Lauric acid-grafted biopolymeric nanoparticles for efficient Melphalan delivery across the corneal layers for retinoblastoma: ex vivo and in vivo permeation study

Intravitreal injection of chemotherapy drugs for intraocular retinoblastoma, for the prevalent pediatric malignancy treatment with the side effects of severe infection. This study tried to synthesize the novel approach to deliver Melphalan to the vitreous cavity through the cornea to increase drug efficacy with non-invasive effects. For this purpose, lauric acid-grafted chitosanalginate and chitosan-alginate loaded by Melphalan nanoparticles were fabricated. Fouriertransform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were the basic characterizations of chitosan modification. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) are the other assessments of synthesized nanoparticles. Drug encapsulation and in vitro release were studied using UV-spectroscopy, also ex vivo and in vivo corneal permeation was studied using Franz diffusion cell, fluorescence microscopy, and in vivo animal imaging. FTIR and XRD confirm the successful grafting of lauric acid and spherical shape with the average size of 50 nm and 80 nm observed for modified and chitosan-alginate nanoparticles respectively. In the release study, encapsulation efficiency of 98% with sustained drug release of 80% for 100 h with the Fickian drug diffusion mechanism was reported. Ex vivo corneal permeation exhibited an improved drug penetration rate in the sample of lauric acidgrafted-chitosan-alginate nanoparticles with the results of 5.8 times higher than chitosan-alginate nano-carriers and 15.5-fold compared to drug solution. Also, in vivo study shows that the designed nanoparticles containing Melphalan reached the vitreous cavity with high efficacy. Current investigations illustrate the novel Melphalan delivery with sustained behavior through the cornea with the high potential of corneal layer penetration for retinoblastoma management.