Understanding the influence of surface properties of nanoparticles and penetration enhancers for improving bioavailability in eye tissues in vivo.

Nanoparticulate drug delivery systems, mucoadhesive polymers and penetration enhancers have been used individually to overcome ocular barriers and increase bioavailability to eye tissues. However the combined influence of mucoadhesive polymer coating and penetration enhancers on NP permeability has not been investigated. Hence, in this study, three types of core-shell nanoparticles with same hydrophobic core but different hydrophilic mucoadhesive shells were developed. Initially the influence of a single penetration enhancer (PE) [benzalkonium chloride (BAC)] on ocular permeability of all the three core-shell nanoparticles was studied. Then ocular permeability of a single nanoparticle system [polycaprolactone-pluronicF68 (PCL-PF68)] in presence of different types of PEs namely BAC, capric acid (CA), EDTA, sodium glycocolate (SG) and sodium taurocholate (ST) was studied. The results indicated that BAC differentially enhanced ocular permeability of nanoparticles depending on their surface properties. All the PEs except EDTA enhanced ocular permeability of PCL-PF68 nanoparticles to anterior part of the eye. BAC and CA showed increased bioavailability of PCL-PF68 nanoparticles in conjunctiva, SG in cornea, iris and ciliary body, and ST in cornea. Overall, the combination of PEs and surface properties of nanoparticles can differentially influence ocular permeability and bioavailability and can be advantageously used to develop improved ocular drug delivery systems.