Optimization, characterization and in vivo evaluation of mupirocin nanocrystals for topical administration
Muna B Najm1, Mutasem Rawas-Qalaji1, Nouran H Assar2
1Department of Pharmaceutics & Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
Abstract:
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.
Insights
Nanocrystallization enhanced mupirocin (MP) efficacy against MRSA skin infections. Mupirocin-nanocrystals (MP-NC) showed improved solubility, dissolution, and skin penetration, leading to faster wound healing in vivo.
Area of Science:
- Pharmaceutical Sciences
- Nanotechnology
- Dermatology
Background:
- Topical antibiotic treatment for skin infections, especially MRSA, is hindered by bacterial biofilms and antimicrobial resistance.
- Mupirocin (MP) efficacy is limited by poor water solubility and increasing bacterial resistance.
- Nanocrystallization offers a strategy to enhance the therapeutic performance of poorly soluble drugs.
Purpose of the Study:
- To improve the therapeutic efficacy of mupirocin for skin infections by modifying its physicochemical properties via nanocrystallization.
- To develop and optimize mupirocin-nanocrystals (MP-NC) for enhanced topical delivery and antimicrobial activity.
Main Methods:
- Mupirocin-nanocrystals (MP-NC) were prepared using a nanoprecipitation technique and optimized via a D-optimal response surface design.
- Characterization included particle size, polydispersity, solubility, and dissolution rate.
- In vitro, ex vivo (pig ear skin), microbiological (MIC/MBC), and in vivo (rat burn wound model) studies were conducted.
Main Results:
- Optimized MP-NC exhibited ultra-small, monodisperse spherical particles (70 nm diameter, 0.2 PDI).
- MP-NC demonstrated a 10-fold increase in saturation solubility and a 9-fold increase in dissolution rate.
- Ex vivo studies showed a 2-fold increase in dermal deposition, with significant drug presence at 500 µm depth.
- Microbiological assays revealed a 16-fold reduction in MIC and MBC.
- In vivo studies demonstrated rapid and complete healing of infected burn wounds in rats treated with MP-NC cream compared to a marketed product.
Conclusions:
- Nanocrystallization significantly enhanced the solubility, dissolution, and antimicrobial efficacy of mupirocin.
- MP-NC formulations demonstrated improved skin permeation and deposition, suggesting enhanced local drug delivery.
- MP-NC cream represents a promising therapeutic approach for treating challenging skin infections, including those caused by MRSA.
