title: In vitro evaluation of thiolated polydimethylaminoethylmethacrylate hydrogel sub-microparticles for oral insulin delivery.
abstract: In this investigation, novel cationic thiomer, Thiolated polydimethylaminoethylmethacrylate (PDCys) is synthesised and the feasibility of PDCys sub-microparticles as oral insulin delivery carriers is evaluated in vitro. The presence of both positive charge and thiol group in the same matrix plays a vital role in improving the paracellular permeability. Thiol groups interacts with cysteine rich subdomains via disulfide bond formation and positive charge interacts with sialic residues of mucus glycoproteins via electrostatic interaction, thereby increasing the mucoadhesivity. Cytotoxic evaluation by MTT assay shows that PDCys is nontoxic. Force and Work of adhesion of PDCys was found found to be higher than that of parent polymer. ELISA and Circular dichroism spectra confirms that PDCys retains the biological activity and conformation of insulin. Moreover, PDCys is capable of opening the tight junctions by actin and occludin filament dislocation. Furthermore, permeation of FD4 on Caco-2 cells is improved by 3.9 fold compared to the parent polymer. Preliminary studies suggest that thiolated particles can serve as potential vehicles for oral insulin delivery.
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695012, India.
authors.forename: T A
authors.initials: TA
authors.lastname: Sonia
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000268:Adhesiveness / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D007328:Insulin; D008689:Methacrylates; D011109:Polymethacrylic Acids; D013438:Sulfhydryl Compounds; C581648:thiolated polydimethylaminoethylmethacrylate; C038300:methylmethacrylate-methacrylic acid copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate