A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization, Ex-Vivo Imaging, and In Vivo Evaluation.

Lijie Wang,Haowei Sun,Kai Chen,Weisan Pan,Hao Pan,Donghao Gu,Guoxin Tan

doi:10.3390/ijms22189934

Abstract

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.

Highlights

IntroductionEye diseases seriously affect human health and quality of life [2]
The results showed that CDC-HP carbon dots have antibacterial ability, which is of great significance for the development and the storage of carbon dots for ocular drug delivery applications
A novel composite ocular drug delivery system in which drug Carbon dots (C-dots) particles are embedded in a thermosensitive in situ gel was developed and characterized

Summary

Introduction

Eye diseases seriously affect human health and quality of life [2]. Ophthalmic inflammation is one of the most common diseases in our daily lives, but it is one of the most overlooked. The first line of treatment for ophthalmic inflammation is broad-spectrum antibiotics [3]. Prolonged use of antibiotics will lead to bacterial resistance, and antibiotics abuse can trigger drugderived eye diseases and further cause eye damage. DS eye drop solutions are the main dosage form for relieving ocular inflammation. Its bioavailability is only 5% due to the multiple protective barriers in the eye. There is an urgent need for a formulation design that can reduce the frequency of dosing and improve the bioavailability of DS through continuous ocular delivery and improved ocular penetration

Results

Discussion

Conclusion