Almudena Prudencio

A Novel Approach for Incorporation of Mono-Functional Bioactive Phenols into Polyanhydrides

Antiseptics based on phenol and phenolic derivatives were chemically incorporated into polyanhydrides as pendant groups via ester linkages. Polyanhydrides with antiseptic loadings of 46-58 wt.-% were obtained with molecular weights ranging from 9 400-23 000. In general, polymers with the bulkier antiseptics were more difficult to polymerize and yielded lower molecular weights. All polyanhydrides were amorphous with glass transition temperatures ranging from 27-58 °C. Polymers were deemed noncytotoxic after culturing L929 mouse fibroblast cells in media containing the polymers at two concentrations (0.10 and 0.01 mg · mL(-1) ) over three days. In summary, mono-functional bioactives can be chemically incorporated into noncytotoxic polyanhydrides.

Characterization and in vitro degradation of salicylate-derived poly(anhydride-ester microspheres).

The aim of this study was to investigate how glass transition temperature (Tg) influenced polymer microsphere formation and degradation of three chemically, similar novel salicylatebased poly(anhydride-esters): poly[1,6-bis(o-carboxyphenoxy)hexanoate] (CPH), Tg = 59°C; poly[1,8-bis(o-carboxyphenoxy)octanoate] (CPO), Tg = 30°C; and poly[1,10-bis(ocarboxyphenoxy) decanoate] (CPD), Tg = 27°C. Microspheres of these polymers were prepared using a modified oil-in-water solvent evaporation method and processed by either resuspension or washed by centrifugation. The morphology of the microspheres determined by scanning electron microscopy (SEM) revealed that an extra washing step appears to increase aggregation as the Tg decreases; whereas only limited aggregation occurred in the polymer with the lowest Tg, CPD, in those not washed by centrifugation. Residual polyvinyl alcohol apparently affected the drug release rates from the microspheres by a stabilization process that produced an 8 h lag time and a 5% decrease in the amount of drug released over a 7 day period compared to microspheres washed free of PVA. These results demonstrate that salicylate-based poly(anhydride-esters) with sufficiently high Tgs, can be processed into microspheres that release salicylate over a time period amenable for drug delivery applications.

Phenolic Acid-based Poly(anhydride-esters) as Antioxidant Biomaterials

Poly(anhydride-esters) comprised of naturally occurring, non-toxic phenolic acids, namely syringic and vanillic acid, with antioxidant properties were prepared via solution polymerization methods. Polymer and polymer precursor physiochemical properties were characterized, including polymer molecular weight and thermal properties. In vitro release studies illustrated that polymer hydrolytic degradation was influenced by relative hydrophobicity and degree of methoxy substitution of the phenolic acids. Further, the released phenolic acids were found to maintain antioxidant potency relative to free phenolic acid controls as determined by a 2,2-diphenyl-1-picrylhydrazyl assay. Polymer cytotoxicity was assessed with L929 fibroblasts in polymer-containing media; appropriate cell morphology and high fibroblast proliferation were obtained for the polymers at the lower concentrations. These polymers deliver non-cytotoxic levels of naturally occurring antioxidants, which could be efficacious in topical delivery of antioxidant therapies.

Polymeric prodrugs of ampicillin as antibacterial coatings

A novel ampicillin prodrug containing two carboxylic acid functionalities was synthesized by reacting ampicillin with acyl chloride in the presence of base. This prodrug was subsequently converted into a poly(anhydride-amide) via solution polymerization. The polymer, which chemically incorporates the ampicillin prodrug into the polymeric backbone, was developed as a film to prevent infections associated with medical devices by controlled, localized release of antimicrobials. The robust polymer coatings exhibiting strong adhesion to stainless steel were produced under elevated temperature and reduced pressure. The in vitro hydrolytic degradation of the polymer into the ampicillin prodrug was measured and the antibacterial activity of polymer-derived coatings was examined using a Gram-positive bacterium, Staphylococcus aureus. Furthermore, the polymer cytotoxicity was screened using fibroblasts. The ampicillin prodrug demonstrated antibacterial activity and the polymer demonstrated no cytotoxic effects on fibroblasts. Based on these results, the biodegradation of the antimicrobial-based poly(anhydride-amide) into the prodrug displays substantial promise as an implant or implant coating to reduce device failure resulting from bacterial infections.