| Starch microsphere(SM) is a kind of artificial derivant from natural starch. As drug delivery carrier, it has been used in the fields such as intranasal administration, arterial embolization, radiation therapy, immunoassay and so on. SM is one of the great potential new type drug delivery carrier. However, due to the complexity of the SM process and the diversity of the process parameters, one of the challenges in process is the preparation of the SM with narrow diameter distribution. SM also has shortcomings on the drug loading efficiency and drug control release. Moreover, SM is prepared by one-step cross-linked methods mostly and has single chemical properties, so it has single drug loading properties. In order to solve the above problems, this thesis studies the stabilitiy of inverse emulsion including starch granule. Based on these research, using soluble starch as raw material, epichlorohydrin (ECU) and N,N'-methylenebisacrylamide(MBAA) as crosslinker, this thesis studies the preparation of crosslingked starch microspheres(CSM) by the inverse emulsion method and the optimal conditions for preparation are studied. Using CSM as the raw material, the ionized starch microspheres are prepared.The morphologies and physical and chemical properties of the SM are characterized. The curcumin-loading CSM and arginine-loading CSM are prepared and their drug loading and drug release properies are observed separately. The main results are listed as follows:1. The stabilities of inverse emulsion including starch are investigated by the single factor test. The results show that when the value of HLB of emulsifier is 4.7, the concentration of the starch solution is 16%, volume ratio between oil phase and aqueous phase is 3:1, the agitation strength is 17500r/min mixing 30s, the amount of the emulsifier is 0.6%, inverse emulsion has the best stability.2.The optimum conditions of the starch microspheres crosslinked with ECH (ESM) preparation are determined by orthogonal experiments. The results show when the volume ratio between oil phase and aqueous phase is 4:1, the amount of crosslinker is 3 ml, the temperature is 45℃, the amount of emulsifier is 0.3%, the average diameter of ESM are smallest and when the volume ratio between oil phase and aqueous phase is 4:1, the amount of crosslinker is 4 ml, the temperature is 50℃, the amount of emulsifier is 0.4%, the deposition volume of ESM are smallest. Considered the two index, the optimum conditions of ESM preparation are decided as the volume ratio between oil phase and aqueous phase is 4:1, the amount of crosslinker is 3 ml, the temperature is 50℃, the amount of emulsifier is 0.4%. The average diameter of the ESM prepared under the condition is 39.5um, deposition volume is 1.1ml.3. The optimum conditions of the starch microspheres crosslinked with MBAA (ESM) preparation are determined by Uniform desgin experiments. The results show when the concentration of the initiator is 18mmol/L, the amount of the emulsifier is 0.23%, the concentration of the crosslinker is 0.025mol/L, the reaction time is 2.1h, the reaction temperature is 40.4℃, the volume ratio between oil phase and aqueous phase is 2:1, the speed of agitation is 400r/min, the average diameter of MSM is smallest and when the concentration of the initiator is 17mmol/L, the amount of the emulsifier is 0.23%, the concentration of the crosslinker is 0.025mol/L, the reaction time is 4.4h, the reaction temperature is 51.2℃, the volume ratio between oil phase and aqueous phase is 2.1, the speed of agitation is 400r/min, the deposition volume of MSM is smallest.4.The analysis results of SEM, IR and DSC prove that EMS is almost spherical, even distributing particulates with rough surface and has tri-dimensional structure, crosslink reaction occurs between some hydroxyl groups of starch. The analysis results of SEM, IR and DSC proved that MSM is spherical, diameter distribution of MSM is narrow, crosslink reaction between starch and MBAA is success, MBAA occurs polymerization during crosslink reaction. After crosslinked, the thermal stabilities of ESM and MSM are improved.5.With In-Vitro degradability model, the degradabilities of ESM and MSM are tested in simulated gastric fluid, simulated intestinal fluid and simulated blood. The results indicate that ESM and MSM have some degree anti-degradation ability in the artificial body fluids and the rate of the degradation is decreased with the diameter and the crosslinking degree increased. ESM and MSM have prospects on the application to colonic targeted drug delivery, arterial embolization and drug control release. 6. The stability of curcumin is studied and the result shows that it has good stability when pH value is 2-7. Lower temperature could improve the cucumin stability. The curcumin is soluble in the organic solvents and it has better stability in the 20% ethanol solution.7.Using the MSM as drug carrier, the curcumin-loading starch microspheres is prepared by adsorption method. The drug loading properties and drug release properties of curcumin-loading starch microspheres are studied. The results show the curcumin loading amount of MSM is increased with diameter decreased and with crosslinking degree increased. When the quantity ratio between MSM and curcumin is 5:1, the curcumin loading is 134.24mg/g, the rate of drug-loading is 83.9% after absorpting for 2h. The curcumin release ratio of the curcumin-loading MSM is 80.53% in the 20% ethanol solution including 0.8% sodium dodecyl sulfate after 25h. The analysis results of DSC prove that curcumin lose its crystal structure and exist as the complex with the MSM in curcumin-loading starch microspheres.8.Using the ESM as drug carrier, the arginine-loading starch microspheres is prepared by adsorption method. The drug loading properties and drug release properties of arginine-loading starch microspheres are studied. The results show the arginine loading amount of ESM is increased with diameter decreased and with crosslinking degree increased. When the quantity ratio between ESM and arginine is 2:1, the arginine loading is 31mg/g, the rate of drug-loading is 6.22% after absorpting for 1.5h. The arginine release ratio of the arginine-loading ESM is 85.53% in the water after 6h.9.Using the ESM as raw material and STP as ionize agent, the anionic starch microspheres is prepared. The analysis results of IR and DSC show that the crosslink reaction between STP and ESM is success and thermal stability of anionic starch microspheres increases. The drug loading properties and drug release properties of anionic starch microspheres are studied. The results show the arginine loading amount of anionic starch microspheres is higher than ESM, the arginine loading amount of anionic starch microspheres is increased with DS increased. When the quantity ratio between anionic starch microspheres and arginine is 250:1, the arginine loading of anionic starch microspheres with DS 0.02 is 4.54mg/g. The release of arginine from anionic starch microspheres has the phenomenon of drug burst release, but the anionic starch microspheres has better drug control release properties than ESM. 10.Using the MSM as raw material and GTA as ionize agent, the cationic starch microspheres is prepared. The analysis results of IR and DSC show that the reaction between GTA and MSM is success and cationic starch microspheres decomposes in a wider temperature range than MSM. The drug loading properties and drug release properties of cationic starch microspheres are studied. The results show the curcumin loading amount of cationic starch microspheres is higher than MSM, the curcumin loading amount of cationic starch microspheres is increased with DS increased. When the quantity ratio between cationic starch microspheres and curcumin is 250:1, the curcumin loading of anionic starch microspheres with DS 0.024 is 9.26mg/g. The release of curcumin from cationic starch microspheres has the phenomenon of drug burst release, but the cationic starch microspheres has better drug control release properties than MSM.
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