(288) Development and in vitro Evaluation of Topical Multi-drug Nanomicelles for Treatment of Corneal Injury

Objective : Corneal healing is a critical process for restoring corneal integrity and maintaining vision after corneal injury. Based on the anatomical barriers possessed by cornea, our goal was to develop amphiphilic nanomicelles (NMs), which offer advantage of penetration and permit the drugs to reach the target site and improve their bioavailability. We have developed and evaluated PCL/PEG-based NMs loaded with dexamethasone (DEX), rapamycin (RAPA), and ciprofloxacin (CIP) for corneal treatment.

Methods: The five different arrangements and molecular weights of block copolymers were screened for NMs preparation, and PCL4k-PEG4k-PCL4k was selected for further studies based on size and loading. The DEX, RAPA, and CIP-loaded NMs were synthesized using nanoprecipitation method after applying the Design of Experiments. The physicochemical parameters of NMs such as surface morphology, size, entrapment, and loading efficiency of all three drugs-loaded NMs were characterized using DLS, NTA, and TEM and studied for in vitro release and kinetics. In vitro cell-based assays were performed on the human corneal epithelial cell line to evaluate biocompatibility of nanoformulations and cellular uptake was investigated by replacing drugs with fluorescent dye Coumarin.

Results: PCL4k-PEG4k-PCL4k block copolymer was characterized by NMR. Clear colloidal solutions of DEX, RAPA, and CIP-loaded NMs were obtained by nanoprecipitation method. DLS and NTA analysis of DEX, RAPA, and CIP- NMs showed spherical morphology with sizes of 82.4±1.2, 81.7±5.0, and 76.9±1.9 nm, respectively and PDI < 0.3 confirmed the monodispersity. The range of drug encapsulation in the NMs was about 80-90% for all three drugs. The NMs were found to be biocompatible and evaluated for cellular uptake apparently by endocytic pathway.

Conclusions: The multi-drug NMs were successfully optimized, and evaluated for biocompatibility, and cellular internalization on corneal cells.