Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment

Bacterial vaginosis is an infectious disease that has significantly affected women’s health. Metronidazole has been widely used as a drug for treating bacterial vaginosis. Nevertheless, the currently available therapies have been found to be inefficient and inconvenient. Here, we developed the combi...

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Main Authors: Andi Dian Permana, Rangga Meidianto Asri, Muhammad Nur Amir, Achmad Himawan, Andi Arjuna, Nana Juniarti, Rifka Nurul Utami, Sandra Aulia Mardikasari
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/5/1529
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author Andi Dian Permana
Rangga Meidianto Asri
Muhammad Nur Amir
Achmad Himawan
Andi Arjuna
Nana Juniarti
Rifka Nurul Utami
Sandra Aulia Mardikasari
author_facet Andi Dian Permana
Rangga Meidianto Asri
Muhammad Nur Amir
Achmad Himawan
Andi Arjuna
Nana Juniarti
Rifka Nurul Utami
Sandra Aulia Mardikasari
author_sort Andi Dian Permana
collection DOAJ
description Bacterial vaginosis is an infectious disease that has significantly affected women’s health. Metronidazole has been widely used as a drug for treating bacterial vaginosis. Nevertheless, the currently available therapies have been found to be inefficient and inconvenient. Here, we developed the combination approach of gel flake and thermoresponsive hydrogel systems. The gel flakes were prepared using gellan gum and chitosan, showing that the incorporation of metronidazole was able to provide a sustained release pattern for 24 h with an entrapment efficiency of >90%. Moreover, the gel flakes were incorporated into Pluronics-based thermoresponsive hydrogel using the combination of Pluronic F127 and F68. The hydrogels were found to exhibit the desired thermoresponsive properties, showing sol-gel transition at vaginal temperature. Following the addition of sodium alginate as a mucoadhesive agent, the hydrogel was retained in the vaginal tissue for more than 8 h, with more than 5 mg of metronidazole retained in the ex vivo evaluation. Finally, using the bacterial vaginosis infection model in rats, this approach could decrease the viability of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> with reduction percentages of more than 95% after 3 days of treatment, with the healing ability similar to normal vaginal tissue. In conclusion, this study offers an effective approach for the treatment of bacterial vaginosis.
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spelling doaj.art-f20095bed6ef47b8b9b8c78c8ae05d342023-11-18T02:52:54ZengMDPI AGPharmaceutics1999-49232023-05-01155152910.3390/pharmaceutics15051529Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis TreatmentAndi Dian Permana0Rangga Meidianto Asri1Muhammad Nur Amir2Achmad Himawan3Andi Arjuna4Nana Juniarti5Rifka Nurul Utami6Sandra Aulia Mardikasari7Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaDepartment of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, IndonesiaBacterial vaginosis is an infectious disease that has significantly affected women’s health. Metronidazole has been widely used as a drug for treating bacterial vaginosis. Nevertheless, the currently available therapies have been found to be inefficient and inconvenient. Here, we developed the combination approach of gel flake and thermoresponsive hydrogel systems. The gel flakes were prepared using gellan gum and chitosan, showing that the incorporation of metronidazole was able to provide a sustained release pattern for 24 h with an entrapment efficiency of >90%. Moreover, the gel flakes were incorporated into Pluronics-based thermoresponsive hydrogel using the combination of Pluronic F127 and F68. The hydrogels were found to exhibit the desired thermoresponsive properties, showing sol-gel transition at vaginal temperature. Following the addition of sodium alginate as a mucoadhesive agent, the hydrogel was retained in the vaginal tissue for more than 8 h, with more than 5 mg of metronidazole retained in the ex vivo evaluation. Finally, using the bacterial vaginosis infection model in rats, this approach could decrease the viability of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> with reduction percentages of more than 95% after 3 days of treatment, with the healing ability similar to normal vaginal tissue. In conclusion, this study offers an effective approach for the treatment of bacterial vaginosis.https://www.mdpi.com/1999-4923/15/5/1529metronidazolebacterial vaginosisgel flakesthermoresponsive hydrogelsmucoadhesive
spellingShingle Andi Dian Permana
Rangga Meidianto Asri
Muhammad Nur Amir
Achmad Himawan
Andi Arjuna
Nana Juniarti
Rifka Nurul Utami
Sandra Aulia Mardikasari
Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
Pharmaceutics
metronidazole
bacterial vaginosis
gel flakes
thermoresponsive hydrogels
mucoadhesive
title Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
title_full Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
title_fullStr Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
title_full_unstemmed Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
title_short Development of Thermoresponsive Hydrogels with Mucoadhesion Properties Loaded with Metronidazole Gel-Flakes for Improved Bacterial Vaginosis Treatment
title_sort development of thermoresponsive hydrogels with mucoadhesion properties loaded with metronidazole gel flakes for improved bacterial vaginosis treatment
topic metronidazole
bacterial vaginosis
gel flakes
thermoresponsive hydrogels
mucoadhesive
url https://www.mdpi.com/1999-4923/15/5/1529
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