Fabrication of poloxamer based besifloxacin thermosensitive in situ gelling nanoemulsions for ophthalmic delivery

Abstract

The present study aimed to develop and investigate besifloxacin (BSF) in situ gel nanoemulsions (NEs) consisting of two hydrophilic polymers, that is, poloxamer 407 (P407) and poloxamer 188 (P188), for ocular delivery. BSF loaded in situ gel-NEs containing triacetin (oil), Cremophor®RH 40 (surfactant), Transcutol®P (co-surfactant), poloxamer 407 and poloxamer 188 (gelling agents) were prepared by spontaneous emulsification method. The optimum in situ gel nanoemulsion was selected based on gelation temperature. The selected formulation was evaluated for physicochemical characteristics, including droplet size, refractive index, pH, transparency, and viscosity. Further investigations such as in vitro drug release, ex vivo corneal permeation, HET-CAM, pre-corneal residence time antibacterial efficacy studies were conducted too. Developed BSF in situ gel nanoemulsion showed acceptable physicochemical properties with a nano-metric droplet size of 19 nm and PDI of 0.21. Moreover, In vitro release studies revealed that the in situ gel formulation could sustain drug release as only 40% of the BSF was released within 1 h. Permeability coefficient (Papp) of BSF through the excised bovine cornea was found 6.01 × 10−6 cm/s during 6 h. In addition, the HET-CAM evaluation confirmed the non-irritancy of the optimum BSF in situ gel NEs. The pre-corneal residence time evaluation indicated prolonged retention of in situ gel-NEs on the eye surface. Finally, antibacterial susceptibility investigations illustrated remarkable efficacy against Pseudomonas aeruginosa and Staphylococcus aureus. The current findings demonstrated that this proposed BSF-loaded in situ gel-NEs could be considered as a potential novel drug delivery formulation against ophthalmic bacterial infections.