低温辐射聚合制备聚合物药的慢释放研究

本文研究了低温辐射慢释放药的单体配比、药物含量及辐射刺量对药物释放速率的影响。结果表明,增加疏水性单体MMA,可以有效地控制大分子量药物消炎痛的释放速率;增加MMA及EDGMA,可以有效地控制小分子量药物5-Fu的释放速率;增加5-Fu的比例,可以降低5-Fu的释放速率;随辐照剂量的增加,聚合物药中5-Fu的释放量降低,二者之间成正比关系。     

含葡糖基酮洛芬乙烯醇酯共聚物的合成及其药物释放性能

分别利用化学法和酶促法合成了酮洛芬乙烯酯和葡萄糖丁二酸乙烯酯（6-O-乙烯丁二酰-D-葡萄糖）2种聚合单体,通过2种单体的自由基聚合反应制备了具有较高分子量的酮洛芬葡萄糖共聚物前药,通过IR、NMR对聚合物的结构进行了表征,用GPC方法测定共聚物分子量。 研究了聚合单体投料比例对共聚物分子量和载药量的影响。 结果表明,随着药物乙烯酯在投料中比例的增加,聚合物前药的分子量逐渐下降,聚合物中酮洛芬的载药量逐渐增加。 酮洛芬含糖聚合物前药的体外释放研究表明,酮洛芬的释放时间大大延长,达到了缓释的目的,释药速率随着聚合物前药中葡萄糖含量增加而加快。 聚合物前药的释放动力学模拟结果显示,共聚物释药更符合一级动力学释放模型。     

PLA大分子单体接枝NVP共聚物的合成与性能

制备了末端为双键的功能化聚乳酸大分子单体(PLA-HEMA),并以此大分子单体与N-乙烯基吡咯烷酮(NVP)进行自由基溶液共聚,合成了具有亲水性PVP-PHEMA主链和疏水性PLA支链的接枝共聚物。用FT-IR1、H-NMR、GPC、DSC、表面接触角测定研究了共聚物的结构与性能。结果表明:共聚物为非晶聚合物;NVP的摩尔投料量对共聚物的性能有显著影响,随NVP投料量增大,共聚物的分子量有所下降,玻璃化转变温度(Tg)增大;由于亲水性PVP和PHEMA链段的引入,共聚物的亲水性优于相应的线型聚乳酸材料。     

对二氧环己酮—乙交酯共聚物的合成及性能研究

本文研究了对二氧环己酮与乙交酯无规共聚物的化学结构，热性能。体外降解性能及共聚反应动力学。研究结果表明，随着单体配比中乙交酯含量的增加，共聚物中乙交酯含量增加，共聚物结晶能力下降，玻璃化转变温度升高，降解速率加快。随着聚合反应时间的延长，单体转化率及聚合物分子量不断增加。聚合时间超过96小时后，转化率及分子量变化趋于平缓。     

聚烯丙基氯化铵模板对AM/AA共聚物结构的影响

采用IR,1H-NMR和13C-NMR研究了聚烯丙基氯化铵(PAAC)模板对丙烯酰胺(AM)/丙烯酸(AA)共聚产物结构的影响,发现这种模板对共聚物P(AM/AA)序列结构和分子量有重要影响.由于共聚合体系中AA单体在PAAC模板聚合物上预组装,使得模板体系共聚物比无模板体系共聚物的AA和AM序列长度显著增加.这种类似多嵌段结构得到pKa′测定的进一步验证.另外模板分子量大小,模板和AA单体摩尔比,AM和AA摩尔比对共聚物结构的影响也进行了研究.应当指出这种模板聚合产物分离模板后仍有少量不能分离掉的PAAC聚合物存在.     

聚(碳酸酯-co-磷酸酯)的酶促合成及性能

以猪胰脂肪酶或假丝酵母皱褶酶为催化剂, 100℃下通过本体聚合成功地合成了三亚甲基碳酸酯(TMC)和2-乙氧基-2-氧-1,3-二氧磷杂环戊烷(EEP)的无规共聚物(poly(TMC-co-EEP)). 研究了酶浓度, 聚合反应时间以及共聚单体投料比等因素对共聚物分子量和产率的影响. 随着酶(PPL或CL)浓度的增加, 共聚物分子量降低. 同时, 随着EEP投料比的增加, 共聚物的分子量也降低. 共聚物数均分子量最大可达到10200. 随着共聚单体投料摩尔比(EEP/TMC)从0增加到5︰10, 共聚物的玻璃化温度从-28℃降低到-41.7℃. 体外降解实验表明: 共聚物中磷酸酯含量越高, 降解速率越快.     

