Development of a novel ocular drug delivery system of levofloxacin nanoparticles embedded in 3D printed ophthalmic films

Abstract

This pilot research aimed to investigate a unique strategy for medication delivery to the eyes, using a customized medicine approach. This study used levofloxacin-loaded niosomes incorporated into 3D printed films to improve the effectiveness and bioavailability of therapy to those with eye diseases. Utilizing the accuracy of 3D printing techniques such as Stereolithography (SLA) for the production of ocular films. This research aimed to investigate the potential of levofloxacin loaded niosomes to be accompanied with various 3D SLA resins, with or without photoinitiators, to enhance the photopolymerization capacity of the resin when exposed to UV-light in a laboratory setting, prior to utilizing the SLA 3D printing device. The formulation of loaded niosomes was prepared using ether injection methods, as developed by Alyami et al. (2020). Subsequently, various characterization methods were employed to assess the release of niosomes, their entrapment efficiency, and compatibility. These methods included Differential Scanning Calorimetry (DSC) equipment, Fourier-transform infrared (FT-IR) spectroscopy, and Polarized Light Microscopic examination. This constituted the initial phase of the project. The second phase involved the utilization of SLA 3D printing to create a prototype using a computer-aided design (CAD) file. This was done to present the final printed product. Various types of SLA resins, including E-PVA, Commercial SLA resin, and Daylight Photocentric resin, were tested. For each resin, three batches were prepared: one as only resin, one with resin and 1% photoinitiators, and one with resin and 2% photoinitiators. The preparation was done using ice cube trays and the samples were exposed to UV-light. The samples were then evaluated and scored on a scale of 1 to 3 based on the degree of polymerization: score one indicated the absence of polymerization, score two indicated partial or incomplete polymerization, and score three indicated complete or full drying. Subsequently, the cubes experienced physiochemical assessment, including measurements of weight, diameter, friability, hardness, color characterization, and dissolution testing. The three sets of Daylight photocentric resin were effectively cured utilizing UV-light in the laboratory within a 10-minute timeframe, but the other batches of resin either experienced partial drying of the outer layer or failed to dry completely. The addition of levofloxacin niosomes formulation had two effects on the cube's formulations. Firstly, it caused the formation of bubbles, which required a proper mixing technique because of the viscosity of the resin. Secondly, it resulted in a change of the resin's color from yellow to gray. This issue could be resolved by using eye formulation preservatives. The Yellow photocentric cubes had a dissolution and disintegration test, and samples were collected at specific time intervals for measurement using HPLC. The cubes did not disintegrate or dissolve, leading to the formulation of new batches of photocentric resin. These new batches incorporated different disintegrants, namely HPMC 1% and Sodium alginate. The cubes remained undissolved; however, a little quantity of levofloxacin was identified in the phosphate buffer solution with a retention time of 3.5-4.5 minutes. The concentration of levofloxacin was below the limit of detection or quantification and thus could not be detected by HPLC. Further study is required to enhance the disintegration and dissolution properties of daylight photocentric resin cubes for their use in SLA printing, specifically for the development of a 3D ocular film capable of controlled medication release. The developed strategy has the potential to revolutionize the treatment of eye illnesses and drive advancements in the pharmaceutical sector by setting new benchmarks for the delivery of ocular drugs.