Novel scheme for rapid synthesis of hollow mesoporous silica nanoparticles (HMSNs) and their application as an efficient delivery carrier for oral bioavailability improvement of poorly water-soluble BCS type II drugs.

Abstract

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for drug delivery. However, a facile method to synthesize HMSNs has hardly been reported so far. The primary objective of our current study was to develop HMSNs using a simple, quick, and inexpensive method and evaluate their ability to enhance solubility, dissolution rate, and bioavailability of poorly water-soluble model BSC type II drug Carvedilol. Traditional mesoporous silica nanoparticles (MSNs) are synthesized using classical Stober method and HMSNs with an entire hollow core was induced by immersing cetyltrimethylammonium bromide (CTAB) in hot water. Initial MSNs were added in boiling distilled water to synthesize hollow structure, to enhance pore size, and also to remove CTAB template. HMSNs prepared in our current study has exhibited high surface area (886.84 m2/g), pore volume (0.79 cm3/g), and uniform pore size (3.18 nm), which also enabled the greater encapsulation of the model BSC II drug Carvedilol (CAR) inside the HMSNs. This technique also helped in achieving a high drug loading of (40.22 ± 0.73)%. Add to all this, in vitro studies conducted in the present work showed that compared with pure CAR and CAR loaded MSNs (CAR-MSNs) synthesized by Stober method, the drug-loaded HMSNs (CAR-HMSNs) exhibit sustained drug release performance. The high drug loading and sustained release can be attributed to the hollow porous structure of the HMSNs. Finally, a pharmacokinetic analysis in rats indicated a significant increase in bioavailability of carvedilol HMSNs in vivo compared to the pure carvedilol and carvedilol loaded MSNs. This study, therefore, offered a new, simple, and quick method to develop HMSNs with the ability to support higher loading and controlled release behavior in vitro and enhanced absorption of poorly-aqueous soluble drugs in-vivo.