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Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist
Lakshmi Pulakat1,2,3, Howard H Chen1,2, Madhavi P Gavini4
1Tufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USA.
Abstract:
Wound infection by multidrug-resistant (MDR) bacteria is a major disease burden. Systemic administration of broad-spectrum antibiotics colistin methanesulfonate (CMS) and vancomycin are the last lines of defense against deep wound infections by MDR bacteria. However, systemic administration of CMS and vancomycin are linked to life-threatening vital organ damage. Currently there are no effective topical application strategies to deliver these high molecular weight antibiotics across the stratum corneum. To overcome this difficulty, we tested if high molecular weight antibiotics delivered by Droplette micromist technology device (DMTD), a transdermal delivery device that generates a micromist capable of packaging large molecules, could attenuate deep skin tissue infections. Using green fluorescent protein-tagged E. coli and live tissue imaging, we show that (1) the extent of attenuation of deep-skin E. coli infection was similar when treated with topical DMTD- or systemic IP (intraperitoneal)-delivered CMS; (2) DMTD-delivered micromist did not spread the infection deeper; (3) topical DMTD delivery and IP delivery resulted in similar levels of vancomycin in the skin after a 2 h washout period; and (4) IP-delivered vancomycin was about 1000-fold higher in kidney and plasma than DMTD-delivered vancomycin indicating systemic toxicity. Thus, topical DMTD delivery of these antibiotics is a safe treatment for the difficult-to-treat deep skin tissue infections by MDR bacteria.
Insights
Topical delivery of colistin methanesulfonate (CMS) and vancomycin using a micromist device safely treats multidrug-resistant bacterial wound infections. This method avoids systemic toxicity associated with conventional antibiotic administration.
Area of Science:
- Microbiology
- Dermatology
- Drug Delivery Systems
Background:
- Wound infections by multidrug-resistant (MDR) bacteria pose a significant health challenge.
- Systemic administration of last-resort antibiotics like colistin methanesulfonate (CMS) and vancomycin can cause severe organ damage.
- Effective topical delivery of these high-molecular-weight antibiotics across the stratum corneum is currently lacking.
Purpose of the Study:
- To evaluate the efficacy and safety of delivering CMS and vancomycin via a Droplette micromist technology device (DMTD) for treating deep skin tissue infections.
- To compare topical DMTD delivery with systemic intraperitoneal (IP) delivery of these antibiotics.
Main Methods:
- Utilized green fluorescent protein-tagged E. coli to model deep skin infections.
- Employed live tissue imaging to assess infection attenuation.
- Quantified antibiotic levels in skin, kidney, and plasma after topical DMTD and systemic IP administration.
Main Results:
- Topical DMTD delivery of CMS showed comparable infection attenuation to systemic IP delivery.
- DMTD-delivered micromist did not exacerbate deeper infection spread.
- Similar vancomycin levels were found in skin tissue after 2 hours for both topical and systemic delivery.
- Systemic IP delivery resulted in significantly higher antibiotic concentrations in kidney and plasma, indicating potential toxicity.
Conclusions:
- Topical DMTD delivery of CMS and vancomycin offers a safe and effective alternative for treating deep skin tissue infections caused by MDR bacteria.
- This transdermal delivery approach mitigates the risk of systemic toxicity associated with conventional antibiotic administration.
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