疏水性聚胺类pH-敏感凝胶作为长效药物控释载体的研究

目的 考察疏水性聚胺类 pH 敏感凝胶作为长效药物控释载体的性能及影响因素。 方法 以 9 氨基吖啶 (9AA)为模型药物 ,用分光光度法测定不同疏水 /亲水组成的珠状凝胶在不同 pH的药物释放速度。 结果 甲基丙烯酸乙酯 (EMA)与甲基丙烯酸二乙氨基乙酯 (DEA)共聚得到的凝胶 ,在DEA含量仅为 10mol%时仍保持高度的pH 敏感溶胀性质。该凝胶在 pH≥ 6时可完全不释放药物 ,在pH 5的柠檬酸缓冲溶液中的释药时间可持续 32 0d以上。结论 通过选择聚胺类凝胶中适当的疏水性单体及调节凝胶中疏水 /亲水成分的配比 ,有可能按不同释药周期的需要 ,制备用于 pH

载药对pH 敏感凝胶溶胀和释药行为的影响

目的：研究载药对苯乙烯（Ｓｔ） —甲基丙烯酸二乙氨基乙酯（ＤＥＡ） 共聚物凝胶的溶胀和释药行为的影响。方法：以弱碱性的９氨基吖啶（９ＡＡ）或弱酸性的荧光黄（ＦＬ） 为模型药物，用显微镜观察法测定载药和未载药凝胶的溶胀比，用分光光度法测定载药凝胶的药物释放量。结果：即使９ＡＡ 和ＦＬ 的水溶性很小，载有９ＡＡ的凝胶在溶胀介质的ｐＨ 接近凝胶的相转变ｐＨ 时，溶胀速度大大提高，从而对凝胶的释药行为产生重要的影响。载有ＦＬ的凝胶溶胀速度大大降低，释药行为变得更为复杂。结论：水溶性很小的可离子化药物载入疏水性ｐＨ敏感凝胶后，同样对凝胶的溶胀和释药行为有重要影响，凝胶的释药行为受载药后凝胶的溶胀所控制。

Characterization of pH-sensitive Poly (acrylic acid-co-N-vinyl-2-pyrrolidone) Hydrogels Prepared by Gamma Radiation

The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electron microscope. The influence of absorbed dose, monomer composition and concentration on the swelling ratio (SR) of the hydrogels were investigated in detail. The effect of pH and temperature of the swelling medium on the swelling behavior of the hydrogels were also examined. The results show that the SR of the copolymer hydrogels decreases with the monomer concentration and absorbed dose increasing. The copolymer hydrogels show a better pH-sensitive behavior. In alkaline solution, the SR of the hydrogels is much higher than in acid solution.

Synthesis and characteristics of pH-and temperature-sensitive hydrogels of poly （DMAEMA/NIPAAm）

A kind of novel copolymer hydrogel of poly（N, N-dimethylaminoethyl methacrylate-co-N-isopropylacrylamide） （poly[DMAEMA/NIPAAm]） was synthesized by the initiation of K2S2O8, N, N＇-methylene-bis（acrylamide） （Bis） was used as the crosslinker. The effects of monomer content, pH and temperature on swelling ratio of the hydrogel were investigated; the thermo-sensitivity in deionized water and in physiological saline was determined. It showed that the swelling ratio of the hydrogel could be changed by changing the temperature or pH alternately. Both swelling ratio and LCST （Lower Critical Solution Temperature） of the hydrogel decreased with the increase of NIPAAm in the co-polymer content.

Synthesis and Characterization of Poly(N-Vinyl-2-Pyrrolidone/Itaconic Acid) Hydrogel

With N-vinyl-2-pyrrolidone (NVP) and itaconic acid(IA), poly(N-vinyl-2-pyrrolidone/itaconic acid)[P(NVP/IA)] hydrogel was synthesized by free radical solution polymerization. The structure of this (P(NVP/IA)) was characterized by IR. Effects of concentration of itaconic acid, amount of cross-link agent, N,N′-methylene-bis-acrylamide, reaction temperature, and time on properties of swelling ratio(SR) of the hydrogel were investigated.The results show that the best swelling property of the hydrogel is obtained at 50 ℃ and 1.5 h. pH sensitivity increases as the concentration of itaconic acid in the hydrogel system increases. Swelling ratio of the hydrogel decreases as the amount of cross-link agent increases.

Synthesis of poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine) and preparation of its hydrogel solution containing doxorubicin

Many pH-and temperature-responsive polymers have been designed for preparing hydrogel.In the present study,in order to decrease the pH sensitivity of reported poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine)(PAA1580-PEG4600-PAA1580),we designed and synthesized poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine)(PAA-PEG-PAA)with shorter length of PAA chain by decreasing reaction temperature for preparing PAA-PEG-PAA hydrogel solution containing doxorubicin(DOX).The PAA-PEG-PAA was synthesized via the Michael-addition polymerization.The characteristic of PAA-PEG-PAA was evaluated.The PAA-PEG-PAA hydrogel solution was prepared and investigated.DOX-loaded PAA-PEG-PAA hydrogel solution was prepared,and its in vitro DOX release and in vitro anti-tumor activity were evaluated.Our results indicated that the viscosity of PAA-PEG-PAA hydrogel solution was concentration-and temperature-dependent.The sol-gel transition temperature of PAA-PEG-PAA hydrogel solution(12%,w/w)ranged from 35 to 29℃,and its pH ranged from 6.0 to 7.4.The released DOX from DOX-loaded PAA-PEG-PAA hydrogel showed sustained release characteristics.The in vitro anti-tumor activity of DOX-loaded PAA-PEG-PAA hydrogel was confirmed in B16 F10 cell line.Considering the acidic tumor microenvironment,this DOX-loaded PAA-PEG-PAA hydrogel solution would be easy in situ administration for intra-tumor injection or para-tumor injection forming hydrogel at body temperature.We suggested that this DOX-loaded PAA-PEG-PAAhydrogel solution,if containing photothermal conversion agents,would have a potential further use for photothermal therapy.