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Bacterially sensitive nanoparticle-based dissolving microneedles of doxycycline for enhanced treatment of bacterial biofilm skin infection: A proof of concept study.

Authors
  • Dian Permana, Andi1
  • Mir, Maria2
  • Utomo, Emilia3
  • Donnelly, Ryan F4
  • 1 School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast. BT9 7BL, UK; Department of Pharmaceutics, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia. , (Indonesia)
  • 2 School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast. BT9 7BL, UK; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. , (Pakistan)
  • 3 School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast. BT9 7BL, UK.
  • 4 School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast. BT9 7BL, UK. Electronic address: [email protected]
Type
Published Article
Journal
International journal of pharmaceutics
Publication Date
Mar 09, 2020
Pages
119220–119220
Identifiers
DOI: 10.1016/j.ijpharm.2020.119220
PMID: 32165225
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The presence of bacterial biofilms in wounds is a main issue in the healing process. Conventional therapy of bacterial biofilms is hampered by the poor penetration of antibacterial agents through the physical barrier on the infected skin and the non-specific target of antibacterial agents. Here, we present a combination approach of bacterial sensitive nanoparticles (NPs) and dissolving microneedles (MNs) of doxycycline (DOX) for improved biofilm penetration and specifically delivering DOX to the infection site. The NPs were prepared from poly(lactic-co-glycolic acid) and poly (Ɛ-caprolactone) decorated with chitosan. The release of DOX was improved with the presence of bacterial producing biofilm up to 7-fold. The incorporation of these NPs into dissolving MNs was able to significantly enhance the dermatokinetic profiles of DOX, indicated by higher retention time compared to needle-free patches. Importantly, the antibiofilm activity in ex vivo biofilm model showed that after 48 h, the bacterial bioburdens decreased up to 99.99% following the application of this approach. The results presented here assist as proof of principle for the improvement of dermatokinetic profiles and antibiofilm activities of DOX, following its formulation into bacterial sensitive NPs and deliveryviaMN. Future studies must explore in vivo efficacy in a suitable animal model. Copyright © 2020. Published by Elsevier B.V.

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