Optimized molecular imprints in gamma-irradiated collagen shields of an antifungal drug: In vitro characterization, in-vivo bioavailability enhancement.

The purpose of this manuscript is to develop sustained release molecularly imprinted voriconazole (VOR) that were loaded into collagen shield (CS) for ocular treatment of fungal keratitis. Various molecularly imprinted polymer (MIP) formulae were prepared by a precipitation polymerization technique. Different monomers and crosslinkers were tested to obtain better binding capacity. Two promising formulae; (F1: VOR: Acrylamide: ethylene glycol dimethacrylate (EGDMA): benzoyl peroxide (BPO) in the molar ratio of 1:5:15:1.6 mM, respectively) and (F3: VOR: Acrylamide: methyl methacrylic acid (MMA): EGDMA: BPO in the molar ratio 1:2.5:2.5:15:1.6 mM, respectively) were selected according to their binding capacities (82.79% ± 0.86, and 94.90% ± 1.25 respectively), and their release profiles over 48 h in simulated tears fluid (STF) (41.64 ± 1.92, and 85.39 ± 1.64 respectively). Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) were carried out. The selected CS (F1 CS and F3 CS) showed sustained release profiles (57.38%± 0.72, and 98.51%±0.49 respectively) over 72 h in STF. Results of trans-corneal permeation and antifungal activity were enhanced for the optimized formula (F3 CS) compared to (F1 CS) and drug solution. Furthermore, in vivo pharmacokinetic studies were conducted showing significant increase in C, delayed T and promoted relative bioavailability. After ocular insertion of F3 CS in male albino rabbits, histopathological studies were attained to assure the safety of the formula. Finally, optimized VOR-MIP-CS could provide promising ocular drug delivery systems (DDS).