Formulation and development of colon-targeted mucopenetrating metronidazole nanoparticles

Purpose: To formulation and develop colon-targeted mucopenetrating metronidazole nanoparticles.
Methods: Metronidazole-loaded chitosan nanoparticles with a pH-sensitive polymer, hydroxyl propyl methyl cellulose phthalate (HPMCP), were prepared by ionic gelation technique and then coated with Eudragit S100 by solvent evaporation method. The nanoparticles were optimized using one variable at a time (OVAT) approach. Further, the nanoparticles were evaluated by scanning electron microscopy (SEM) and zeta sizer, as well as for in-vitro release. Muco-adhesion was evaluated by modified bioadhesion detachment force measurement balance and muco-penetration of fluorescein isothiocyanate (FITC) labeled optimized nanoparticles was determined by microscopic technique
Results: Morphological assessment results revealed smooth, spherical particles with homogeneous distribution and polydispersity index (PDI) of 0.213. The optimized formulation showed particle size of 202 ± 27 nm, zeta potential of 26.9 ± 2.4 mV as well as and entrapment efficiency of 79 ± 5.4 %. There was significant difference in drug release between coated (8.46 ± 2.49 %) and uncoated (28.96 ± 4.04 %) nanoparticles at the 5th h in simulated gastric conditions. Muco-adhesion data revealed that uncoated nanoparticles (14.98 x 103 dyne/cm2) showed higher muco-adhesion detachment force compared to coated (12.34 x 103 dyne/cm2) nanoparticles. Muco-penetration results confirm the retention (for up to 12 h) of the developed formulation at the target site for enhanced therapeutic exposure of the entrapped drug.
Conclusion: Eudragit S100 coating of chitosan-HPMCP nanoparticles promotes efficient drug targeting and thus provides a strategy for treating mucosal infections. .

Keywords
Metronidazole; pH-sensitive nanoparticles; Hydroxylpropyl methylcellulose phthalate; Ionic gelation; Mucoadhesion; Mucopenetration; Intestinal infection