Effects of Antibiotic Physicochemical Properties on Their Release Kinetics from Biodegradable Polymer Microparticles

Abstract

Purpose 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 weight percent 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 1000 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 17–49 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.

Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections

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“…Recently, it has been shown that the physicochemical characteristics of antibiotics have a strong influence on the release kinetics of antibiotics from synthetic polymers . Shah et al found that the charge and molecular weight of antibiotics influenced the incorporation into and release of antibiotics from poly (DL‐lactic‐co‐glycolic acid) microparticles. Negatively charged antibiotics were incorporated less efficiently than positively charged antibiotics, while antibiotics of higher molecular weight revealed a more sustained release.…”

A rapid, flexible method for incorporating controlled antibiotic release into porous polymethylmethacrylate space maintainers for craniofacial reconstruction

“…Qiao et al demonstrated that when 5-fluorouracil, a hydrophilic drug, is loaded into a PLGA-PEG-PLGA thermogel, release appears to be entirely diffusion-mediated; in contrast, incorporation of the hydrophobic drug indomethacin results in biphasic release characterized by early diffusion and late degradation-controlled release, similar to kinetics seen with colistin in both pure PLGA and in the triblock copolymer. 38,39 Kim et al loaded the protein drug insulin into PLGA-PEG-PLGA both with and without zinc and showed that in vitro release kinetics are likely influenced by the hydrophobicity of insulin, which causes it to partition preferentially toward the hydrophobic domains of the polymer micelles. 40 A follow-up study by Choi et al also using insulin shows a release profile that is similar to that of indomethacin and colistin, highlighting that drug hydrophobicity and partitioning are important parameters that govern release kinetics from PLGA-PEG-PLGA copolymers.…”