Promising bioadhesive ofloxacin-loaded polymeric nanoparticles for the treatment of ocular inflammation: formulation and in vivo evaluation.

Our work tackles the combined advantages of both nanotechnology and the bioadhesive gel properties which were utilized to design an ocular drug delivery system that is capable to treat ocular inflammation. Nanoparticles encapsulating an antibiotic drug, ofloxacin, were fabricated using emulsion solvent evaporation technique adopting 23 full factorial design to evaluate the effect of formulation parameters: that is to say, the molecular weight of the polymer (polycaprolactone), amount of Kolliphor P188, and presence of the charge inducer (chitosan hydrochloride) on the measured responses: drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results show that the optimized LPCL-NP2 formulation (composed of low molecular weight polycaprolactone, 500 mg of Kolliphor P188, 0.25% chitosan hydrochloride, and 50 mg ofloxacin)  displayed a sphere shape with EE%, PS, PDI, and ZP values of 89.73 ± 0.04%, 195.4 ± 13.17 nm, 0.323 ± 0.01, and 55.4 ± 0.66 mV, respectively. DSC study confirmed the amorphous nature of the drug. The optimized nanoparticle formulation was then further incorporated into the following two ocular formulations: gel (LPCL-NP2-G4) and in situ forming gel (LPCL-NP2-ISG4). The penetration of optimized ocular formulations was assessed by confocal laser scanning microscopy. The antimicrobial study was conducted  for the following three ocular formulations: LPCL-NP2 presented as eye drops, LPCL-NP2-G4, and LPCL-NP2-ISG4 as well as the market product using rabbits which were infected in their eyes with Escherichia coli. Results revealed that rabbits treated with LPCL-NP2-ISG4 demonstrated a remarkable antibacterial efficacy and evident low bacterial growth which was additionally assured by the histopathological examination of eye biopsies compared with the other investigated groups. Thus, a novel ofloxacin-loaded nanoparticle formulation based on polycaprolactone is presented in the form of mucoadhesive non-irritating in situ forming ocular gel possessing a superior antibacterial activity. Graphical abstract.