聚己内酯－聚乙二醇嵌段共聚物Ⅱ．组成、结晶性同降解性间关系

采用ＤＣＳ法测定了新嵌段共聚物聚己内酯－聚乙二醇嵌段共聚物的结晶性，研究了共聚物的结晶性同组成及降解性的关系。结果表明随着共聚物中ＰＥＧ组分的含量和分子量增加，共聚物的结晶性下降，亲水性提高，降解速度加快。     

P(AA-co-PEGLA)凝胶对吡罗昔康的控释作用

将两亲性大单体聚氧乙烯月桂醇醚丙烯酸酯(PEGLA)与丙烯酸(AA)通过UV引发聚合,制备了水凝胶P(AA-CO-PEGLA).以水难溶性吡罗昔康为模型药物,研究了凝胶中PEGLA含量对栽药量的影响.结果表明;吡罗昔康的栽药量随着PEGLA含量的增加而提高,当凝胶中的PEGLA的摩尔分数(x)从0增加到60%时,载药量从1.24 mg/g提高到17.36 mg/g.吡罗昔康体外释放研究表明:P(AA-co-PEGLA)凝胶可保护药物不被胃酸等破坏,而在肠中释放.药物的释放速率随着凝胶中PEGLA含量的增加而降低,表现出明显的缓释作用.用Weibull方程拟合释放曲线,指数因子(b)0.88～0.97,表明对吡罗昔康释放的控制是扩散和高分子链松弛协同作用的结果.     

负载钛系催化剂催化合成高反式丁二烯-异戊二烯共聚物

采用负载钛系催化剂 [TiCl4 MgCl2 (i Bu) 3Al]催化丁二烯 (Bd) 异戊二烯 (Ip)共聚合 ,研究了单体配比、聚合温度、烷基铝浓度和催化剂浓度及单体浓度等对共聚合速率及共聚物特性粘数的影响 .结果表明 ,当单体配比中Bd (Bd +Ip)摩尔百分比≤ 2 0 % ,可制得高分子量的共聚物 .IR光谱分析及1 H NMR分析表明所得共聚物为高反式 1,4 结构 ,丁二烯单体单元的反式 1,4 含量大于 90 % ,异戊二烯单体单元的反式 1,4 含量大于 98% ,共聚物中丁二烯含量高于单体初始配比中的含量 .在一定的载钛量下 ,聚合条件对共聚物的微观结构影响不大     

环糊精聚合物功能化聚乳酸/聚乙烯基吡咯烷酮共聚物膜的制备与性能

合成了丙烯酸酯封端的PLA-PEG-PLA大分子单体(PELA-DA)与甲基丙烯酸缩水甘油酯(GMA)修饰的β-环糊精聚合物(CDP-g-GMA),不同配比的PELA-DA、CDP-g-GMA及N-乙烯基吡咯烷酮(VP)的DMF溶液经光引发自由基聚合制备了环糊精聚合物功能化聚乳酸/聚乙烯基吡咯烷酮共聚物膜.1H-NMR证实了PELA-DA及CDP-g-GMA大分子单体的成功合成.利用XRD、DTMA、TGA、吸水性及体外降解性等表征方法对合成的共聚物膜的结构与性能进行了表征.XRD测试表明,共聚物膜中PELA-DA及CDP-g-GMA组分的结晶性受到抑制与破坏;吸水性及体外降解测试显示,CDP-g-GMA的引入改善了共聚物膜的亲水性及水解降解性;DTMA及TGA测试结果表明,随着CDP-g-GMA引入量的增加,共聚物膜的储能模量(E')、玻璃化转变温度(Tg)及热稳定性增加.以甲基橙(MO)为水溶性模型药物,考察了共聚物膜对MO负载及释放模式,研究发现,CDP-g-GMA引入量的增加有利于提高MO的负载量,MO经过初期(12 h)爆释后,以一种缓慢的持续的方式进行释放.     

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.     

