Synthesis, Characterization And Properties Study Of Novel Fluorescence Polyanhydrides

Polyanhydrides are one kind of biomaterial with characteristics of surface degradation and good biocompatibility. In the previous research, we found a series of aromatic polyanhydrides with fluorescence properties. Their structure is [OC(O)ArXC(O)(CH₂)₂C(O)] and Ar is benzene. When X is O, the polyanhydride is poly(p-carboxybenzene succinic mono ester anhydridee) (PCPS). When X is NH, the polyanhydride is poly(p-carboxy formamide benzonic anhydride). They can emit blue fluorescence irradiated by UV light and emit green irradiated by visual light.PCPS and PCEFB were unique polyanhydrides with fluorescence properties. But they have some shortcoming. For example, the PCEFB need row material as p-animo benzonic acid which have certain side-effect. The yield of CPS synthesis was too low and it was prepared difficultly in large-scale. So that, we applicated a new synthetic route with p-hydroxy benzonic acid and suncinic anhydride as start substance. Then a new polyanhydride, poly(bi-(p-carboxybenzene) succinic ester anhydride) (P(p-dCPS)) was obtained simply with similar structure as PCPS. Their copolyanhydride with SA, P(p-dCPS:SA) were synthesized to improve the solubility and adjust degradation rate. This series of copolyanhydrides can emit strong fluorescence when excited by UV and visual light.For evaluating the biocompatibility of this series of polyanhydrides, the male mouse were used as animal model and P(p-dCPS:SA) bars with three molar ration were implanted in the subcutaneous tissue. P(p-dCPS:SA) showed good biocompatibility. It have not provoked obvious inflammation and lesion abnormality..Microshperes made from fluoreacent polyanhydrides can be used as monitoring carriers in vivo. PCEFB and P(p-dCPS:SA) can not be prepared to microspheres directly. Microspheres made from PEFB/PLGA have been prepared and have good shapes. These micropheres owned phase seperation and PLGA existed in the surface. So that, we discarded mat method and use PEG to modified P(p-dCPS:SA). Then, a novel kind of amphiprotic block polymers were synthesized. Microspheres made from them wererouding and have good bioadhesive properties.For advanced research in the influence of the side-chain structure on the fluorescence properties, we prepared polyanhydrides similar to PCEFB with different acyloxy as sidechain. These polyanhydrides were poly(o-acetoxyl-p-carboxy formamide benzonic anhydride) (PACEFB), poly(o-carpoxyl-p-carboxy formamide benzonic anhydride) (PCCEFB), poly(o-Lauroxyl-p-carboxy formamide benzonic anhydride) (PLCEFB). The influence of different side-chain on the fluorescence were studied.With the same route of the preparation of (P(p-dCPS)), new cpolyanhydrides were synthesized. They were P(di-(m-carboxybenzene) succinic ester anhydrie)(P(m-dCPS)), P(di-(o-carboxybenzene) succinic ester anhydrie)(P(o-dCPS)),P(di-(3-methoxyl-4-carboxybenzene) succinic ester anhydrie)(P(dMOCPS)), (P(di-(3,5-dimethoxyl-4-carboxybenzene) succinic ester anhydrie)(P(ddMOCPS)). The influence of different mainchain on the fluorescence was studied as well as degradation properties in vitro.This thesis is composed of two part:The first part: New biodegradable, luminescent polyanhydrides: synthesis, characterization, properties and preparation of fluorescntmicrospheresA new luminescent copolyanhydrides, P(p-dCPS:SA) were synthesized by melt condensation from p-dCPS and SA. The copolyanhydrides were characterized by IR, NMR, UV-photometer, DSC and fluorophotometer. P(p-dCPS:SA) with different ration of SA can emit blue or green fluorescence when irradiated by UV or blue light. The max wavelength of emission was 410 nm when excited by 327 nm and it changes to 476, 510 nm when exposed to 462 nm. It was confirmed that the rate of degradation increased with SA content increasing in vitro. So that their degradation can be adjusted with controlling the content in copolyanhydrides. The copolyanhydrides have characterization of surface degradation, which was proved by SEM.For evaluating the biocompatibility of this series of polyanhydrides, the male mouse were used as animal model and P(p-dCPS:SA) bars with three molar ration were implanted in the subcutaneous tissue. In the 2, 6, 10, 15, 22, 30 days, the bars were get out. The subcutaneous tissue contact with the bars was get out and prepared to medical slices as well as liver and kidney. All the P(p-dCPS:SA) displayed good biocompatibility and have not provoked serious inflammation. No visible lesion of kidney and liver was observed. It can be observed that the fluorescence intensity of the polyanhydrides decreased with degradation procession, which supplied a new way for evaluation and characterization of polyanhydrides degradation in vivo.Amphiprotic block polymers, PEG-P(p-dCPS:SA)-PEG were synthesized and characterized by IR, ¹HNMR, GPC. The intensity of fluorescence decreased with P(p-dCPS:SA) decreased in copolymers when observed by fluorophotometer. Microspheres can be prepared successfully from tri-block copolymers with 30～50% PEG using simple o-w emusification. High content of PEG added the stability of emusification and lead to rouding microspheres. The copolyanhydrides have good bioadhesion as introduction of PEG and more PEG more bioadhesion effects.The second part: Fluorescent polyanhydrides with different structures:synthesis, characterization and propertiesPolyanhydrides similar to PCEFB with different acyloxy as side-chain were synthesized to study the influoence of sidechain structure on fluorescence. They were characterized by IR, ¹HNMR, UV-photometer, DSC, fluorophotometer. Introduction of side-chain added the flexbility of polymers and lead to decreaseing of Tg. Compared with PCEFB, the four polyanhydrides showed little difference in the UV sprctra and absorbance shifted to violet side from corresponding diacids. The difference in the length of side-chain has influence on their fluorescence properties. It can be concluded that the fluorescence of PCEFB excited by visual light was due to interaction of adjacent units on same main-chain. The fluorescence of PCEFB excited by UV light was of interaction of non-adjacent units on same main-chain.The kinds of copolyanhydrides with similar structure as P(p-dCPS:SA) were synthesized to study the influoence of mainchain structure on fluorescence, P(o-dCPS:SA), P(m-dCPS:SA), P(dMOCPS:SA), P(ddMOCPS:SA). They were characterized by IR, ¹HNMR, UV-photometer, DSC, fluorophotometer and the most attention was paid on their fluorescence properties. P(m-dCPS:SA), P(dMOCPS:SA), P(ddMOCPS:SA) have similar fluorescence properties as P(p-dCPS:SA) and can be exited by UV or visual light. But P(o-dCPS:SA) can be only excited by UV light. It can be concluded that fluorescence excited by visual light was due to interaction of units on the same main-chain. P(m-dCPS:SA) and P(o-CPS:SA) have better solubility than P(p-CPS:SA) and degraded more quickly. Compared to P(p-CPS:SA), introsuction of one methoxyl can add their solubility and two symmetrical methoxyl can not. The methoxyl can accelerate their rate of degradation. The four new polyanhydrides have characteristics of surface degradation that can be observed by SEM.