Design, optimization and in vitro-in vivo evaluation of smart nanocaged carrier delivery of multifunctional PEG-chitosan stabilized silybin nanocrystals

Abstract

This study explored the feasibility of using smart nanocaged carrier technology for the delivering of multifunctional mPEG-chitosan stabilized silybin nanocrystals and to enhancing the long-term stability, dissolution velocity and bioavailability of the water insoluble drugs. The methoxypoly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL), as nanocaged carrier, was modified with propargyl and azide group and confirmed by FTIR. The methoxypolythylene glycol-grafted chitosan (PEG-CS), as multifunctional stabilizer, were applied for the silybin nanocrystals formulation. Two silybin nanocrystals formulations (PEG-CS nanocrystals and nanocaged nanocrystals) were prepared using anti-solvent precipitation method and optimized by central composite design-response surface model. The transmission electron microscopy, scanning electron microscopy and atomic force microscope revealed small and uniformed morphology. The crystalline state of the nanocrystals was confirmed by X-ray powder diffraction and differential scanning calorimetry. The drug structure was confirmed by Fourier transform infrared spectroscopy. During the long term stability study, the nanocaged nanocrystals were presented remarkable stability. Compared with the silybin solution, the nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC, respectively. Thus, the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.