A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin.

Na Sai,Xin Leng,Yingchao Yu,Yi Liu,Jian Ni,Xingbin Yin,Changhai Qu,Pingqing Huang,Wenping Wang,Xiaoxv Dong,Huimin Wu,Longtai You,Yuanyuan Du,Chunjing Yang

doi:10.3390/molecules25010081

Abstract

Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.

Highlights

The topical application of eye drops is still the most common and well-accepted approach for the treatment of ocular diseases
The results showed that the Critical Micelle Concentration (CMC) values of micelles with a Solutol HS 15 and PEG-DSPE ratio of 3:2 (w/w) were the lowest, indicating that the micelles were the most stable at a ratio of 3:2 [12]
In order to improve the solubility, stability, and corneal permeability of curcumin, a novel ophthalmic gel-forming solution based on PEG-DSPE/Solutol HS 15 mixed micelle in situ gel was constructed in this study

Summary

Introduction

The topical application of eye drops is still the most common and well-accepted approach for the treatment of ocular diseases. In order to overcome the disadvantages associated with conventional eye drops, many ocular drug delivery systems have been recently formulated and evaluated. These systems include polymeric micelles, liposomes, dendrimers, oil-water lipid emulsions, and nanoparticles. These delivery systems improve the ocular bioavailability of drugs and reduce severe adverse effects [4]. In situ gel-forming systems (comprising thermosensitive gels, pH-sensitive gels, and ion-sensitive gels) are viscous liquids used to enhance precorneal retention time. They are capable of transitioning to a gel phase upon exposure to physiological conditions. To exploit the benefits of these two dosage forms, we proposed polymeric micelles incorporated in situ ocular gel for ophthalmic drug delivery

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