Oil-free eye drops containing Cyclosporine A/SBECD/PVA supramolecular complex

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According to the global mapping of dry eye disease (DED), nearly 5 to 50 % of people suffer from DED, and this number is on the rise. The drug of choice Cyclosporine A (CsA) exhibits poor ocular bioavailability due to high molecular weight and lipophilicity. Moreover, formulations of CsA currently available are in the form of oil-based emulsions that are known to cause ocular irritation and pain. In this study, sulfobutylether-β-cyclodextrin (SBE-β-CD) based binary and ternary supramolecular complexes of CsA were developed as completely oil-free, and particle-free eye drops to treat DED. The physicochemical characterizations were supplemented with relevant in silico studies, to ascertain the findings. Further, the efficacy of the complexes was evaluated in the scopolamine-induced mouse model of DED. The complexation improved the CsA solubility by ~21-fold, with ~4-fold improvement in dissolution and transcorneal permeation. The non-irritancy and non-toxicity were confirmed by hen’s egg chorioallantoic membrane assay and cytotoxicity assay using human corneal epithelial cells, respectively. The in vivo treatment with the ternary CD complex demonstrated better management of the dry eye supported by the tear volume assessment, corneal fluorescein staining, and histopathological studies of the cornea, lacrimal gland, and harderian gland. The study demonstrates the potential of the supramolecular complex as an alternative to the oil-based formulation of eye drops for drugs that show low solubility and poor corneal permeation.

(a) Cell viability (%) of human corneal epithelial cells exposed to the test substances for 24 h (1) Cells only control, (2) 0.1 M NaOH, (3) 0.9 % NaCl, (4) distilled water,(5) Cyclomune, (6) SBE-β-CD, (7) PVA, (8) binary complex; and (9) ternary complex; and the (b) HET-CAM assay showing positive control 0.1 M NaOH, negative control 0.9 % NaCl, SBE-β-CD, PVA, distilled water, Cyclomune, binary complex; and ternary complex after 5 min of the treatment.

Chaudhari P, Birangal S, Mavlankar N, Pal A, Mallela LS, Roy S, Kodoth AK, Ghate V, Nampoothiri M, Lewis SA. Oil-free eye drops containing Cyclosporine A/cyclodextrin/PVA supramolecular complex as a treatment modality for dry eye disease. Carbohydr Polym. 2022 Dec 1;297:120007. doi: 10.1016/j.carbpol.2022.120007.

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