Topical Formulation of Self-Assembled Antiviral Prodrug Nanomicelles for Targeted Retinal Delivery

• DOI: 10.1021/acs.molpharmaceut.7b00128
• Publication Date: 2017-05-04T15:26:44Z
• Authors: Abhirup Mandal; Kishore Cholkar; Varun Khurana; Ankit Shah; Vibhuti Agrahari; Rohit Bisht; Dhananjay Pal; Ashim K. Mitra
• Keywords: Nanocarriers

Topical drug administration for back of the eye delivery is extremely challenging due to presence protection mechanisms and physiological barriers. Self-assembled polymeric nanomicelles have emerged as promising vehicles delivery. Apart from serving an inert nanocarrier therapeutic agents, are known bypass mononuclear phagocytic system (MPS) efflux transporters thereby improving bioavailability. In this investigation, a highly efficacious biotinylated lipid prodrug cyclic cidofovir (B–C12-cCDF) was formulated within carrier targeted retinal Polymeric were prepared polyoxyethylene hydrogenated castor oil 40 (HCO-40) octoxynol (OC-40). vitro release studies revealed that B–C12-cCDF-loaded released B–C12-cCDF at faster rate in stimulated tear fluid (STF) comparison PBST. MTT LDH assays demonstrated negligible cytotoxicity relative CDF HRPE (human pigment epithelial, D407), HCE-T corneal epithelial), CCL 20.2 conjunctival epithelial) cells. Confocal laser scanning microscopy flow cytometry analyses indicated efficiently internalized into D407 cells contrast B–C12-cCDF. Moreover, little also observed nuclei after 24 h incubation. carrying transporter did not produce any cytotoxic effects effectively. Permeability experiments across further confirmed significant transport loaded their subsequent uptake These findings indicate HCO-40/OC-40 based could become topical ocular antiviral agents.