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Development and evaluation of novel krill oil-based clomiphene microemulsion as a therapeutic strategy for PCOS treatment

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Abstract

Polycystic ovary syndrome (PCOS) is frequently diagnosed hormonal disorder with reproductive and metabolic complications. The most common symptoms include cyst in ovaries, anovulation, insulin resistance, and obesity. Clomiphene citrate, an ovulating agent, is the first-line drug used to treat PCOS. We hypothesized that clomiphene citrate, by stimulating ovarian function, with krill oil used as an oil phase to improve solubility, by addressing PCOS-associated symptoms might be effective in PCOS. Hence, our goal was to target hormonal imbalance along with PCOS-associated symptoms using a single formulation. The concentration of water (X1), oil (X2), and Smix (surfactant-cosurfactant mixture) (X3) were selected as independent variables, in a simplex lattice design, from microemulsion area derived from a pseuodoternary phase diagram while the globule size (Y1) was selected as a dependent parameter. The optimized microemulsion showed good sphericity having 41 nm globule size, 0.32 poly dispersibility index and + 31 mV zeta potential. The optimized microemulsion was further evaluated in-vivo using letrozole-induced PCOS rats. Formulation treated group reversed the effect of letrozole on body weight and estrus cycle in comparison to the disease control group (p < 0.001). The formulation was also effective in reducing insulin resistance, cholesterol and serum testosterone level (p < 0.001). The in vivo results were supported by histopathological studies where the formulation-treated group showed a marked decrease in the number of cystic follicles and a remarkable increase in the number of growing follicles at variable stages, similar to the normal control group. Thus, the results confirmed that novel krill oil-based clomiphene microemulsion may become a promising therapeutic choice for the treatment of PCOS.

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All data generated or analyzed during this study are reported in this article (and its Supplementary information files) and the datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge the financial support and animal house facility provided by L.J.University, Ahmedabad, India. The authors would also like to acknowledge Gattefose, Mumbai, India, for providing various gift samples of surfactants and co-surfactants.

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  1. Department of Pharmaceutical Technology, L. J. Institute of Pharmacy, L J University, Sarkhej, Ahmedabad, Gujarat, 3882210, India

    Darshita Panchal, Tosha Pandya, Vijay Kevlani, Shreeraj Shah & Sheetal Acharya

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Contributions

Darshita Panchal: methodology and validation; Tosha Pandya: writing original draft and editing; Vijay Kevlani: animal study and editing; Dr. Shreeraj Shah: funding resources and editing; Dr. Sheetal Acharya: conceptualization, resources, supervision and project administration.

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Panchal, D., Pandya, T., Kevlani, V. et al. Development and evaluation of novel krill oil-based clomiphene microemulsion as a therapeutic strategy for PCOS treatment. Drug Deliv. and Transl. Res. 13, 2254–2271 (2023). https://doi.org/10.1007/s13346-023-01304-z

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