Baicalin (BG) is a natural glycoside with several promising therapeutic and preventive applications. However, its pharmaceutical potential is compromised by its poor water solubility, complex oral absorption kinetics, and low bioavailability. In this work, BG was incorporated in a series of chitosan (Ch)/glycerophosphate (GP)-based thermosensitive hydrogel formulations to improve its water solubility and control its release profile. Molecular interactions between BG and GP were investigated using Fourier transform infrared spectroscopy (FT-IR), and the ability of GP to enhance the water solubility of BG was studied in different release media. Drug-loaded Ch/GP hydrogels were prepared and characterized for their gelation time, swelling ratio, and rheological properties in addition to surface and internal microstructure. Polyethylene glycol (PEG) 6000 and hydroxypropyl methyl cellulose (HPMC) were incorporated in the formulations at different ratios to study their effect on modulating the sol-gel behavior and the in vitro drug release. In vivo pharmacokinetic (PK) studies were carried out using a rabbit model to study the ability of drug-loaded Ch/GP thermosensitive hydrogels to control the absorption rate and improve the bioavailability of BG. Results showed that the solubility of BG was enhanced in the presence of GP, while the incorporation of PEG and/or HPMC had an impact on gelation time, rheological behavior, and rate of drug release in vitro. PK results obtained following buccal application of drug-loaded Ch/GP thermosensitive hydrogels to rabbits showed that the rate of BG absorption was controlled and the in vivo bioavailability was increased by 330% relative to BG aqueous oral suspension. The proposed Ch/GP thermosensitive hydrogel is an easily modifiable delivery platform that is not only capable of improving the solubility and bioavailability of BG following buccal administration but also can be suited for various local and injectable therapeutic applications.
Keywords: baicalin; bioavailability; chitosan; controlled release; thermosensitive hydrogels.