Drug Delivery and Drug Efficacy from Amorphous Poly(thioether anhydrides)

Abstract

The correlation between erosion and drug (lidocaine and 6‐mercaptopurine, 6‐MP) release from amorphous poly(thioether anhydrides), which are synthesized using radical‐mediated thiol‐ene polymerization, is reported. Cytotoxicity studies of the polymer toward human fibroblast human dermal fibroblasts adult, melanoma A‐375, and breast cancer MCF‐7 cells are conducted, and drug efficacy of a cancer and autoimmune disease drug (6‐MP) when released from the poly(thioether anhydrides) is examined against two cancerous cell types (A‐375 and MCF‐7). Erosion and drug release studies reveal that lidocaine release is governed by network erosion whereas 6‐MP is released by a combination of erosion and diffusion. The cytotoxicity studies show that all three cell types demonstrate high viability, thus cytocompatibility, to poly(thioether anhydrides). Toxicity to the material is dose dependent and comparable to other polyanhydride systems. The 6‐MP cancer drug is shown to remain bioactive after encapsulation in the poly(thioether anhydride) matrix and the polymer does not appear to modify the efficacy of the drug.

Dynamic covalent exchange in poly(thioether anhydrides)

“…35,36 Our group developed a new synthetic route for polyanhydrides based on radical-mediated thiol-ene polymerization, which occurs rapidly under mild reaction conditions. 37,38 In addition, to examine the erosion process and drug delivery potential of these materials, [39][40][41][42][43][44][45] we have also shown that we could successfully use these materials to make shape memory composites based on a low-melting poly-(ε-caprolactone)-based polyurethane electrospun fiber mat imbibed with the cross-linked polyanhydride. 46 We noted, however, that the ability of the composite to undergo shape memory was negatively impacted by the presence of anhydride exchange, and that a better understanding of dynamic exchange reaction is needed in order to produce polyanhydrides with optimized thermo-mechanical properties.…”

Polyanhydride Chemistry

“…The applicability of the amorphous poly(thioether anhydrides) is explored as drug-release carriers for the release of both hydrophilic and hydrophobic drugs such as 6-marcaptopurine and lidocaine in vitro conditions. 94 The release of the anticancer drug “6-marcaptopurine” from the polymer matrix is influenced by the diffusional behavior of the drug as well as the degradation process of the polymer. The release of aesthetic lidocaine is affected by polymer degradation rather than by diffusion.…”

Surface Eroding Methacrylic Anhydride Copolymers and Model Drug Release

“…[30] The application of the poly(thioether anhydrides) can be limited by the short degradation time span due to the high instability of the anhydride coupled with the low transition temperature (T g ) -induced segment mobility in these systems. [27][28][29][30][31] Poly(methacrylic anhydride) (PMAA) has similar properties to other crosslinked methacrylates, such as a high modulus and T g , and is also quite brittle. As is often the case with many polymeric materials, comonomers can be introduced to expand and tune the mechanical and thermal properties, along with erosion profiles, on an as-needed basis.…”

“…[ 28 ] We also evaluated drug release and efficacy in poly(thioether anhydrides) using lidocaine and 6‐mercaptopurine (6MP) a cancer/ autoimmune disease drug. [ 30,31 ] The viability of healthy cells HDFa was not impacted by 6MP at a polymer concentration of 1000 mg L −1 , however did show efficacy/bioactivity to cancerous cells A‐375 and MCF‐7 after encapsulation in the polymer matrix. [ 30 ] The application of the poly(thioether anhydrides) can be limited by the short degradation time span due to the high instability of the anhydride coupled with the low transition temperature ( T g ) ‐induced segment mobility in these systems.…”

“…[ 30 ] The application of the poly(thioether anhydrides) can be limited by the short degradation time span due to the high instability of the anhydride coupled with the low transition temperature ( T g ) ‐induced segment mobility in these systems. [ 27–31 ]…”