Morphology and temperature responsiveness–swelling relationship of poly(N‐isopropylamide–chitosan) copolymers and their application to drug release

Poly [N‐isopropylacrylamide (NIPAAm)–chitosan] crosslinked copolymer particles were synthesized by soapless emulsion copolymerization of NIPAAm and chitosan. An anionic initiator [ammonium persulfate (APS)] and a cationic initiator [2,2′‐azobis(2‐methylpropionamidine)dihydrochloride (AIBA)] were used to initiate the reaction of copolymerization. The chitosan–NIPAAm copolymer synthesized by using APS as the initiator showed a homogeneous morphology and exhibited the characteristic of a lower critical solution temperature (LCST). The copolymer synthesized by using AIBA as an initiator showed a core–shell morphology, and the characteristic of LCST was insignificant. The LCST of the chitosan–NIPAAm copolymer depended on the morphology of the copolymer particles. In addition, the chitosan–NIPAAm copolymer particles were processed to form copolymer disks. Then, the effect of various variables such as the chitosan/NIPAAm weight ratio, the concentration of crosslinking agent, and the pH values on the swelling ratio of chitosan–NIPAAm copolymer disks were investigated. Furthermore, caffeine was used as the model drug to study the characteristics of drug loading of the chitosan–NIPAAm copolymer disks. Variables such as the chitosan/NIPAAm weight ratio and the concentration of the crosslinking agent significantly influenced the behavior of caffeine loading. Two factors (pore size and swelling ratio) affected the behavior of caffeine release from the chitosan–NIPAAm copolymer disks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3029–3037, 2004     

In vitro release of protein from poly(butylcyanoacrylate) nanocapsules with an aqueous core

Factors influencing the in vitro release of bovine serum albumin (BSA) from poly(butylcyanoacrylate) (PBCA) nanocapsules, such as the pH value, BSA loading, the polymeric nanocapsule walls and protein molecular weight, were investigated in detail. The BSA release rate was affected by the degradation rate of the polymeric wall and protein loading. For low molecular weight proteins, the initial burst release was faster than that of high molecular weigh proteins and got to equilibrium quickly. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis results showed that BSA encapsulated within PBCA nanocapsules did not suffer covalent aggregation or fragmentation during the initial days of in vitro incubation. For nanocapsules prepared by interfacial polymerization in water-in-oil microemulsions, these findings were useful as a foundation for the development of nanocapsules with desired properties.     

INVESTIGATION OF POLYDL-LACTIDE-b-POLY（ETHYLENE GLYCOL）-b-POLYDL-LACTIDE MICROSPHERES CONTAINING PLASMID DNA

PolyDL-lactide (PDLLA) and the block copolymer, polyDL-lactide-b-poly(ethylene glycol)-b-polyDL-lactide (PELA) were used as the microsphere matrix to encapsulate plasmid DNA. The PDLLA, PELA, pBR322-1oaded PDLLA and pBR322-1oaded PELA microspheres were prepared by solvent extraction method based on the formation of multiple w1/o/w2 emulsion. The microspheres were characterized by surface morphology, mean particle size, particle size distribution and loading efficiency. The integrity of DNA molecules after being extracted from microspheres was determined by agarose gel electrophoresis. The result suggested that plasmid DNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could prevent plasmid DNA from being digested by DNase. The in vitro degradation and release profiles of plasmid DNA-loaded microspheres were measured in pH - 7.4 buffer solution at 37℃. The in vitro degradation profiles of the microspheres were evaluated by the deterioration in microspheres surface morphology, the molecular weight reduction of polymer, the mass loss of microspheres, the changes of pH values of degradation medium, and the changes of particle size. The in vitro release profiles of the microspheres were assessed by measurement of the amount of DNA presented in the release medium at determined intervals. The release profiles were correlation with the degradation profiles. The release of plasmid DNA from PELA microspheres showed a similar biphasic trend, that is, an initial burst release was followed by a slow, but sustained release.     

聚L-谷氨酸担载胰岛素口服微球的制备与评价

以聚L-谷氨酸为载体材料, 采用无水乳液法制备了口服胰岛素微球, 微球直径在5~20 μm, 载药质量分数为5%~9%. 载药微球具有良好的pH敏感释放行为, 在胃模拟液中2 h释放量约为5%, 在肠道模拟液中2 h释放90%以上. 考察聚合物分子量、溶液浓度、理论投药量及混合材料对微球释放行为的影响.     

