| The ?-alkyl cyanoacrylate have been used as tissue adhesives for the closure of skin wounds, as surgical glue, and as embolitic material for endovascular surgery. The a-alkyl cyanoacrylate polymers (PACA) were widely applied as various active drugs carrier materials because of the excellent biocompatibility and biodegradability. However, drug-loaded microspheres mentioned above are prepared by homopolymer of BCA or OCA,and drug release is difficult to control. Curcumin(Cur) is limited to use because of low solubility, although it has many good effects, such as anti-tumor, anti-inflammatory. In order to improve its bioavailability,curcumin was maken into liposomes, nanosized suspensions or loaded by polymers, but there are many problems. For example, low stability of liposomal, difficult surface modification of nanosized suspensions and organic solvent residue. In order to increase the degree of dissolution of curcumin,improve its wettability and bioavailability,hydrophilic-(3-cyclodextrin(HP-?-CD) was used to prepare curcumin inclusion(Cur-HP-?-CD). In this study, OCA and its copolymer microspheres with or without Cur-HP-P-CD are prepared by emulsification method. The main works in this paper are as follows:1. Preparation of OCA monomers.a-Octyl cyanoacrylate was synthesized by ester exchange reaction,condensation polymerization and depolymerization at high temperature. The structure and purity of products were characterized by IR, GC-MC, 1H-NMR and GPC. Purity of OCA monomer can reached above 98%.2. Preparation of poly(a-alkyl cyanoacrylate) microspheres without drug.POCA microspheres and poly(iBCA-co-OCA) copolymer microspheres were prepared by emulsification method using OCA or/and iBCA as monomers, poloxamer 188 as surfactant and water as medium. (1) Effects of concentration of poloxamer 188, pH, reaction time and the stirring speed on the size of microspheres and polydispersity (PDI) were investigated in detail.The optical condition of preparing POCA microspheres was: the amount of OCA was 0.08%, amount of poloxamer 188 0.08%, pH 2.0, stirring speed 750 rpm and reaction time 6 h. The particle size of POCA was 178 nm and PDI 0.048. (2) Effects of mass ratio of OCA and iBCA and its concentration on poly(iBCA-co-OCA) copolymer microspheres were studied. Results showed that hydrophobicity of the copolymer microspheres increased, particle size and molecular weight increased while Tg decreased, degradation prolonged,with increasing mass fraction of OCA.3. Preparation of drug-loaded microspheres of poly(a-alkyl cyanoacrylate)homopolymer.Cur-HP-(3-CD/PiBCA and Cur-HP-?-CD/POCA homopolymer microspheres were prepared by emulsification method using Cur-HP-?-CD as drug, OCA or iBCA as monomer. Effects of surfactant and drug concentration on particle size of microspheres, drug loading (DL) and entrapment efficiency(EE) were investigated. When the amount of monomer was 0.08%,concentration of poloxamer 188 0.05%, amount of Cur-HP-?-CD 0.07%, pH 2,stirring speed 750 rpm and reaction time 6 h, Cur-HP-?-CD/PiBCA drug-loaded microspheres with particle size 105nm, PDI 0.130, drug loading 9.96%, encapsulation efficiency 59.4% can be gotten. The morphology of microspheres was characterized by TEM. Also, Cur-HP-?-CD/POCA can be prepared with microspheres particle size 225 nm, PDI 0.036, drug loading 4.83%, encapsulation efficiency 28.6%.4. Preparation of drug-loaded microspheres of poly(a-alkyl cyanoacrylate)copolymer.Cur-HP-?-CD/poly(iBCA-co-OCA) copolymer microspheres were prepared by emulsification method using Cur-HP-?-CD as drug, OCA and iBCA as monomers. Effects of monomer mass ratio on drug loading and entrapment efficiency were investigated. Results showed that when content of OCA increased, drug loading and entrapment efficiency decreased, and the initial release of drug-loaded microspheres was accelerated. When the total concentration of monomer increased, the particle size of drug-loaded microspheres, encapsulation rate increased, but the cumulative release rate of drug decreased. |
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