ABSTRACT
In vitro oxidative stability of two siloxane poly(urethane urea)s synthesized using 4,4'-methylenediphenyl diisocyanate (in SiPUU-1) and Isophorone diisocyanate (in SiPUU-2) linked soft segment was evaluated using 20% H2 O2 and 0.1 mol/L CoCl2 solution at 37°C under 150% strain. Commercially available siloxane polyurethane (Elast-Eon™ 2A) and polyether polyurethane (ChronoThane P™ 80A) were used as negative and positive controls, respectively. ChronoSil™ 80A was included as another commercially available polycarbonate polyurethane. Scanning electron microscopic (SEM) examinations, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and molecular weight reduction revealed the extensive degradation of ChronoThane P™ 80A after 90 days while SiPUU-1, SiPUU-2 and Elast-Eon™ 2A showed no noticeable surface degradation. ChronoSil™ 80A showed degradation in both soft and hard segments. Tensile testing was carried out only on unstrained polyurethanes for 90 days. ChronoThane P™ 80A showed 35% loss in ultimate tensile strength and it was only 13-14% for SiPUU-1 and Elast-Eon™ 2A. However, the tensile strength of ChronoSil™ 80A was not significantly affected. The results of this study proved that SiPUU-1 possess oxidative stability comparable with Elast-Eon™ 2A. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2557-2565, 2019.
Subject(s)
Biocompatible Materials/chemistry , Elastomers/chemistry , Materials Testing , Polyurethanes/chemistry , Siloxanes/chemistry , Tensile Strength , Oxidation-ReductionABSTRACT
Chain extension by diisocyanate condensation provides a versatile and convenient means for preparing block copolymers. We have utilized this chemistry to prepare reducible multiblock polycations for siRNA delivery. This approach, an alternative to oxidative coupling, was suitable for preparing multiblock polycations with defined molecular weight and architecture. The polymer, PEG-b-multi-(polyhexylurea-co-oligo-L-lysine)-b-PEG, was capable of electrostatically condensing siRNA to form nano-sized polyplexes across a broad compositional range. We demonstrated that the polyplexes enter the cells via endocytosis and interact with the endosome membrane leading to destabilization and hence endosome escape. Another feature of these polymers is their multiple intra-chain disulfide linkages. This enables weakening of the polyplex via chain scission within the cytosol's reductive environment. In addition to the controlled preparation of the polymer, the polyplexes were capable of delivering siRNA in vitro to silence greater than 50% green fluorescent protein expression with negligible toxicity.
Subject(s)
Absorbable Implants , Drug Implants/chemical synthesis , Nanocapsules/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Animals , CHO Cells , Cell Survival/drug effects , Cricetinae , Cricetulus , Crystallization/methods , Diffusion , Drug Implants/administration & dosage , Gene Silencing/physiology , Materials Testing , Nanocapsules/administration & dosage , Nanocapsules/ultrastructure , Particle SizeABSTRACT
This study assessed the long-term biological response of a perfluoropolyether-based polymer developed as a corneal inlay to correct refractive error. The polymer formulation met chemical and physical specifications and was non-cytotoxic when tested using standard in vitro techniques. It was cast into small microporous membranes that were implanted as inlays into corneas of rabbits (n = 5) and unsighted humans (n = 5 + 1 surgical control) which were monitored for up to 23 and 48 months respectively. Overall, the inlays were well tolerated during study period with the corneas remaining clear and holding a normal tear film and with no increased vascularisation or redness recorded. Inlays in three human corneas continued past 48 months without sequelae. Inlays in two human corneas were removed early due to small, focal erosions developing 5 and 24 months post-implantation. Polymer inlays maintained their integrity and corneal position for the study duration although the optical clarity of the inlays reduced slowly with time. Inlays induced corneal curvature changes in human subjects that showed stability with time and the refractive effect was reversed when the inlay was removed. Outcomes showed the potential of a perfluoropolyether inlay as a biologically acceptable corneal implant with which to provide stable correction of refractive error.
Subject(s)
Cornea/drug effects , Ethers/pharmacology , Fluorocarbons/pharmacology , Prostheses and Implants , Refractive Errors/therapy , Adult , Aged , Animals , Cornea/surgery , Disease Models, Animal , Female , Humans , Male , Middle Aged , Prosthesis Implantation , Rabbits , Time Factors , Young AdultABSTRACT
Several acrylic hydrogels were prepared via ultrasonic polymerization of water soluble monomers and macromonomers. Ultrasound was used to create initiating radicals in viscous aqueous monomer solutions using the additives glycerol, sorbitol or glucose in an open system at 37 degrees C. The water soluble additives were essential for the hydrogel production, glycerol being the most effective. Hydrogels were prepared from the monomers 2-hydroxyethyl methacrylate, poly(ethylene glycol) dimethacrylate, dextran methacrylate, acrylic acid/ethylene glycol dimethacrylate and acrylamide/bis-acrylamide. For example a 5% w/w solution of dextran methacrylate formed a hydrogel in 6.5min in a 70% w/w solution of glycerol in water at 37 degrees C with 20kHz ultrasound, 56Wcm(-2). The ultrasonic polymerization method described here has a wide range of applications such a biomaterial synthesis where initiators are not desired.
