Purchase this article with an account.
Sriram Gunda, Kishore Cholkar, Ravinder Earla, Ashim K. Mitra; Non-invasive Topical Drug Delivery To The Back Of The Eye: A Novel Aqueous Mixed Nanomicelle Formulation Of Sirolimus. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3257.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The objective of this study is to develop, optimize and characterize a stable aqueous mixed nanomicelle formulation of sirolimus. Also to determine the ocular tissue distribution of sirolimus upon topical drop administration of the formulation in rabbit model.
Vitamin E-TPGS and octoxynol-40 are mixed in varying ratios to obtain an optimized formulation. Sirolimus is a hydrophobic drug with a high logP value. The novel mixed nanomicellar formulation was prepared by solvent evaporation technique. The optimized formulation was characterized for its improvement in drug solubulization efficiency, osmolality and nanomicelle size. Thermal stability and regeneration time of mixed micelle formulation were also determined. In vivo drug ocular tissue distribution studies were conducted in male New Zealand rabbits by topical drops. Tissues were collected after 1h of topical drug administration. Sirolimus was extracted from tissue samples by liquid-liquid extraction method. Analysis was carried out using LC-MS/MS. Limit of quantization (LOQ) for retina-choroid tissue analysis was 3.5 ng/mL and other tissues was 10.48 ng/mL.
Sirolimus solubility had improved with the development of this novel mixed nanomicellar formulation to generate an overall concentration of 2mg/mL and 4mg/mL. The optimized formulation showed an effective micelle size of 25.3 nm with encapsulation percentage > 95% and osmolality of 295 mOsm/Kg respectively. Critical micelle concentration (CMC) was found to be at 0.012 wt%. The clarity of the formulation was determined by UV spectroscopy. Dissociation temperature of formulation was found to be above 90o C. Sirolimus concentrations were found in cornea, sclera and retina-choroid tissues. Drug concentrations in aqueous humor, vitreous humor and lens were found to be below limit of quantization. Mean drug concentration in the retina-choroid tissues were 350 ng/gm of tissue.
The novel mixed nanomicellar formulation had shown increase in the drug solubility with high entrapment. The nanomicelles exhibited smaller size with low poly dispersity index. High levels of sirolimus were observed in the retina-choroid after topical administration.
This PDF is available to Subscribers Only