Investigation of the cytotoxicity and insulin transport of acrylic-based copolymer protein delivery systems in contact with Caco-2 cultures.
Microparticles or nanospheres of hydrogels of crosslinked poly(methacrylic acid) grafted with poly(ethylene glycol) as well as crosslinked poly(acrylic acid) grafted with poly(ethylene glycol) were prepared for use as oral insulin delivery carriers. The copolymer carriers were synthesized by precipitation/dispersion polymerization that led to gel nanospheres or by bulk polymerization and subsequent size reduction of thin films to obtain gel microparticles. The cytotoxicity of these copolymers was investigated in contact with Caco-2 cell cultures using a metabolic assay to measure the effect of the presence of copolymers on the cell viability. The copolymers were found to exhibit no cytotoxic effect on the cell cultures. Insulin-loaded formulations were also tested for cytotoxicity and insulin transport studies across cell monolayers. The copolymers were shown to open the tight junctions between cells, increasing the available area for diffusion across the cell monolayer, and thus increasing the permeability of insulin across the monolayer.
Foss
Aaron C
AC
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712-0231, USA.
Peppas
Nicholas A
NA
D000179:Acrylates / Q000737:chemistry / Q000378:metabolism*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D000179:Acrylates; D007328:Insulin; D011506:Proteins; C036658:acrylic acid