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
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
Engineering Alkoxyphenacyl-Polycarbonate Nanoparticles for Potential Application in Near-Infrared Light-Modulated Drug Delivery via Photon Up-Conversion Process
800 nm; alkoxylphenacyl-based polycarbonates; biocompatibility; Chemistry; Doxorubicin; Drug Release; luminescence; Materials Science; mesoporous-silica; nanocrystals; Nanotechnology; Near-Infrared Light; photodynamic therapy; Physics; release; Science & Technology - Other Topics; Stimuli-Responsive; upconverting nanoparticles; uv
Photoresponsive delivery systems that are activated by high energy photo-triggers have been accorded much attention because of the capability to achieve reliable photoreactions at short irradiation times. However, the application of a high energy photo-trigger (UV light) is not clinically viable. Meanwhile, the process of photon-upconversion is an effective strategy to generate a high energy photo-trigger (in-situ) through exposure to clinically relevant near-infrared (NIR) light. In this regard, we synthesized photon upconverting nanocrystals (UCNCs) that were subsequently loaded into photoresponsive nanoparticles (NPs) that were prepared using alkoxyphenacyl-based polycarbonate homopolymer (UCNC-APP-NPs). UCNC loading affected resultant NP size, size distribution, colloidal stability but not the zeta potential. The efficiency of NIR-modulated drug delivery was impacted by the heterogenetic nature of the resultant UCNC-APP-NPs which was plausibly formed through a combination of UCNC entrapment within the polymeric NP matrix and nucleation of polymer coating on the surface of the UCNCs. The biocompatibility of UCNC-APP-NPs was demonstrated through cytotoxicity, macrophage activation, and red blood cell lysis assays. Studies in tumor-bearing (nu/nu) athymic mice showed a negligible distribution of UCNC-APP-NPs to reticuloendothelial tissues. Further, distribution of UCNC-APP-NPs to various tissues was in the order (highest to lowest): Lungs> Tumor > Kidneys > Liver > Spleen> Brain > Blood > Heart. In all, the work highlighted some important factors that may influence the effectiveness, reproducibility and biocompatibility of drug delivery systems that operate on the process of photon-upconversion.
Wehrung D; Chamsaz E A; Andrews J H; Joy A; Oyewumi M O
Journal of Nanoscience and Nanotechnology
2017
2017-07
Journal Article
<a href="http://doi.org/10.1166/jnn.2017.13449" target="_blank" rel="noreferrer noopener">10.1166/jnn.2017.13449</a>
Amphiphilic networks .10. Diffusion of glucose and insulin (and nondiffusion of albumin) through amphiphilic membranes
cells; Drug Release; Engineering; Materials Science; pancreas; sequential co-polymers; telechelic polymers; transfer agents inifers
Select semipermeable amphiphilic membranes have been prepared and their diffusional characteristics for glucose, insulin, and albumin investigated. The membranes were prepared by cast copolymerization of a hydrophilic monomer (i.e., N,N-dimethyl acrylamide, or N,N-dimethylaminoethyl methacrylate) with the hydrophobic crosslinker methacrylate-ditelechelic polyisobutylene. The products have sufficient mechanical properties for the fabrication of swollen membranes, sheets, tubes, etc. Membranes have been identified which allowed the rapid simultaneous countercurrent diffusion of glucose (M-n = 180 Da) and insulin (M-n = 5733 Da) but did not allow albumin (Mn similar to 60,000 Da) to pass. Evidently, the effective molecular weight cutoff point of these membranes is in the 6-60-KDa range. (C) 1997 John Wiley & Sons, Inc.
Shamlou S; Kennedy J P; Levy R P
Journal of Biomedical Materials Research
1997
1997-05
Journal Article
<a href="http://doi.org/10.1002/(sici)1097-4636(199705)35:2%3C157::aid-jbm3%3E3.0.co;2-m" target="_blank" rel="noreferrer noopener">10.1002/(sici)1097-4636(199705)35:2%3C157::aid-jbm3%3E3.0.co;2-m</a>