Abstract
Purpose :
Curcumin (CUR) is recognized as a natural dietary compound that may have anti-VEGF properties. However, the pharmaceutical application of CUR is limited due to its poor water solubility and photodegradation. The goal of this research was to design amphiphilic polymeric micelles of the polyoxyethylated nonionic surfactant Pluronic F127 (PF127) as a carrier that can encapsulate CUR, thereby improving the bioavailability of CUR and prolong the residence time of the drug on the ocular surface.
Methods :
Micelle systems composed of PF127 were firstly evaluated as polymeric micelle carriers. Solutions of surface active PF127 at the critical micellar concentration (CMC) were prepared in deionized water (DI water). Subsequently, CUR was successfully loaded into PF127 using the thin-film hydration method. Loading of CUR into PF127 micelles was confirmed by several characterization techniques including DLS and HPLC. A detailed study of the effect of experimental conditions on both the particle size and drug encapsulation efficiency (%EE) of the CUR micelles was carried out, and in-vitro drug release and ex-vivo permeation were also studied.
Results :
The CMC of PF127 solution in DI water was found to be 0.21 ± 0.04 % (w/v). Characterization tests showed that CUR-loaded PF127 micelles (46-65 nm, PDI = 0.44-0.61) were larger than PF127 blank micelles (3-4 nm, PDI = 0.35-0.96), with negative zeta potential values. Moreover, the drug to polymer ratio was varied between 1:30 and 1:140, with a CUR encapsulation efficiency of 97% achieved at the 1:140 ratio. In addition, PF127 micelles enhanced the CUR solubility from 0.6 μg/mL up to 29 ug/ml for the highest drug-to-copolymer ratio. Furthermore, sustained release was obtained in vitro for CUR-loaded PF127 micelles (23%) over 10 days under sink conditions, and the ex-vivo drug diffusion study indicated a higher CUR retention in the cornea of the porcine eye of the CUR-loaded PF127 micelles (21 ± 8 ng/mg of tissue) compared to the control group (14 ± 2 ng/mg of tissue) after 24 h.
Conclusions :
These results suggest that PF127 micelles are a promising carrier for the delivery of CUR to the eye. Future work will study the ability of these micelles to transport CUR across ocular barriers by in vivo trials.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.