Preparation and Characteristics of a Thermosensitive in Situ Gel Loaded with Chitosan Nanoparticles for Optimal Ocular Delivery of Chloramphenicol

To enhance the antimicrobial activity of chloramphenicol (CAP) and extend ocular retention, chitosan nano-particles carrying chloramphenicol (CAP-CNPs) were prepared by ionotropic gelation technique and further incorporated into thermosensitive in situ gel (CAP-CNPs-Gel). The formulation of the thermosensitive gel was optimized using a central composite design-response surface methodology (CCD-RSM). The optimized CAP-CNPs-Gel was selected to investigate its drug release kinetics, antimicrobial activity, and ocular irritancy. The average particle size and zeta potential of the optimized CAP-CNPs were 137.5 +/- 3.6 nm and 29.9 +/- 0.3 mV, respectively. The gel matrix was found to be most effective with a combination of 20.5% (w/v) poloxamer 407 and 5.0% (w/v) poloxamer 188. The CAP-CNPs-Gel formulation demonstrated sustained drug release properties, with drug release lasting up to 18 h. Furthermore, CAP-CNPs-Gel exhibited superior antibacterial activity when compared to both CAP eye drops and CAP gel. Through in vivo studies, CAP-CNPs-Gel was shown to be well tolerated by the eyes and capable of prolonging precorneal retention time for up to 40 min. These promising results suggest that CAP-CNPs-Gel has the potential to serve as a reliable treatment for eye infections. Moreover, the thermosensitive nanoparticulate gelling system utilized in this study provides a valuable carrier for effective CAP delivery.