Next Article in Journal
Bacteria from Animals as a Pool of Antimicrobial Resistance Genes
Previous Article in Journal
Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro
Previous Article in Special Issue
Final Demonstration of the Co-Identity of Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray Analysis
Article Menu

Export Article

Open AccessArticle
Antibiotics 2017, 6(2), 11; doi:10.3390/antibiotics6020011

Erythromycin Modification That Improves Its Acidic Stability while Optimizing It for Local Drug Delivery

1
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
2
Department of Macromolecular Science and Engineering, Case Western Reserve University, 2100 Adelbert Road, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Naresh Kumar
Received: 14 December 2016 / Revised: 2 March 2017 / Accepted: 19 April 2017 / Published: 25 April 2017
(This article belongs to the Special Issue Antibiotic Synthesis)
View Full-Text   |   Download PDF [2183 KB, uploaded 25 April 2017]   |  

Abstract

The antibiotic erythromycin has limited efficacy and bioavailability due to its instability and conversion under acidic conditions via an intramolecular dehydration reaction. To improve the stability of erythromycin, several analogs have been developed—such as azithromycin and clarithromycin—which decrease the rate of intramolecular dehydration. We set out to build upon this prior work by developing a conjugate of erythromycin with improved pH stability, bioavailability, and preferential release from a drug delivery system directly at the low pH of an infection site. To develop this new drug conjugate, adamantane-1-carbohydrazide was covalently attached to erythromycin via a pH-degradable hydrazone bond. Since Staphylococcus aureus infection sites are slightly acidic, the hydrazone bond will undergo hydrolysis liberating erythromycin directly at the infection site. The adamantane group provides interaction with the drug delivery system. This local delivery strategy has the potential of reducing off-target and systemic side-effects. This work demonstrates the synthesis of a pH-cleavable, erythromycin conjugate that retains the inherent antimicrobial activity of erythromycin, has an increased hydrophobicity, and improved stability in acidic conditions; thereby enhancing erythromycin’s bioavailability while simultaneously reducing its toxicity. View Full-Text
Keywords: erythromycin; infection; pH-sensitive; pH-responsive; hydrophobic; adamantane; cyclodextrin; polymer erythromycin; infection; pH-sensitive; pH-responsive; hydrophobic; adamantane; cyclodextrin; polymer
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cyphert, E.L.; Wallat, J.D.; Pokorski, J.K.; von Recum, H.A. Erythromycin Modification That Improves Its Acidic Stability while Optimizing It for Local Drug Delivery. Antibiotics 2017, 6, 11.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Antibiotics EISSN 2079-6382 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top