Biodegradable polyphosphazenes containing antibiotics: synthesis, characterization, and hydrolytic release behavior

Abstract

Novel polyphosphazenes containing the fluoroquinolone antibiotic substituents, ciprofloxacin or norfloxacin, were synthesized and characterized. Nano/microfibers of several selected polymers were prepared by an electrospinning technique. The sensitivity to hydrolysis, pH behavior, and antibiotic release profile of all the polymers as films and the selected polymers as nano/microfibers were investigated. The hydrolysis release behavior was further studied by an in vitro antibacterial test against E. coli. Protection and deprotection reactions of ciprofloxacin and norfloxacin were carried out before and after polymer synthesis to prevent cross-linking of multi-functional reagents with polymers. No more than 25 mol% of antibiotics can be introduced to poly(dichlorophosphazene) which was synthesized by a thermal ring opening polymerization of hexachlorocyclotriphosphazene. Various amino acid ethyl esters (glycine, alanine, and phenylalanine) were linked to the polymers as co-substituents to increase the solubility as well as to control the rate of antibiotic release. Depending on the polymer compositions, 5–23% weight loss and 4–30% antibiotic release were observed in a six week hydrolysis study at 37 °C. The corresponding nano/microfibers showed a much faster degradation and antibiotics release due to a substantially larger surface area. The in vitro antibacterial tests showed an antibacterial effect as long as ciprofloxacin or norfloxacin was released from the polymers. Meanwhile, all the polymers gave a near-neutral hydrolysis environment with the pH ranging from 5.9 to 6.8.