主链含膦酸酯的聚酸酐药物控制释放材料研究

通过二氯膦甲（乙）酸乙酯与对羟乙氧基苯甲酸反应，制备了二羧苯氧乙氧基膦甲（乙）酸乙酯，并其转化成混合醋酐并通过熔融缩聚，合成了主链含膦甲（乙）酸乙酯的聚酸酐，以二羧苯氧乙氧基膦甲（乙）酸乙酯，分别与１，３－双（４－羧基苯氧基）丙烷（ＣＰＰ）及癸二酸（ＳＡ）共聚，得到相应的共聚酸酐，对所合成的单体和聚合物的结构进行了表征，研究了它们的体外降解，酶促降解及其对抗肿瘤药物５－氟尿嘧啶和氨甲喋蛉的释放性能     

新型生物可降解医用高分子材料—聚酸酐

综述了新型生物的可降解医用高分子材料－聚酸酐的发展概况，包括聚酸酐的发展历史，分类，合成及应用，提出了今后的研究方向。     

含磷聚酸酐药物控制释放材料的研究

将二氯磷酸乙酯或苯酯与对羟乙氧基苯甲酸反应，制备了含磷酸酯键的二羧酸，将其转化为混合酸酐并通过熔融缩聚，合成了主链含磷酸酯键的聚酯酐，以含磷酸酯键二羧酸与１，３－双（４－羧基苯氧基）丙烷（ＣＰＰ）熔融共聚，得到一链到酯键的共聚酸酐研究了两类聚酸酐的体外降解，酶促降解，这些聚酸酐的降解过程包含酸酐键的断裂，也包含磷酸酯键断裂，前者比后者更容易断裂，核糖核酸酶和碱性磷酸酶能加速这类聚酸酐的降解，还研究     

EFFECT OF SUBSTITUTION POSITION OF HYDROXY GROUP AT BENZOIC ACID ON THE LUMINESCENT AND DEGRADATION PROPERTIES OF POLY[DI（CARBOXYPHENYL） SUCCINATE-co-SEBACIC ANHYDRIDE]S

In this work, two new diacids, di（m-carboxyphenyl） succinate （m-dCPS） and di（o-carboxyphenyl） succinate （o- dCPS）, were synthesized by reaction of m-, o-hydroxy benzoic acid with succinic chloride, respectively. Their corresponding copolymers with sebacic acid （SA）, P（m-dCPS：SA） and P（o-dCPS：SA）, were prepared by melt copolycondensation and characterized by NMR, UV and DSC methods. Compared with inherently fluorescent poly[di（p-carboxyphenyl） succinate- co-sebacic anhydride] （P（p-dCPS：SA））, P（m-dCPS：SA） and P（o-dCPS：SA） displayed different luminescent properties. P（m- dCPS：SA） could emit fluorescence under the excitation of both visible and UV light, while P（o-dCPS：SA） could only emit fluorescence when excited with UV light. Degradation rate of the two new copolyanhydrides increased with the increase of SA fraction in the copolymers. In addition, P（o-dCPS：SA） degraded more rapidly than P（m-dCPS：SA） with the same composition. Typical surface-degradation characteristics of these copolyanhydrides were observed.     

Polyanhydride modified unsaturated polyesters as injectable drug carriers: Synthesis and antitumor efficacy in Sarcoma-180 mice bearing tumor

New polyanhydride modified unsaturated polyesters, poly(dodecanedioic acid-tetradecanedioic acid) [P(DDDA-TA)] modified poly(fumaric acid-glycol) [P(FA-GLY)] copolymers, were prepared by melt polycondensation with corresponding polyanhydride and unsaturated polyester synthesized beforehand. The polyanhydride was characterized by FT-IR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), the liquid poly(fumaric acid-glycol) [P(FA-GLY)] and polyanhydride modified unsaturated polyesters were characterized by FT-IR, gel permeation chromatography (GPC) and viscosity of the polymers was measured with a Ubbelohde viscometer. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 °C and have properly drug release rate as drug carriers. The biocompatibility of P(DDDA-TA)-P(FA-GLY) copolymers under mice skin was also evaluated; macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DDDA-TA) [molar ratio M_DDDA:M_TA = 1.0:1.0, 20% weight ratio in polyanhydride modified unsaturated polyester]-P(FA-GLY) [molar ratio M_FA:M_GLY = 1.0:1.1] containing 5% adriamycin hydrochloride (ADM) in Sarcoma-180 mice bearing tumor exhibited increased volume doubling time (VDT) (21 ± 1.5 days) compared to plain subcutaneous injection of adriamycin hydrochloride (ADM) (7 ± 1.0 days), and the antitumor efficacy of injected preparation of P(DDDA-TA)-P(FA-GLY)-ADM inside tumor twice intervene 16 days exhibited an especially increased cytotoxic effect as revealed by increased volume doubling time (VDT) (32 ± 2.5 days). The studies suggested that P(DDDA-TA)-P(FA-GLY) copolymers as an effective and injectable carrier of antineoplastic drug like adriamycin hydrochloride have a very good foreground in treatment of noumenon tumor.     

