Preparation And Characterization Of Several Medical Polymer Composites In Supercritical Carbon Dioxide

Supercritical carbon dioxide (scCO₂) is nontoxic, nonflammable, cheap and easily available. It has been promoted as an ideal substitute for volatile organic solvents or additives. Besides the advantages of mild critical conditions and simple operation to access the critical state, scCO₂ has not only gas-like viscosity and diffusivity, but also liquid-like density and dissolving capacity. It is a perfect green solvent for polymerization reactions.With the fast development of medicine and material science, medical composite materials have aroused more and more attention. Biomedical materials of multi-sensitivities to environmental stimuli or anticoagulation capacity are two kinds of important medical materials. It is of great scientific significance and practical value to develop green synthesis methods and clean production processes for these kinds of medical composite materials and related drug delivery systems in scCO₂.To synthesize polymer/inorganic composite materials that combine the unique physical properties of inorganic particles with the favorable processability and flexibility of organic polymer matrix has been a novel approach to develop medical composite materials. Poly(N-isopropylacrylamide) (PNIPA) and related copolymers are valuable materials for temperature-responsive controlled drug delivery systems. Using scCO₂ as solvent, N-isopropylacrylamide (NIPA) as monomer and nano SiO₂ as inorganic reinforcer, Poly(N-isopropylacrylamide)/SiO₂ (PNIPA/SiO₂) composite materials were prepared through a two-step approach. The detailed process was as follows: nano SiO₂ particles were firstly surface modified by coupling agents to introduce unsaturated double bonds, and then underwent free radical polymerization with monomer NIPA in scCO₂ to produce polymer/inorganic composites. The characterization of the products showed that the combination of nano SiO₂ particles into the PNIPA matrix improved the swelling capacity and temperature sensitivity of the polymer microgels, and could help to improve the release effect of the thermoresponsive drug delivery systems derived from PNIPA.One-pot approach is another novel method to prepare polymer/inorganic composite materials. In scCO₂, SiO₂–poly(N-isopropylacrylamide) (SiO₂–PNIPA) composite particles derived from monomers NIPA, vinyltriethoxysilane (VTEO) and tetraethoxysilane (TEOS) were in situ prepared through the one-pot approach. During the synthesis procedure, the free radical polymerization of vinyl monomers and hydrolysis/condensation of siloxanes occurred simultaneously. TEM images of the obtained particles demonstrated that well-dispersed SiO₂–PNIPA particles with diameter less than 100 nm were formed. And the lower critical solution temperatures (LCSTs) of the composite microgels were higher than those of the PNIPA microgels. Ibuprofen (Ibu) was selected as a demonstrating medicine, and controlled drug delivery systems were prepared through an in situ polymerization-impregnated process. The in vitro release simulation of the Ibu-impregnated particles indicated that SiO₂–PNIPA composites could exhibit better drug releasing effect of the microgels as controlled drug delivery systems than the PNIPA microgels did.Thermoresponsive and magnetic poly(N-isopropylacrylamide)/Fe₃O₄ (PNIPA/Fe₃O₄) composite particles were successfully prepared with scCO₂ as reaction media. Fe₃O₄ microparticles were firstly synthesized by the titration- hydrolysis method. The characterization of the produced magnetic particles showed that they were ca. 100–200 nm in diameter. The PNIPA/Fe₃O₄ composite particles were derived from the free radical polymerization of monomer NIPA and nano Fe₃O₄ particles that had been surface modified by oleic acid (OA) or coupling agents to introduce unsaturated double bonds. The characterization of the composites verified that the polymer/inorganic particles possessed not only excellent temperature-sensitivity but also strong superparamagnetic characteristics. The saturation magnetization value of the dual-responsive composite particles reached 10.8 emu·g?1 and they could be expected as good candidates for magnetic targeted drug delivery systems in biomedicine.The conjugates of chitosan (CS) and L-arginine (Arg) have been verified as a kind of anticoagulants in biomedical materials. In scCO₂, the conjugates of chitosan and L-arginine (CS-Arg) were derived from the reaction of amino groups of the former and carboxyl groups of the latter under the catalysis of dehydrating agents. The experimental results indicated that the modification of chitosan by L-arginine could recach a fairly high substitute degree, and the catalysis effect of N,N'-dicyclohexyl carbodiimide (DCC) to prepare the CS-Arg conjugates in scCO₂ was better than that of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl).