Optimization, characterization and in vivo evaluation of mupirocin nanocrystals for topical administration
Copyright © 2022. Published by Elsevier B.V..
Treatment of infectious skin conditions resulting from wounds and burns with topical antibiotics is challenging, particularly those caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). This is due to the formation of bacterial biofilms characterized by antimicrobial resistance. Mupirocin (MP), a widely used topical antibiotic, is active against gram-positive bacteria including MRSA. However, MP suffers from sub-optimal therapeutic efficacy due to its poor water-solubility and the significant rise in MP-resistant S. aureus. In this study, the physico-chemical characteristics of MP were modified through nanocrystallization to improve its therapeutic efficacy for the treatment of skin infections. Mupirocin-nanocrystals (MP-NC) were prepared using a nanoprecipitation technique and optimized using a D-optimal response surface design. The optimization of MP-NC produced ultra-small monodisperse spherical particles with a mean diameter of 70 nm and a polydispersity index of 0.2. The design resulted in two optimal MP-NC formulations that were evaluated by performing series of in vitro, ex vivo, microbiological, and in vivo studies. In-vitro results showed a 10-fold increase in the saturation solubility and a 9-fold increase in the dissolution rate of MP-NC. Ex vivo permeation studies, using pig ears skin, showed a 2-fold increase in the dermal deposition of MP-NC with the highest drug deposition occurring at 500-µm skin depth. Moreover, the optimal MP-NC formulations were lyophilized and incorporated into a 2% w/w cream. Microbiological studies revealed a 16-fold decrease in the minimum inhibitory concentration and the minimum bactericidal concentration of MP-NC. In vivo studies, using a rat excision burn wound model, demonstrated rapid and complete healing of infected burn wounds in rats treated with MP-NC cream in comparison to marketed Avoban ointment. Our results suggest that nanocrystallization of MP may provide an avenue through which higher levels of a topically applied MP can be permeated into the skin to reach relevant infectious areas and exert potential local antibacterial effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:176 |
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| Enthalten in: |
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences - 176(2022) vom: 01. Sept., Seite 106251 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Najm, Muna B [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 03.08.2022 Date Revised 03.08.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejps.2022.106251 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Treatment of infectious skin conditions resulting from wounds and burns with topical antibiotics is challenging, particularly those caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). This is due to the formation of bacterial biofilms characterized by antimicrobial resistance. Mupirocin (MP), a widely used topical antibiotic, is active against gram-positive bacteria including MRSA. However, MP suffers from sub-optimal therapeutic efficacy due to its poor water-solubility and the significant rise in MP-resistant S. aureus. In this study, the physico-chemical characteristics of MP were modified through nanocrystallization to improve its therapeutic efficacy for the treatment of skin infections. Mupirocin-nanocrystals (MP-NC) were prepared using a nanoprecipitation technique and optimized using a D-optimal response surface design. The optimization of MP-NC produced ultra-small monodisperse spherical particles with a mean diameter of 70 nm and a polydispersity index of 0.2. The design resulted in two optimal MP-NC formulations that were evaluated by performing series of in vitro, ex vivo, microbiological, and in vivo studies. In-vitro results showed a 10-fold increase in the saturation solubility and a 9-fold increase in the dissolution rate of MP-NC. Ex vivo permeation studies, using pig ears skin, showed a 2-fold increase in the dermal deposition of MP-NC with the highest drug deposition occurring at 500-µm skin depth. Moreover, the optimal MP-NC formulations were lyophilized and incorporated into a 2% w/w cream. Microbiological studies revealed a 16-fold decrease in the minimum inhibitory concentration and the minimum bactericidal concentration of MP-NC. In vivo studies, using a rat excision burn wound model, demonstrated rapid and complete healing of infected burn wounds in rats treated with MP-NC cream in comparison to marketed Avoban ointment. Our results suggest that nanocrystallization of MP may provide an avenue through which higher levels of a topically applied MP can be permeated into the skin to reach relevant infectious areas and exert potential local antibacterial effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antibacterial activity | |
| 650 | 4 | |a Dermal drug delivery | |
| 650 | 4 | |a Ex vivo studies | |
| 650 | 4 | |a Mupirocin | |
| 650 | 4 | |a Nanocrystals | |
| 650 | 4 | |a Rat excision burn wound infection model | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Mupirocin |2 NLM | |
| 650 | 7 | |a D0GX863OA5 |2 NLM | |
| 700 | 1 | |a Rawas-Qalaji, Mutasem |e verfasserin |4 aut | |
| 700 | 1 | |a Assar, Nouran H |e verfasserin |4 aut | |
| 700 | 1 | |a Yahia, Rania |e verfasserin |4 aut | |
| 700 | 1 | |a Hosary, Rania El |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Iman S |e verfasserin |4 aut | |
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