Anti-infectives in drug delivery-overcoming the Gram-negative bacterial cell envelope

Florian Graef, Sarah Gordon, Claus Michael Lehr

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

9 Citations (Scopus)


Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide. Thus, new approaches which allow for more comprehensive characterization of anti-infective permeation processes (and as such, would be usable as screening methods in early drug discovery and development) are desperately needed. Furthermore, delivery methods or technologies capable of enhancing anti-infective permeation into or across the bacterial cell envelope are required. In this respect, particle-based carrier systems have already been shown to provide the opportunity to overcome compound-related difficulties and allow for targeted delivery. In addition, formulations combining efflux pump inhibitors or antimicrobial peptides with anti-infectives show promise in the restoration of antibiotic activity in resistant bacterial strains. Despite considerable progress in this field however, the design of carriers to specifically enhance transport across the bacterial envelope or to target difficult-to-treat (e.g., intracellular) infections remains an urgently needed area of improvement. What follows is a summary and evaluation of the state of the art of both bacterial permeation models and advanced anti-infective formulation strategies, together with an outlook for future directions in these fields.

Original languageEnglish
Title of host publicationHow to Overcome the Antibiotic Crisis
Subtitle of host publicationFacts, Challenges, Technologies and Future Perspectives
EditorsMarc Stadler, Petra Dersch
Number of pages22
ISBN (Electronic)9783319492841
ISBN (Print)9783319492827, 9783319841212
Publication statusPublished - 2 Jan 2017

Publication series

NameCurrent Topics in Microbiology and Immunology
ISSN (Print)0070-217X
ISSN (Electronic)2196-9965

Bibliographical note

Publisher Copyright:
© Springer International Publishing AG 2016.


  • Outer Membrane
  • Cell Envelope
  • Envelope Structure
  • Permeation Process
  • Efflux Pump Inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)


Dive into the research topics of 'Anti-infectives in drug delivery-overcoming the Gram-negative bacterial cell envelope'. Together they form a unique fingerprint.

Cite this