No abstract

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargos to the retina. The new formulation, based on a gel core and composite shell, allowed up to two-fold increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affected the particle surface charge, colloidal stability, and cell internalization profile. We validated SLNs as a drug delivery system by performing the encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analog, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with a size of ±250 nm, anionic charge > −20 mV, and an encapsulation efficiency of ±60%, criteria that are suitable for retinal delivery. In vitro studies using the ARPE-19 and 661W retinal cell lines revealed the relatively low toxicity of SLNs, even when a high particle concentration was used. More importantly, SLN could be taken up by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all the characteristics suitable for the drug delivery of small hydrophilic active molecules into retinal cells.

Delivering small hydrophilic drug molecules to the retina is a challenging task in ophthalmology. A solid lipid nanoparticle (SLP) with a composite shell and hydrogel core as delivery system of a hydrophilic cargo to retinal cells has been developed in this work to meet the challenge. The composite shell formed by lipid and hydrophobic polyesters improves polydispersity while the hydrogel core enhances the encapsulation efficiency when compared to conventional SLP. In vitro studies tracking internalization and release of hydrophilic fluorescent dyes in retinal pigment epithelium and photoreceptor cell lines, showed a successful uptake and release of the hydrophilic cargo inside the cells. Validation of SLP encapsulation capability using a neuroprotective cGMP analogue resulted in a SLP size < 250 nm, negative surface charge > -20 mV, and encapsulation efficiency value of 60%. This formulation shows a potential to be applied as ocular drug delivery system and may open new perspectives for developing a treatment for retinal diseases.