Hyaluronic acid derivatives and its polyelectrolyte complexes with gentamicin as a delivery system for antibiotics

Repeated administration of gentamicin (Gen) is often necessary to have efficacious pharmacokinetics in both infection prophylaxis and treatment. In order to increase the half-time of Gen sulfate and minimize the dosage, the antibiotic can be grafted to polymers as a prodrug or encapsulated within polymers. Gen is positively charged and can interact with negatively charged macromolecules to form polyelectrolyte complexes (PECs). The complexation of Gen with hyaluronic acid (HA) was investigated here. Subsequently, several HA conjugates were prepared and screened for their thermo-responsive behavior and their ability to form PECs with Gen. PEC formation with HA poly(N-isopropylacrylamide) yields an injectable formulation, which precipitates out of solution to form microscopic or macroscopic gels, depending on its concentration, at temperatures higher than the lower critical solution temperature