title: Quantitative and qualitative toxicological evaluation of thiol-ene "click" chemistry-based polyanhydrides and their degradation products.
abstract: Quantitative and qualitative toxicological analyses of crosslinked, surface-eroding polyanhydrides (PAHs) made from thiol-ene "click" polymerizations are reported. The cytotoxicity of these PAHs was investigated against three skin-based cell types; melanoma (A-375), human dermal fibroblast adult (HDFa), and 3T3-J2 (mouse fibroblast) cells, thus providing insight into the potential for these PAHs to be used in dermal drug delivery applications. Apoptosis was evaluated quantitatively and qualitatively using MTT assay and fluorescence microscopic imaging as indication of cytotoxicity. Upon exposure of A-375 and HDFa cells to high concentrations (4000 mg/L) of crosslinked PAH, the respective morphologies remained relatively unchanged compared with nonexposed cells. The 3T3-J2 cell type was more sensitive towards the PAH, exhibiting minimal deformation of cell morphology at 4000 mg/L. The MTT assay and fluorescence imaging revealed that this PAH and its degradation products are highly cytocompatible at high concentrations and cytotoxicity observed is dosage/time dependent. Further, the PAH did not induce inhibition of tested cells' proliferation at high polymer concentration up to 2000 mg/L. The IC50 (concentration of the crosslinked PAH required to inhibit 50% cell viability) for HDFa and A-375 cells was determined to be 4300 ± 70 and 8500 ± 50 mg/L, respectively. The high cytocompatibility of this type of crosslinked PAH, in addition to their degradation products, towards these skin cells (standard and cancer cell types) suggests that the polymer may be viable for dermal-based drug delivery to normal and cancerous diseased tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1936-1945, 2016.
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York, 13699-5810.
authors.forename: Halimatu S
authors.initials: HS
authors.lastname: Mohammed
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York, 13699-5810.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Snyder
authors.affiliation: Department of Biology, Clarkson University, Potsdam, New York, 13699-5805.
authors.forename: Damien S K
authors.initials: DS
authors.lastname: Samways
authors.affiliation: Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York, 13699-5810.|Center for Advanced Materials Processing, Clarkson University, Potsdam, New York, 13699-5810.
authors.forename: Devon A
authors.initials: DA
authors.lastname: Shipp
mesh_terms: D016475:3T3 Cells; D000328:Adult; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D049388:Polyanhydrides / Q000737:chemistry / Q000633:toxicity*; D058105:Polymerization; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D018675:Toxicity Tests
chemical_list: D003432:Cross-Linking Reagents; D049388:Polyanhydrides; D013438:Sulfhydryl Compounds
keywords: cytotoxicity; polyanhydrides; surface erosion; thiol-ene “click” polymerization