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Transdermal co-delivery of glucosamine sulfate and diacerein for the induction of chondroprotection in experimental osteoarthritis

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Abstract

The aim of this work was to develop a transdermal delivery system consisting of a glucosamine sulfate–laden xanthan hydrogel containing a nanoemulsion-loaded diacerein. The system was intended to prevent cartilage degradation typical of osteoarthritis. The nanoemulsion, made of soybean oil as the oil phase; soybean lecithin, Tween 80, and poloxamer 407 as surfactants; and propylene glycol as cosurfactant, was formed within the hydrogel. The hydrodynamic diameter of the nanoemulsion globules was 81.95 ± 0.256 nm with 0.285 ± 0.036 of PDI value and the zeta potential value of the formulation was 39.33 ± 0.812 mV. CryoSEM and TEM studies revealed the uniform morphology of the vehicle. A rheological study exposed the nanoemulsion-loaded hydrogel as a thixotropic system. Satisfactory storage stability under ICH conditions was established by the zeta potential and rheological studies. Furthermore, skin biocompatibility of the hydrogel was ascertained on the basis of skin irritation study. Additionally, the diffusion of the drugs across rat skin followed a controlled non-Fickian anomalous steady mechanism. Following in vivo administration in experimental osteoarthritis, the transdermal hydrogel showed a reduction in tumor necrosis factor-alpha, C-reactive protein, high mobility group box protein, and monocyte chemoattractant protein-1. Finally, histopathological analysis of the animals showed satisfactory chondroprotection in the in vivo study. In conclusion, the developed transdermal systems showed a potential against the progression of experimental osteoarthritis.

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Acknowledgments

The authors are grateful to CRNN campus of University of Calcutta for carrying out the Cryo-SEM and TEM analyses.

Funding

This work has been funded by the DST INSPIRE fund (DST/ INSPIRE FELLOWSHIP/2012/575) and supported by the Department of Chemical Technology, C.U.

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Authors and Affiliations

  1. Department of Chemical Technology, University of Calcutta, 92, A.P.C. Road, Kolkata, 700 009, India

    Helen Chattopadhyay, Biswajit Auddy & Sriparna Datta

  2. Department of Pharmacology, Institute of Post Graduate Medical Education & Research, 244B, Acharya J.C Bose Road, Kolkata, 700020, India

    Tapas Sur

  3. Department of Dravyaguna, Institute of Post Graduate Ayurvedic Education and Research, 294/3/1, A.P.C. Road, Kolkata, 700 009, India

    Mradu Gupta

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  1. Helen Chattopadhyay
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  2. Biswajit Auddy
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Contributions

H.C. and S.D. conceived and designed the research. H.C. performed the formulation work. H.C., S.D., B.A., and T.S. designed and performed the animal study. M.G. provided animal ethics approval and facilities for in vivo studies. H.C., S.D., B.A., and T.S. analyzed and interpreted the results. H.C. wrote the manuscript, and S.D. edited the manuscript. All authors discussed the results and commented on the manuscript. All authors have given approval to the final version of the manuscript.

Corresponding author

Correspondence to Sriparna Datta.

Ethics declarations

The protocol of the experimental design was approved by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India, and by the Institutional Animal Ethics Committee (Registration no. 1180/ac/08/CPCSEA).

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The authors declare that they have no conflict of interest

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Chattopadhyay, H., Auddy, B., Sur, T. et al. Transdermal co-delivery of glucosamine sulfate and diacerein for the induction of chondroprotection in experimental osteoarthritis. Drug Deliv. and Transl. Res. 10, 1327–1340 (2020). https://doi.org/10.1007/s13346-019-00701-7

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