Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles

Abstract

This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic F127 and Pluronic F68 concentrations on the sol-gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application.

Keywords: desolvation method; diabetic retinopathy; ocular drug delivery; sustained release.

Figure 1

(A) Size distribution of Cur-BSA-NPs and (B) a transmission electron micrograph image of Cur-BSA-NPs. Abbreviation: Cur-BSA-NPs, curcumin-loaded albumin nanoparticles.

Figure 2

Response surface plot showing concentration effect of Pluronic^® F127 (X₁) and Pluronic^® F68 (X₂) on sol–gel transition temperature. Sol–gel transition temperatures of in situ gels before (A) and after (B) dilution both increased with the increased concentration of Pluronic F68 and decreased concentration of Pluronic F127.

Figure 3

Release curve (A) and erosion curve (B) of different formulations. Note: Most error bars are smaller than the symbols. Abbreviations: Cur-BSA-NPs, curcumin-loaded albumin nanoparticles; Cur-BSA-NPs-Gel, gel containing curcumin-loaded albumin nanoparticles; Cur-Gel, gel containing curcumin.

Figure 4

Concentration of curcumin in rabbit aqueous humor at various time points after instillation of different formulations. Note: n=5, mean ± standard deviation. Abbreviations: Cur-BSA-NPs-Gel, gel containing curcumin-loaded albumin nano-particles; Cur-sus, curcumin suspension.