PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen—in vitro, ex vivo and in vivo characterization

•Dexibuprofen PEGylated nanospheres optimization was carried out by DoE.•Developed Dexibuprofen loaded nanospheres are suitable for ocular administration.•Nanospheres increase tropism to the cornea enhancing drug retention and permeation.•Developed formulations confirmed to be non-irritant by ocular tolerance assessment.•Formulations were effective both preventing and treating inflammation.

Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0 mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (­−14.1 and ­−15.9 mV), with a mean particle size below 200 nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12 h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in the sclera. These results were also confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration of drug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were less cytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET-CAM test) and in vivo (Draize test) tolerance assays demonstrated the non-irritant character of both nanosphere batches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammation induction. Both batches confirmed to be effective to treat and prevent ocular inflammation.

Graphical abstractBiodegradable PEGylated nanospheres loading Dexibuprofen demonstrated to be suitable for ocular inflammation treatment.Figure optionsDownload full-size imageDownload as PowerPoint slide