Trimethyl chitosan nanoparticles for ocular baicalein delivery: Preparation, optimization, in vitro evaluation, in vivo pharmacokinetic study and molecular dynamics simulation

To improve ocular bioavailability of baicalein (BAI), trimethyl chitosan coated lipid nanoparticles of baicalein (TMC-BAI-LNPs) were prepared, optimized and characterized. The properties of TMC-BAI-LNPs such as morphology, particle size, zeta potential and fourier transform infrared spectroscopy were investigated. Additionally, molecular dynamics simulation was applied as a new method to evaluate drug-biological membrane interactions. Transmission electron microscopy showed that the LNPs were approximately spherical in shape with a smooth surface. TMC-BAI-LNPs had a particle size of 162.8 nm, a positive surface charge with a zeta potential of 26.6 mV. The entrapment efficiency and drug loading values of BAI in the formulation were 90.65% and 2.04%, respectively. Moreover, in vitro drug release revealed that TMC-BAI-LNPs had a sustained release effect. In vivo studies indicated TMC-BAI-LNPs had no ocular irritation and the AUC of TMC-BAI-LNPs was 3.17-fold than that of the control (p < 0.01). Molecular dynamics simulation data showed that BAI had a poor membrane permeability, which limited the ocular bioavailability. The results indicated that TMC-BAI-LNPs might open up a new avenue for ocular administration. Furthermore, molecular dynamics simulation could predict permeability of drugs. (C) 2020 Elsevier B.V. All rights reserved.