| Polyelectrolyte, a new developed drug delivery system, which has many advantages, such as simple and mild preparation procedure, biocompatibility and biodegradability, excellent responsive drug release properties, and the merits to keep the bioactivity of polypeptide and proteins etc., has attracted much attention in the field of drug controlled release. Our work includes three parts: 1. Citrate cross-linked chitosan systemCitrate, a new negative-charged ion with small molecule, was use to cross-linking with chitosan. The swelling behavior and drug release under different conditions (include cross-linking pH, cross-linking time, release media, and coating agents) were measured. And it was found that citrate/chitosan film has a good pH-sensitive swelling and drug release behavior. The concentration of citrate and its pH has a great effect on the swelling and drug controlled release properties, high concentration and low pH of citrate solution, to some extent, lead to low swelling ratio and good drug release ability of citrate/chitosan film. When coated with sodium alginate, the drug release in SGF was greatly retarded, while that was not found when using peptide and heparin. The swelling ratio and drug release rate of citrate cross-linked chitosan in SGF was much more quick than that in SIF, so these film may be used as a drug carrier in the stomach.2. Ion cross-linked chitosan beads as a floating dosage form for the oral deliveryThe design of an oral controlled drug delivery system(DDS) should be primary aimed at achieving more predictable and increased bioavai lability of drugs. However, the development process is precluded by several physiological difficulties, such as an inability to restrain and localize the DOS within desired regions of the gastrointestinal(GO tract and the highly variable nature of gastric emptying process.Tr ipol yphosphate was usi'd as a cross-I inking agent in the preparationof chitosan beads. The effect of different circumstances, including cross-linking pH, cross-linking time, model drugs(ranitidine and salicylic acid) and drying method, to the drug controlled release of chitosan beads were estimated. And it was found that TPP cross-linked chitosan beads has no controlled effect on the release of ranitidine, however, it was contrary to salicylic acid, the maximum release time of it from TPP-chitosan beads reached 7 hours(for oven-dried only). In the meanwhile, although the total drug release time of freeze-dried beads was only 6 hours, the total drug release rate and the good floating ability of the freeze-dried beads in SGF decided that freeze-dried beads may have potential as a floating dosage form for oral drug delivery system.3. The preparation of N-alkyI chitosan and their drug release behaviorN-alkyl aldehyde was used in the preparation of N-alkyl chitosan. The relationship between reacting time and substitution degree was measured, and it was found that substitution degree increased quickly with the increasing of time within 2 hours, however, after 2 hours, the substitution degree (about 50%) almost did not change.N-ethyl chitosan, whose substitution degree are 24%, 38% and 49%, along with chitosan, were chosen to prepare salicylic acid loaded microspheres. SEM micrographs show that N-ethyl chitosan microspheres have a better scatter properties and a more spherical shape, and we believe that it was due to the introduction of alkyl, which greatly weakened the interaction of chitosan molecules. The salicylic acid release result shows that the drug release rate of N-ethyl chitosan microspheres was almost twice of that of chitosan microspheres, whereas their total drug release percent reached 80%, which was much better than that of chitosan microspheres, 40%. So the introduction of alkyl help reduce the drug loss.The drug release result also conveyed the message that the substitution of N-alkyl chitosan has little effect on their release behavior. The length of alkyl and their formation, in our point of view, mav be the main factor that has a g... |
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