PLGA Nanoparticles Containing Natural Flavanones for Ocular Inflammation

Abstract

Flavanones are natural compounds that display anti-inflammatory activity. The aimof this work was to prepare PLGA nanoparticles (NPs) containing natural flavanones I ((2S)-5,7-dihydroxy-6-methyl-8-(3-methyl-2-buten-1-il)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one) andII (2S)-5,7-dihydroxy-2-(40-methoxyphenyl)-6-methyl-8-(3-methyl-2-buten-1-yl)-2,3-dihydro-4H-1-Benzopyran-4-one) (NP I and NP II, respectively) so as to evaluate their potential for topical antiinflammatoryocular therapy. An in silico study was carried out using the Molinspiration® and PASSOnline web platforms before evaluating the in vitro release study and the ex vivo porcine corneaand sclera permeation. The HPLC analytical method was also established and validated. Finally, thein vitro anti-inflammatory efficacy of NPs was studied in the HCE-2 model. The flavanones I and IIcould be released following a kinetic hyperbolic model. Neither of the two NPs was able to permeatethrough the tissues. NP I and NP II were found to be respectful of any changes in the tissues’morphology, as evidenced by histological studies. In HCE-2 cells, NP I and NP II were not cytotoxicat concentrations up to 25 M. NP I showed higher anti-inflammatory activity than NP II, being ableto significantly reduce IL-8 production in LPS-treated HCE-2 cells. In summary, ocular treatmentwith NP I and NP II could be used as a promising therapy for the inhibition of ocular inflammation.