Photopolymerized Cross-Linked Thiol–Ene Polyanhydrides: Erosion, Release, and Toxicity Studies

• Published in: Biomacromolecules 2014-07, Vol.15 (7), p.2573-2582
• Main Authors: Poetz, Katie L, Mohammed, Halimatu S, Snyder, Brittany L, Liddil, Garrett, Samways, Damien S. K, Shipp, Devon A
• Format: Article
• Language: English
• Subjects: Applied sciences; Biocompatible Materials - chemistry; Cell Survival - drug effects; Cells, Cultured; Drug Carriers - chemistry; Exact sciences and technology; Humans; Hydrolysis; Kinetics; Photochemical Processes; Physicochemistry of polymers; Polyanhydrides - chemical synthesis; Polyanhydrides - toxicity; Polymerization; Polymers and radiations; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - toxicity
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm500420q

Several critical aspects of cross-linked polyanhydrides made using thiol–ene polymerization are reported, in particular the erosion, release, and solution properties, along with their cytotoxicity toward fibroblast cells. The monomers used to synthesize these polyanhydrides were 4-pentenoic anhydride and pentaerythritol tetrakis(3-mercaptopropionate). Techniques used to evaluate the erosion mechanism indicate a complex situation in which several phenomena, such as hydrolysis rates, local pH, water diffusion, and solubility, may be influencing the erosion process. The mass loss profile, the release rate of a hydrophilic dye, the rate of hydrolysis of the polyanhydride, the hydrolysis product solubility as a function of pH, average pK a and its cytotoxicity toward fibroblast cells were all determined. The solubility of the degradation product is low at pH values less than 6–7, and the average pK a was determined to be ∼5.3. The cytotoxicity of the polymer and the degradation product was found to be low, with cell viabilities of >97% for the various samples studied at concentrations of ∼1000–1500 ppm. These important parameters help determine the potential of the thiol–ene polyanhydrides in various biomedical applications. These polyanhydrides can be used as a delivery vehicle, and although the release profile qualitatively followed the mass loss profile for a hydrophilic dye, the release rate appears to be by both diffusion and mass loss mechanisms.