Block Copolymer Capsules with Structure‐Dependent Release Behavior

Although high‐boiling non‐solvent induced macrophase separation in emulsion droplets has been widely applied for the fabrication of polymeric capsules, precise control of their structures remains a great challenge. Herein, block copolymer capsules with tunable shell structures were fabricated by employing a non‐solvent as a liquid template in emulsion droplets. The properties of the non‐solvents dictate the phase separation sequence in the droplets and the capsule formation mechanism. Two different pathways for capsule formation were observed, and could be applied to predict the shell structure. The structured capsules could be transformed into mesoporous capsules, which demonstrated an intriguing structure‐dependent release behavior. Capsules with spherical shell structures displayed the best permeability, while those with lamellar shell structures showed the slowest release, but with a stepwise profile. After loading with an anticancer drug, different capsules induced different apoptosis ratios in cancer cell studies.     

苯乙烯-马来酸酐共聚物的生物降解性研究

合成了一系列苯乙烯．马来酸酐共聚物(SMA)。并对共聚物的结构进行了表征。用土埋法和CO2释放法研究了共聚物的生物降解性。探讨了分子量、组成、环境等因素对生物降解性的影响,发现共聚物的分子量降低。降解率增大;共聚物中马来酸酐含量提高。降解率增大;适宜的环境有利于生物降解。     

Preparation of liquid crystal emulsion and its application performance study

The aim of this study was the formulation composition and characterization of the liquid crystal (LC) emulsion. First, influences of formulation composition on preparation of LC structure were studied, including the aliphatic alcohols with different carbon chain length, the liquid oils with different polarities, the sodium chloride, and the polygons. The results showed that fatty alcohols which is closer to the hydrophobic group of the emulsifier, little liquid oil, and little polyols were conducive to form LC structure. Then, the application performance of LC structure emulsion was studied. The results showed that compared with the conventional structure emulsion, the LC structure emulsion had more excellent moisturizing property, slow release effect, and the promoted penetration effect.     

含水核载牛血清白蛋白聚氰基丙烯酸丁酯微囊的制备及体外释放

利用界面乳液聚合方法制备了新型含水核载牛血清白蛋白 (BSA)的聚氰基丙烯酸丁酯 (PBCA)纳米微囊 .分别研究了纳米微囊的粒径及其分布 ,表面Zeta电势的变化 .并以牛血清白蛋白为模型药物考察了药物包裹率和载药量的变化以及载药纳米微囊在磷酸缓冲溶液中的体外释放行为 .结果表明 ,所制备的纳米微囊平均粒径为 2 0 0nm ,多分散度为 0 2 2 6;表面Zeta电势的变化证明了BSA是包裹于纳米微囊的内部而不是吸附在其表面 ;包裹率和载药量取决于水相中BSA的初始浓度 ,当BSA的浓度为 0 8mg mL时 ,包裹率和载药量分别为 3 5 %和 0 485× 1 0 - 9mol mg;药物的释放速率取决于纳米微囊的壁厚 ,通过调节壁厚可以达到控释的目的     

Investigation of a novel thermogelling hydrogel for a versatility of drugs delivery

The P(CL-PDO)-PEG-(P(CL-PDO)(PECP) copolymer hydrogel is an attractive thermogelling material for practical applications due to the fast dissolution of the copolymer in water and good stability of the resultant sol solution that is beneficial for guest matter mixing. In this paper, the degradation properties and drug release behavior of the hydrogel loaded with various types of drugs were evaluated. The integrity of the PECP hydrogel could preserve for 2?weeks and became viscous liquid after degradation time of 21?weeks. With the degradation time, both the molecular weight and weight loss of the hydrogel decreased gradually. NMR analysis of the degraded products indicated that the chain breaking of the copolymer mainly occurred within the sequence structures of PDO-PDO or PDO-PCL, implying the acceleration effect of PDO unit to the degradation of hydrogel. Three distinct types of drugs including small molecular hydrophobic, small molecular hydrophilic and hydrophilic macromolecular drugs were loaded into the PECP hydrogel to evaluate their release profiles. The result showed that the releasing periods for macromolecular protein or hydrophobic drug were extended to more than one month. Since these two types of drugs are loaded within different regions of the hydrogel due to their different hydrophobic/hydrophilic nature, the PECP hydrogel is expected to develop injectable system loaded with a versatility of drugs or guest matter for synergetic effect.