Studies On Preparation And Their Drug Release Behaviors Of Biodegradable Polymer Colloid Particles By Surface Polymerization

The preparation of microcapsules/microspheres of polylactide and polysaccharide by surface polymerization and the drug release behavior of these carriers were studied. First, polysaccharide and polylactide macromolecules containing vinyl group were synthesized. By the polymerization of the macromonomers enriching on the surfaces of ibuprofen (Ib) particles or solvent droplets, polysaccharide, polylactide and their composite capsules were prepared and the properties were evaluated. Taking Ib as a model drug, the drug release behaviors of the capsules were studied. The effects of the preparation parameters on the particle size and the thickness of the capsule wall were also investigated.By a coprecipitation method, the ibuprofen-loaded DEAE dextran (Ddex) nanospheres were prepared and the formation mechanism was suggested. The nanospheres were stabilized by adsorption of the Ddex onto the precipitated Ib particles, which were formed in situ because of the reduced solubility at low pH. With the increase of pH of the solution and the Ddex/Ib weight ratio, particle size of the resultant nanospheres decreased while the drug release rate increased.Using water-soluble carbodiimide as a condensation agent, methacrylic acid (MAA) was covalently grafted on the Ddex to obtaining polymerizable metharylated Ddex (MADdex). By coprecipitation-surface polymerization method, Ib nanoparticles coved by crosslinked MADdex were prepared with excellent stability. The loaded Ib could be released in a sustained manner. Hollow polysaccharide capsules were obtained after drug release.Polysaccharide nanocapsules were prepared by polymerization of methacrylated Ddex (MADdex) in the oil/water interface. The formation mechanism was discussed. The capsules had excellent stability with a nano-scale size and narrow size distribution. The loaded Ib could be sustainedly released from the capsules.Vinyl-terminated PLA macromonomer (PLAM) were synthesized by ring open polymerization of lactide (LC) catalyzed by stannous chloride in the presence of allyloxylethanol (AOE) as initiators. With the different weight ratio of LC/AOE, PLAM with various molecular weight was produced. Submicron-sized polylactide (PLA) capsules were obtained by the radical polymerization of PLAM, divinylbenzene (DVB) and MAA in the interface between water and oil phases. The formation mechanism was suggested as following. Firstly a layer of crosslinked PLAM copolymers is formed on the surface of a CHCl₃ droplet, then the unreactedPLAM precipitates onto the layer to form the capsule wall with the evaporation of the solvent, and finally the capsule is produced after the CHCI3 is volatilized completely. The hollow nature and the mechanism of the capsules were confirmed by various characterizations, e.g. TEM, CLSM SEM, AFM and IR.The polylactide capsules possessed good storage stability and ability of resisting pH and salt concentration. With the decrease of divinylbenzene concentration, the degradation of the capsules was accelerated. The pH of leaching solution and the MAA content in the surfaces of the capsule had effects on the degradation of the capsules. Dissolved Ib in the CHCI3, the drugs were incorporated into the PLA capsules. In vitro drug release showed that the release rate and final release amount of Ib decreased with the increase of molecular weight and the content of PLAM as well as DVB concentration. The initial burst release was reduced using PLAM with a higher molecular weight or content.By the copolymerization of MADdex and PLAM, composite nanocapsules were obtained composing of crosslinked MADdex-PLAM copolymer and unreacted PLAM. The capsules had excellent storage stability and ability of resisting pH and salt concentration. The drug release behavior showed that the MADdex-PLAM capsules had a better release property in a sustained manner than that of MADdex.The characteristics of the above three systems are discussed and analyzed. According to the common characteristics, a physical structure model of the capsules is provided to study the effects of preparation parameter on the capsule size and wall thickness, mainly for the system of the polylactide capsules. With the increase of the PLAM concentration and the oil/water volume ratio in the feed, the capsule size and wall thickness increase. The hydrophilic monomer, MADdex, has also certain effects on the capsules. At a constant PLAM concentration and oil/water volume ratio, the wall thickness is increased linearly as a function of the capsule size. The MADdex-PLAM capsules possess better composite properties than other carriers.