Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD)
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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/976 |
| _version_ | 1797496717660127232 |
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| author | Lakshmi Pulakat Howard H. Chen Madhavi P. Gavini Lauren A. Ling Yinian Tang Alexander Mehm Gregory L. Martin Corinna N. Beale Brian P. Mooney Hongmin Sun |
| author_facet | Lakshmi Pulakat Howard H. Chen Madhavi P. Gavini Lauren A. Ling Yinian Tang Alexander Mehm Gregory L. Martin Corinna N. Beale Brian P. Mooney Hongmin Sun |
| author_sort | Lakshmi Pulakat |
| collection | DOAJ |
| description | 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 <i>E. coli</i> and live tissue imaging, we show that (1) the extent of attenuation of deep-skin <i>E. coli</i> 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. |
| first_indexed | 2024-03-10T03:07:34Z |
| format | Article |
| id | doaj.art-73881ee573a04dbd861acb85661ecadc |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:07:34Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-73881ee573a04dbd861acb85661ecadc2023-11-23T12:37:31ZengMDPI AGPharmaceutics1999-49232022-04-0114597610.3390/pharmaceutics14050976Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD)Lakshmi Pulakat0Howard H. Chen1Madhavi P. Gavini2Lauren A. Ling3Yinian Tang4Alexander Mehm5Gregory L. Martin6Corinna N. Beale7Brian P. Mooney8Hongmin Sun9Tufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USATufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USADroplette Inc., Boston, MA 02108, USATufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USATufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USATufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USATufts Medical Center, Molecular Cardiology Research Institute, Boston, MA 02111, USASchool of Medicine, Tufts University, Boston, MA 02111, USACharles W. Gehrke Proteomics Center, Division of Biochemistry, University of Missouri, Columbia, MO 65211, USADivision of Cardiovascular Medicine, Department of Medicine, University of Missouri, Columbia, MO 65211, USAWound 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 <i>E. coli</i> and live tissue imaging, we show that (1) the extent of attenuation of deep-skin <i>E. coli</i> 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.https://www.mdpi.com/1999-4923/14/5/976transdermal deliveryDroplette micromist technology device (DMTD)multidrug resistant bacteriacolistin methanesulfonatevancomycin<i>E. coli</i> |
| spellingShingle | Lakshmi Pulakat Howard H. Chen Madhavi P. Gavini Lauren A. Ling Yinian Tang Alexander Mehm Gregory L. Martin Corinna N. Beale Brian P. Mooney Hongmin Sun Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) Pharmaceutics transdermal delivery Droplette micromist technology device (DMTD) multidrug resistant bacteria colistin methanesulfonate vancomycin <i>E. coli</i> |
| title | Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) |
| title_full | Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) |
| title_fullStr | Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) |
| title_full_unstemmed | Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) |
| title_short | Transdermal Delivery of High Molecular Weight Antibiotics to Deep Tissue Infections via Droplette Micromist Technology Device (DMTD) |
| title_sort | transdermal delivery of high molecular weight antibiotics to deep tissue infections via droplette micromist technology device dmtd |
| topic | transdermal delivery Droplette micromist technology device (DMTD) multidrug resistant bacteria colistin methanesulfonate vancomycin <i>E. coli</i> |
| url | https://www.mdpi.com/1999-4923/14/5/976 |
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