Synthesis And Characterization Of Tubular Amphiphilic Networks With Controlled Pore Dimensions For Insulin Delivery
drug release; Polymer Science
A convenient laboratory process for the preparation of thin-walled (similar to 0.02 cm) tubular amphiphilic membranes has been developed. The membranes are suitable for implantation and isolation of pancreatic islets from immune responses. The process involves the simultaneous free radical copolymerization/crosslinking of dimethyl acrylamide (DMAAm) and methacrylate ditelechelic polyisobutylene (MA-PIB-MA) in narrow-bore (similar to 4 mm inner diameter) glass tubes horizontally rotating in a thermostated oven. The pore sizes of the membranes can be controlled by the length, i.e. molecular weight, of the hydrophilic poly(dimethyl acrylamide) (PDMAAm) segment (M-c,M-hydrophilic). Pore sizes, M-c,M-hydrophilic's, and molecular weight cut-off (MWCO) ranges of designed amphiphilic membranes were characterized in terms of Stokes (or viscosity) radii (Rs) and the relationships between these parameters were evaluated. Membranes were designed to allow the rapid diffusion of molecules such as insulin (M-n = 5733 g/mol, R-s = 1.34 nm) but to be opaque to serum albumin (M-n > 66 000 g/mol, R-s > 3.62 nm) and larger proteins such as immunoglobulins. The diffusion coefficients (D) and permeabilities (P) of tubular and flat-sheet amphiphilic membranes have been compared and were found to be similar. Membrane pore size dimensions of the tubular devices were determined by the out-diffusion of commercially available protein markers of known molecular weights (M-n = 6500-66 000 g/mol) and dimensions (R-s = 1.50-3.62 nm). It was found that the minimum M-c,M-hydrophilic or R-s that still allows the diffusion of insulin is similar to 800 g/mol or similar to 1.34 nm, respectively, and that the maximum M-c,M-hydrophilic or R-s that prevents the ingress of antibodies is similar to 5000 g/mol or similar to 3.62 nm, respectively. According to diffusion experiments, the presence or absence of lightly crosslinked 1% calcium alginate does not affect the rate of diffusion of glucose and insulin through our tubules. These membranes are being used in vivo for encapsulating islet cells for implantation to correct type 1 diabetes.
Kennedy J P; Fenyvesi G; Na S; Keszler B; Rosenthal K S
Designed Monomers and Polymers
2000
2000
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1163/156855500750198762" target="_blank" rel="noreferrer noopener">10.1163/156855500750198762</a>
Amphiphilic Gels With Controlled-mesh Dimensions For Insulin Delivery
Chemistry
Kennedy J P; Fenyvesi G; Na S; Keszler B; Rosenthal K S
Abstracts of Papers of the American Chemical Society
2000
2000-03
Journal Article or Conference Abstract Publication
n/a
Amphiphilic Gels With Controlled Mesh Dimensions For Insulin Delivery
drug release; islets; methacrylate)-1-polyisobutylene; networks; xenotransplantation
Kennedy J P; Fenyvesi G; Na S; Keszler B; Rosenthal K S
Polymer Gels: Fundamentals and Applications
2003
2003
Book Chapter
n/a
Amphiphilic Membranes With Controlled Mesh Dimensions For Insulin Delivery
immunosuppression; islets; networks; Polymer Science; porcine; release; xenotransplantation
A series of amphiphilic networks (membranes), consisting of hydrophilic poly(N,N-dimethylacrylamide) (PDMAAM) main chains crosslinked by hydrophobic telechelic polyisobutylene di- and trimethacrylates (MA-PIB-MA or circle divide (PEB-MA)(3)) have been synthesized and used for the preparation of thin-walled tubules suitable for the immunoisolation of porcine islets. The molecular weight cut-off (MWCO) ranges, insulin and glucose diffusion coefficients and permeabilities of various membranes have been determined. The molecular weight of the PDMAAM moiety between two hydrophobic crosslinking points M-c,M-hydrophilic) controls permeability, which in turn can be controlled by synthesis conditions. The strengths and elongations of water-swollen membranes crosslinked with circle divide (PIB-MA)(3) are superior by a factor of about two to those prepared with MA-PIB-MA. Based on the values from these experiments, a well-defined membrane prepared with circle divide (PEB-MA)(3) was selected and used to encapsulate porcine islet cells. Gratifyingly, the encapsulated islet cells remain functional and viable, and cells within the tubule release insulin upon glucose challenge. These in vitro experiments are sufficiently promising to encourage us to continue our studies to develop a bioartificial pancreas.
Kennedy J P; Fenyvesi G; Levy R P; Rosenthal K S
Macromolecular Symposia
2001
2001-06
Journal Article or Conference Abstract Publication
n/a