Water-borne, underwater adhesives were created by complex coacervation of synthetic copolyelectrolytes that mimic the proteins of the natural underwater adhesive of the sandcastle worm. To increases bond strengths, a second polymer network was created within crosslinked coacervate network by entrapping polyethylene glycol diacrylate (PEG-dA) monomers in the coacervate phase. Simultaneous polymerization of PEG-dA and crosslinking of the coacervate network resulted in maximum shear bond strengths of ∼ 1.2 MPa. Approximately 40% of the entrapped PEG-dA polymerized based on attenuated total reflectance-Fourier transform infrared spectroscopy. The monomer-filled coacervate had complex flow behavior, thickening at low shear rates, then thinning suddenly with a 16-fold drop in viscosity at shear rates near 6 s-1. The microscale structure of the complex coacervates resembled a three-dimensional porous network of interconnected tubules. The sharp shear thinning behavior is conceptualized as a structural reorganization between the interspersed phases of the complex coacervate. The bond strength and complex fluid behavior of the monomer-filled coacervates have important implications for medical applications of the adhesives.

A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10 7 SCC-38 cells, groups of 5 nu/nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-transretinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RARR, RXRR, and RXR were similar in the two cell lines, while RAR expression was higher in SCC-2 over SCC-38, and RARγ expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

Periodate oxidation of carbohydrates with vicinal hydroxyl groups and aromatic ortho-dihydroxyphenyl groups has been employed extensively to initiate crosslinking or conjugation reactions in adhesive biomaterials. Periodate forms stable tridentate complexes with carbohydrates containing three appropriately configured hydroxyls, such as 1,2-O-Isopropylidene-a-D-glucofuranose, that are not appreciably oxidized relative to carbohydrates with vicinal hydroxyls and ortho-dihydroxyphenyl groups. In the presence of 1,2-O-Isopropylidene-a-D-glucofuranose the rate of periodate oxidation of dihydroxy containing compounds is controlled by the rates of association and dissociation of the periodate-carbohydrate complex. By varying the ratio of 1,2-O-Isopropylidene-a-D-glucofuranose to periodate the curing rate of adhesive complex coacervates was varied over a wide range.