Surface Eroding, Semicrystalline Polyanhydrides via Thiol–Ene “Click” Photopolymerization

Surface eroding and semicrystalline polyanhydrides, with tunable erosion times and drug delivery pharmacokinetics largely dictated by erosion, are produced easily with thiol–ene “click” polymerization. This strategy yields both linear and cross-linked network polyanhydrides that are readily and fully cured within minutes using photoinitiation, can contain up to 60% crystallinity, and have tensile moduli up to 25 MPa for the compositions studied. Since they readily undergo hydrolysis and exhibit the oft-preferred surface erosion mechanism, they may be particularly useful in drug delivery applications. The polyanhydrides were degraded under pseudophysiological conditions and cylindrical samples (10 mm diameter × 5 mm height) were completely degraded within ∼10 days, with the mass-time profile being linear for much of this time after a ∼24 h induction period. Drug release studies, using lidocaine as a model, showed pharmacokinetics that displayed a muted burst release in the early stages of erosion, but then a delayed release profile that is closely correlated to the erosion kinetics. Furthermore, cytotoxicity studies of the linear and cross-linked semicrystalline polyanhydrides, and degradation products, against fibroblast cells indicate that the materials have good cytocompatibility. Overall, cells treated with up to 2500 mg/L of the semicrystalline polyanhydrides and degradation products show >90% human dermal fibroblast adult (HDFa) cell viability indicative of good cytocompatibility

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

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 p<i>K</i>_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 p<i>K</i>_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