title: Effects of antibiotic physicochemical properties on their release kinetics from biodegradable polymer microparticles.
abstract: OBJECTIVE
  This study investigated the effects of the physicochemical properties of antibiotics on the morphology, loading efficiency, size, release kinetics, and antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (MPs) at different loading percentages.
  
  
  METHODS
  Cefazolin, ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at 10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion fabrication protocol. Microparticle morphology, size, loading efficiency, release kinetics, and antibiotic efficacy were assessed.
  
  
  RESULTS
  The results from this study demonstrate that the chemical nature of loaded antibiotics, especially charge and molecular weight, influence the incorporation into and release of antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da displayed biphasic release while those with molecular weights greater than 1,000 Da displayed triphasic release kinetics. Large molecular weight drugs also had a longer delay before release than smaller molecular weight drugs. The negatively charged antibiotic cefazolin had lower loading efficiency than positively charged antibiotics. Microparticle size appeared to be mainly controlled by fabrication parameters, and partition and solubility coefficients did not appear to have an obvious effect on loading efficiency or release. Released antibiotics maintained their efficacy against susceptible strains over the duration of release. Duration of release varied between 17 and 49 days based on the type of antibiotic loaded.
  
  
  CONCLUSIONS
  The data from this study indicate that the chemical nature of antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for general prediction of loading and release kinetics.
authors.affiliation: Department of Bioengineering, Rice University, MS-142, 6100 Main St., Houston, Texas, 77005, USA.
authors.forename: Sarita R
authors.initials: SR
authors.lastname: Shah
authors.forename: Allan M
authors.initials: AM
authors.lastname: Henslee
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Spicer
authors.forename: Shun
authors.initials: S
authors.lastname: Yokota
authors.forename: Sophia
authors.initials: S
authors.lastname: Petrichenko
authors.forename: Sachin
authors.initials: S
authors.lastname: Allahabadi
authors.forename: George N
authors.initials: GN
authors.lastname: Bennett
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wong
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D007700:Kinetics; D019344:Lactic Acid; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid