Steady antibiotic release from biodegradable beads in the pleural cavity: an in vitro and in vivo study

Chest. 2012 May;141(5):1197-1202. doi: 10.1378/chest.11-1254. Epub 2011 Sep 29.

Abstract

Background: Inadequate localized drug concentrations and systemic adverse effects are among the concerns when regional infections are treated with systemic antibiotics. We designed and fabricated a poly(D,L)-lactide-co-glycolide (PLGA)-based biodegradable drug delivery system and evaluated the release of antibiotics both in vitro and in vivo.

Methods: PLGA copolymer and penicillin G sodium were mixed, compressed, and sintered to fabricate biodegradable antibiotic beads. The beads were placed in phosphate-buffered saline to test the characteristics of in vitro drug release. The beads then were introduced into the pleural cavities through chest tubes of six New Zealand white rabbits. Daily pleural effusion was collected to measure the antibiotic concentration and bacterial inhibitory characteristics.

Results: Forty percent of the penicillin was released in the first day in the in vitro study. The rest of the antibiotic was then gradually released in the following 30 days. All six animals survived the experiment. The initial surge of drug release was less significant in the pleural cavity than in the phosphate-buffered saline. The drug concentrations were well above the minimum inhibitory concentration breakpoint for penicillin susceptibility throughout the study period in both in vitro (30 days) and in vivo (14 days) studies.

Conclusions: These preliminary findings demonstrated that the biodegradable PLGA antibiotic beads could achieve a fairly steady antibiotic release in the pleural cavity for at least 2 weeks. This drug delivery system may have the potential to serve as an adjuvant treatment of pleural cavity infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Biological Availability
  • Chest Tubes
  • Chromatography, High Pressure Liquid
  • Disk Diffusion Antimicrobial Tests
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Infusion Pumps, Implantable*
  • Lactic Acid*
  • Microspheres
  • Pasteurella multocida / drug effects*
  • Penicillin G / pharmacokinetics*
  • Pleural Cavity / drug effects*
  • Pleural Cavity / metabolism*
  • Pleural Cavity / microbiology
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rabbits

Substances

  • Anti-Bacterial Agents
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Penicillin G