TY - JOUR
T1 - Oil-free eye drops containing Cyclosporine A/cyclodextrin/PVA supramolecular complex as a treatment modality for dry eye disease
AU - Chaudhari, Pinal
AU - Birangal, Sumit
AU - Mavlankar, Nimisha
AU - Pal, Asish
AU - Mallela, Lakshmi Sruthi
AU - Roy, Sanhita
AU - Kodoth, Arun K.
AU - Ghate, Vivek
AU - Nampoothiri, Madhavan
AU - Lewis, Shaila A.
N1 - Funding Information:
This research was funded by the Department of Biotechnology (DBT), Government of India, New Delhi ( BT/PR26970/NNT/28/1509/2017 ). The authors are grateful to the Manipal College of Pharmaceutical Sciences (MCOPS) and Manipal Academy of Higher Education (MAHE) for providing the necessary facilities for carrying out the research work. The authors are thankful to the Central instrumentation facility (CIF, Manipal) for providing a characterization facility. The authors would like to acknowledge Manipal - Schrödinger Centre for Molecular Simulations, MCOPS, Manipal for providing facilities to conduct the in silico studies.
Funding Information:
This research was funded by the Department of Biotechnology (DBT), Government of India, New Delhi (BT/PR26970/NNT/28/1509/2017). The authors are grateful to the Manipal College of Pharmaceutical Sciences (MCOPS) and Manipal Academy of Higher Education (MAHE) for providing the necessary facilities for carrying out the research work. The authors are thankful to the Central instrumentation facility (CIF, Manipal) for providing a characterization facility. The authors would like to acknowledge Manipal - Schrödinger Centre for Molecular Simulations, MCOPS, Manipal for providing facilities to conduct the in silico studies.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.carbpol.2022.120007
DO - 10.1016/j.carbpol.2022.120007
M3 - Article
AN - SCOPUS:85137032704
SN - 0144-8617
VL - 297
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
M1 - 120007
ER -
