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Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
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The parenteral route is a critical method of drug administration. It delivers compounds directly into the systemic circulation and bypasses the gastrointestinal tract. This approach is particularly advantageous for drugs that exhibit poor absorption or instability when administered orally.
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Related Experiment Video

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Advanced delivery systems for peptide antibiotics.

Angela Cesaro1, Shuangzhe Lin1, Norbert Pardi2

  • 1Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, United States.

Advanced Drug Delivery Reviews
|February 21, 2023
PubMed
Summary

Antimicrobial peptides show potential against resistant infections but face delivery challenges. This review explores advanced drug delivery systems to enhance peptide antibiotic efficacy and safety.

Keywords:
Antibiotic resistanceAntimicrobial peptidesCell-based delivery systemsDrug-deliveryInfectious diseasesmRNA-lipid nanoparticle-based therapy

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Area of Science:

  • Biochemistry and Molecular Biology
  • Drug Delivery Systems
  • Infectious Diseases

Background:

  • Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics for combating multidrug-resistant infections.
  • AMPs face limitations due to protease susceptibility and potential cytotoxicity, hindering their clinical application.
  • Effective drug delivery is crucial for overcoming these limitations and optimizing AMP therapeutic profiles.

Purpose of the Study:

  • To review current drug delivery strategies for antimicrobial peptides.
  • To highlight methods that improve the pharmacokinetic and pharmacodynamic properties of peptide-based antibiotics.
  • To discuss the potential of various formulations in addressing AMP limitations.

Main Methods:

  • Review of existing literature on peptide drug delivery systems.
  • Categorization of delivery methods including nanoparticles, hydrogels, functionalized surfaces, and nucleic acid-based systems.
  • Analysis of formulation approaches for enhancing AMP stability and targeted delivery.

Main Results:

  • Various advanced delivery systems, including lipid and polymeric nanoparticles, hydrogels, functionalized surfaces, and DNA/RNA-based systems, have been developed for AMPs.
  • These systems demonstrate potential in protecting AMPs from degradation and reducing off-target effects.
  • Formulation strategies can significantly improve the therapeutic index of peptide antibiotics.

Conclusions:

  • Advanced drug delivery systems are essential for realizing the full therapeutic potential of antimicrobial peptides.
  • Tailored delivery strategies can overcome key challenges associated with AMPs, such as protease instability and cytotoxicity.
  • Continued research into novel delivery platforms will be critical for developing effective peptide-based treatments for resistant infections.