Salicylate-based poly(anhydride-esters) were synthesized via two different methods, melt-condensation and solution polymerization, and the resulting polymers were compared. Acetylsalicylic acid was used as a model compound to mimic the active polymer chain-ends during melt-condensation, and formed a low-molecular-weight (<1500) polymer when subjected to melt-condensation polymerization conditions. The polymers and model compounds were analyzed by NMR ((1)H and (13)C) and IR spectroscopies to elucidate the structures. Spectroscopic analysis revealed the formation of a thermodynamically stable salicylate ester via salicylate-anhydride rearrangement during melt-condensation polymerization, which did not occur during solution polymerization. The salicylate-based poly(anhydride-esters) undergo a thermodynamic rearrangement during melt-condensation polymerization that is not observed for solution polymerization.

A polymer blend consisting of antimicrobials (chlorhexidine, clindamycin, and minocycline) physically admixed at 10% by weight into a salicylic acid-based poly (anhydride-ester) (SA-based PAE) was developed as an adjunct treatment for periodontal disease. The SA-based PAE/ antimicrobial blends were characterized by multiple methods, including contact angle measurements and differential scanning calorimetry. Static contact angle measurements showed no significant differences in hydrophobicity between the polymer and antimicrobial matrix surfaces. Notable decreases in the polymer glass transition temperature (T g ) and the antimicrobials' melting points (T m ) were observed indicating that the antimicrobials act as plasticizers within the polymer matrix. In vitro drug release of salicylic acid from the polymer matrix and for each physically admixed antimicrobial was concurrently monitored by high pressure liquid chromatography during the course of polymer degradation and erosion. Although the polymer/antimicrobial blends were immiscible, the initial 24 h of drug release correlated to the erosion profiles. The SA-based PAE/antimicrobial blends are being investigated as an improvement on current localized drug therapies used to treat periodontal disease.

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.

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<div>Abstract<p><b>Background:</b> Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden.</p><p><b>Methods:</b> HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma <i>in situ</i> (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected.</p><p><b>Results:</b> From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; <i>P</i> < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (<i>P</i> < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; <i>P</i> < 0.001).</p><p><b>Conclusions:</b> Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities.</p><p><b>Impact:</b> Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. <i>Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR</i>.</p></div>