study on Caco-2 cell line revealed higher absorption by engineered nanoparticle as compared to pure RLF and its marketed formulation. The supremacy in the in vivo pharmacokinetic parameters of RLF-41 and RLF-48 was demonstrated with 3.33 and 3.50 times enhancement in the bioavailability of RLF with respect to RLF suspension. To sum up, the results obtained were superior and promising for synthesized nanoparticles and more precisely for MCM-48 amongst them.

Keywords:

• Raloxifene hydrochloride
• MCM-41
• MCM-41-NH2
• MCM-48
• MCM-48-NH2
• Caco-2 transport
• pharmacokinetic study

Acknowledgements

The authors are thankful to Zydus cadilla healthcare, Ahmedabad for providing swiss albino female mice to carry out the pharmacokinetic study. We also heartily thank them for providing pharmaceutical grade RLF as a gift sample.

Disclosure statement

No potential conflict of interest was reported by the authors.