Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation

A chitosan-coated luteolin-loaded phytocubosomal system was prepared to improve the pharmacodynamic performance of luteolin in the treatment of glaucoma and ocular inflammation after topical ocular administration. Luteolin, a potent anti-oxidant herbal drug with poor aqueous solubility, was complexed with phospholipid. The prepared phytocubosomes were coated with chitosan, producing homogenously distributed nanosized particles (258 ± 9.05 nm) with a positive charge (+49 ± 6.09 mV), improved EE% (96 %), and increased concentration of encapsulated drug to 288 μg/ml. Polarized light microscopy revealed a cubic phase.

Chitosan-coated phytocubosomes showed a sustained drug release profile (38 % over 24 h) and improved anti-oxidant activity (IC50 of 32 μg/ml). Ex vivo transcorneal permeation was higher by 3.60 folds compared to luteolin suspension. Irritancy tests confirmed their safety in ocular tissues after single and multiple administrations. The pharmacodynamic studies on glaucomatous rabbit eyes demonstrated 6.46-, 3.88-, and 1.89-fold reductions in IOP of chitosan-coated phytocubosomes compared to luteolin suspension, cubosomes, and phytocubosomes, respectively. Pharmacodynamic anti-inflammatory studies revealed faster recovery capabilities of chitosan-coated phytocubosomes over other formulations. Thus, chitosan-coated phytocubosomes could be a promising ocular hybrid system for delivering herbal lipophilic drugs such as luteolin.

Materials

Poloxamer 407 was obtained from Fluka (Germany). Glyceryl-monooleate (GMO; Peceol®) was kindly provided by Gattefosse (France). Luteolin (LU) was purchased from Baoji Guokang Bio-Technology Co., Ltd., China. Chitosan (CS, low molecular weight; 85 % acetylation; viscosity, 20–200cps, molecular wt. 50,000–190,000 Da) was purchased from Sigma (MI, USA). Phospholipid S100 (PL) was obtained from Lipoid GmbH (Ludwigshafen, Germany).

Sarah Omran, Yosra S.R. Elnaggar, Ossama Y. Abdallah, Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation, International Journal of Biological Macromolecules, 2023, 127930, ISSN 0141-8130, https://doi.org/10.1016/j.ijbiomac.2023.127930.