To investigate fit-to-purpose nanocarrier for non-invasive drug delivery to posterior segment of eye

Diseases of the posterior segment of the eye are difficult to treat due to lesser bioavailability of therapeutics at the posterior segment of the eye. Current clinical interventions involve administering drugs via invasive routes (Intravitreal, Retrobulbar, or Peribulbar) that bear the least patient compliance. Several nanocarriers strategies have shown a remarkable potential to deliver the loaded therapeutic to the posterior tissues of the eye. However, no one platform report was available to demarcate the most effective delivery system out of the recommended approaches. This investigation aimed at exploring a suitable and efficient non-invasive topically administrable nanocarriers system for the delivery of the drug to the posterior segment of the eye. Dexamethasone (DEX, a corticosteroid used for ocular inflammation) was selected as a model drug. The nanocarriers were formulated (size similar to 120 nm) and studied their potential at a common platform to deliver the drug to the posterior segment of the eye. The nanocarriers were analyzed for their in vitro drug release profile in simulated tear fluid (STF) depicting sustained release of DEX up to 24 h, ex-vivo corneal permeability, using excised goat cornea, cytotoxicity potential using human retinal pigment epithelium ARPE-19 cell lines, HET CAM assay to evaluate ocular irritancy, electrical resistance measurement across monolayers of Rabbit corneal epithelial cells SIRC and ARPE-19 cells and stability profiles, real-time qPCR IL-6 gene expression in ARPE-19 inflammation model. Ex-vivo corneal permeability demonstrated that the highest percentage of DEX was permeated by DEX-NLCs and lowest by DEX-SLNs. All the nanocarriers except DEX-CUBs depicted no cytotoxicity in ARPE-19 cells. All the nanocarriers depicted the change in electrical resistance measurement across monolayers of Rabbit corneal epithelial cells SIRC and ARPE-19 cells. They were also found to reduce the levels of IL-6 in gene expression assay depicting successful invitro delivery to ARPE-19 cells. However, only NLCs and NMFs were selected further as they demonstrated better potential to permeate after ex vivo and in vitro permeability studies. Further, in-vivo fluorescence imaging studies in Wistar rats were also performed with coumarin-6 loaded nanocarriers to deduce the effective and suitable candidate to deliver a drug to the posterior segment of the eye with the highest biosafety and permeability.

Automated summary

Diseases of the posterior segment of the eye are challenging to treat due to limited drug bioavailability. This study aimed to explore a non-invasive nanocarrier system for efficient drug delivery. Results showed that DEX-NLCs had the highest permeation percentage through the cornea, while DEX-CUBs exhibited no cytotoxicity in ARPE-19 cells. NLCs and NMFs were selected as the most promising carriers for further studies based on their superior permeation potential in both in vivo and in vitro studies.