Stimulation of trigeminal motoneurons by in vivo implantation of glutamate-impregnated microspheres

The objective of this study was to alter biomechanical forces generated by the muscles of mastication that affect the growth of the craniofacial skeleton through the implantation of neurotransmitter microspheres to stimulate trigeminal motoneurons (TMNe) in vivo. Polyanhydride microspheres containing L-glutamate were stereotaxically implanted 170–920 μm rostral to the left-side trigeminal motor nucleus (TMNu) in 17 Sprague–Dawley rats at 33–38 days old. Seven rats received blank-microsphere implants and two rats had empty delivery system penetration as controls. All rats were killed 10–14 days postsurgical for dissection, brain histology, osteometric data, and SEM analyses. Dimensions of the facial skeletons of glutamate-microsphere rats showed significant (P<0.01, P<0.05) differences when compared to control animals. Glutamate-microsphere animals also demonstrated significant (P<0.01) differences between the dimensions of their implant-and nonimplant-side facial skeletons. SEM analyses indicated that glutamate-microsphere rats had greater implant-side wear of their mandibular incisors compared to blank-microsphere or delivery system controls. The skeletal alterations in the glutamate-microsphere rats are hypothesized to be due to increased implant-side TMNe and masticatory muscle activity patterns.     

Ring opening polymerization of adipic anhydride initiated by dibutylmagnesium initiator

The ring opening polymerization of adipic anhydride (AA) initiated by dibutylmagnesium has been investigated in solution and in bulk. The results indicate that dibutylmagnesium is quite effective for the ring opening polymerization of AA. The polymer has been characterized by ¹H-NMR, IR and DSC. The end group analysis suggests that the AA polymerization might proceed through the “coordination-insertion” mechanism based on the acyl-oxygen cleavage of the AA ring.     

Storage Stability Study of Salicylate-based Poly(anhydride-esters)

Storage stability was evaluated on a biodegradable salicylate-based poly(anhydride-ester) to elucidate the effects of storage conditions over time. The hydrolytically labile polymer samples were stored in powdered form at five relevant storage temperatures (−12 °C, 4 °C, 27 °C, 37 °C, 50 °C) and monitored over four weeks for changes in color, glass transition temperature, molecular weight, and extent of hydrolysis. Samples stored at lower temperatures remained relatively constant with respect to bond hydrolysis and molecular weight. Whereas, samples stored at higher temperatures displayed significant hydrolysis. For hydrolytically degradable polymers, such as these poly(anhydride-esters), samples are best stored at low temperatures under an inert atmosphere.     

Stability of a salicylate-based poly(anhydride-ester) to electron beam and gamma radiation

The effect of electron beam and gamma radiation on the physicochemical properties of a salicylate-based poly(anhydride-ester) was studied by exposing polymers to 0 (control), 25 and 50 kGy. After radiation exposure, salicylic acid release in vitro was monitored to assess any changes in drug release profiles. Molecular weight, glass transition temperature and decomposition temperature were evaluated for polymer chain scission and/or crosslinking as well as changes in thermal properties. Proton nuclear magnetic resonance and infrared spectroscopies were also used to determine polymer degradation and/or chain scission. In vitro cell studies were performed to identify cytocompatibility following radiation exposure. These studies demonstrate that the physicochemical properties of the polymer are not substantially affected by exposure to electron beam and gamma radiation.     

Sustained release of acetylcholine in rat hippocampus using a polyanhydride drug-delivery system

A biodegradable polymer drug-delivery system has been developed for the selective localized application of agents to brain parenchyma. The copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP–SA) was impregnated with [³H]-acetylcholine (ACh) to form 1–5 μm microspheres. Drug-loaded microspheres were implanted into hippocampus bilaterally in 25 rats, and brain sections processed for autoradiography in groups of five animals at 2, 5, 10, 20 and 40 days, respectively. By densitometric analysis, the concentration of radiolabelled ACh in polymer and adjacent hippocampus rapidly decreased between 2 and 5 days, after which a gradual decrease in [³H]-ACh was observed up to 40 days. Between 2 and 40 days the concentration of radiolabelled ACh was reduced by 25.8% in polymer matrix and 40.1% in hippocampus. The spread of [³H]-label into adjacent brain parenchyma showed a similar temporal relationship, with initially wider dispersion at 2 days (44±3 μm), then a linear decrease in dispersion over the remaining period (10±0.9 μxm at 40 days), suggesting bulk flow of the radiolabel into hippocampus. Brain parenchyma showed only a minimal inflammatory reaction to the polyanhydride implants over all time periods. Polyanhydrides can provide localized continuous release of ACh to brain parenchyma, and may potentially be used to deliver various agents to brain in a number of clinical and experimental applications.