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Dual delivery systems combining nanocrystals and dissolving microneedles for improved local vaginal delivery of fluconazole

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Abstract

Fluconazole (FLZ) has been widely used in the treatment of infection caused by Candida albicans, including the treatment of vulvovaginal candidiasis (VVC). However, when delivered orally, FLZ faces numerous limitations due to its poor solubility and undergoes the symptoms of first-pass metabolism. In this study, we developed the combinatorial approach of nanocrystals (NCs) and dissolving microneedles (DMNs) for effective local vaginal delivery of FLZ. The formulation containing 1.0% w/v PVA as stabilizer with 12 h of milling time process was found to be an optimal combination to fabricate FLZ as NCs (FLZ-NCs) with optimum size particle and PDI value (less than 0.25). Furthermore, the in vitro release study also showed a superior percentage of FLZ release up to 89.51 ± 7.52%. In combination with the DMNs, the FLZ recovery was 96.45 ± 2.38% with the insertion percentage in average of 76.14 ± 2.28% and height decreased percentage was only 7.53 ± 0.56%. Moreover, the ex vivo investigation and anti-candidiasis activity of DMNs-FLZ-NCs in vaginal model showed better results compared to other conventional preparations, such as film patch and hydrogel containing FLZ.

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Funding

This research was supported by Hasanuddin University through “Penelitian Fundamental Kolaboratif” program.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia

    Anugerah Yaumil Ramadhani Aziz, Ulfah Mahfufah, Nor Atikah Syahirah, Rangga Meidianto Asri & Andi Dian Permana

  2. Department of Pharmacology-Toxicology, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia

    Habibie

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, 90245, Indonesia

    Risfah Yulianty

  4. Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Cibinong, 16911, Indonesia

    Ria Fajarwati Kastian

  5. Department of Physics, Institut Pertanian Bogor, Bogor, Indonesia

    Yessie Widya Sari

  6. Department of Pharmacy, Universitas Islam Indonesia, Yogyakarta, 55584, Indonesia

    Lutfi Chabib

  7. Faculty of Pharmacy, Universitas Muhammadiyah Kalimantan Timur, Samarinda, 75124, Indonesia

    Hasyrul Hamzah

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  1. Anugerah Yaumil Ramadhani Aziz
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Contributions

A.Y.R.A.: conceptualization, methodology, writing—original draft, review and editing, and validation; U.M.: investigation and data curation; N.A.S.: investigation and data curation; H.: review and editing and project administration; R.M.A.: methodology, investigation, data curation, and formal analysis; R.Y.: review and editing; R.F.K.: review and editing; Y.W.S.: investigation, data curation, and formal analysis; L.C.: investigation, data curation, and formal analysis; H.H.: investigation, data curation, and formal analysis; A.D.P.: conceptualization, methodology, writing—original draft, investigation, data curation, and visualization.

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Correspondence to Andi Dian Permana.

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Aziz, A.Y.R., Mahfufah, U., Syahirah, N.A. et al. Dual delivery systems combining nanocrystals and dissolving microneedles for improved local vaginal delivery of fluconazole. Drug Deliv. and Transl. Res. 14, 1678–1692 (2024). https://doi.org/10.1007/s13346-023-01483-9

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