title: Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptides.
abstract: This work was focused on the investigation of temperature and pH-responsive polymeric composite membranes and their permeability to proteins and peptides in response to environmental stimuli. The composite membranes were prepared from nanoparticles of poly(N-isopropylacrylamide-co-methacrylic acid) of various NIPAAm:MAA ratios dispersed in a matrix of a hydrophobic polymer. N-Benzoyl-L-tyrosine ethyl ester HCl, momany peptide, Leuprolide, vitamin B(12), insulin, and lysozyme were used as model solutes. The morphology of the membranes was examined with SEM and permeation of the solutes was measured using side-by-side diffusion cells at varied temperatures and pH. Permeability of the solutes across the membranes increased with increasing temperature or particle concentration, while decreased with increasing pH and molecular size of the solutes. Membranes containing nanoparticles of more NIPAAm units exhibited higher thermal sensitivity, and those with higher MAA content showed more pH responsiveness, which was in line with the temperature and pH-responsive volume change of the nanoparticles. The change in permeability was quickly detected following the application of the stimuli. These results and partition study using vitamin B(12) supported the proposed gel-pore mechanism of solute permeation through these composite membranes.
authors.affiliation: Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ont., Canada M5S 2S2.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D016503:Drug Delivery Systems; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry; D016729:Leuprolide / Q000737:chemistry; D008566:Membranes; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D009113:Muramidase / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014805:Vitamin B 12 / Q000737:chemistry
chemical_list: D000178:Acrylamides; D005782:Gels; D007328:Insulin; D008567:Membranes, Artificial; D010455:Peptides; D011108:Polymers; D011109:Polymethacrylic Acids; D011506:Proteins; C085085:poly(N-isopropylacrylamide-co-methacrylic acid); D009113:Muramidase; D016729:Leuprolide; D014805:Vitamin B 12