Functionalization of polymeric nanomicelles and mixed nanomicelles for targeted retinal delivery in the management of retinoblastoma.

The current research discusses polymer conjugation, formulation development, and evaluation of sorafenib-loaded polymeric nanomicelles of conjugated soluplus (solu-tin) and polymeric mixed nanomicelles of conjugated soluplus (solu-tin) with conjugated poloxamer 188 (polo-tin) for site-specific posterior segment delivery to the retina in managing retinoblastoma. Firstly, the soluplus and poloxamer 188 were conjugated with biotin by Fischer esterification reaction and evaluated by FTIR and 1H NMR for confirmation of covalent bond formation involving the carboxyl group of biotin and hydroxyl group of polymers. Secondly, the sorafenib-loaded solu-tin nanomicelles and mixed nanomicelles of solu-tin with polo-tin were formulated by the thin film hydration method. Thereafter, these nanomicelles were evaluated and displayed suitable outcomes for particle size (78.53 nm and 73.17 nm), PDI (0.089 and 0.074), zeta potential (-3.65 mV and -4.17 mv), entrapment efficiency (99.23 % and 99.83 %), in vitro drug release (4 h and 8 h), solid-state analysis, osmolality (290 mOsm/kg and 293 mOsm/kg), pH (7.4 and 7.4), TEM (spherical) and residual solvent analysis (287.90 ppm and 363.49 ppm). The ex vivo transcleral permeation at 8 h was found to be 548.45 ng/cm2 and 281.61 ng/cm2, respectively. Both the drug-loaded nanomicelles displayed a dose-dependent anticancer effect on Y-79 cells at all time points i.e. 6, 12, 18, and 24 h, and were non-toxic to normal retinal pigmented epithelial cell line (ARPE-19) when incubated for 24 h. Furthermore, the formulations were non-irritant (HET-CAM) and stable for 6 months. Hence, the developed technology is safe and efficacious for targeting the retina in managing retinoblastoma.