Shikanov Ariella, Domb Abraham J
Department of Medicinal Chemistry and Natural Products, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Biomacromolecules. 2006 Jan;7(1):288-96. doi: 10.1021/bm050648+.
The investigated polymers, poly(sebacic acid-co-ricinoleic acid) containing > or =70% ricinoleic acid, may be injected via a 22 gauge needle and become gel upon contact with aqueous medium, both in vitro and in vivo. Various properties of the polymers including viscosity, thermal analysis, and in vivo behavior, before and after exposure to aqueous medium, were determined. These polymers were observed using scanning electron microscopy (SEM) at dry and wet states. It was found that the viscosity and melting temperature of P(SA:RA) increased after exposure to buffer. The viscosity at 37 degrees C of P(SA:RA)3:7 had the highest increase: from 4200 cP before to 8940 cP after exposure to buffer; in the case of P(SA:RA)25:75 before exposure to buffer the viscosity was 1150 cP while after it raised to 3200 cP. The viscosity of P(SA:RA)2:8 also increased from 400 cP before exposure to buffer to 1000 cP after. On the other hand polymer without sebacic acid, (poly(ricinoleic acid)), did not show gelation properties. Thermal analysis also showed an increase in the melting point of the polymers exposed to the aqueous medium during the first 24 h of incubation. Images obtained by SEM showed formation of a three-dimensional network in polymers exposed to buffers. When injected into animals, P(SA:RA) forms a solid implant in the injection site already at 8 h postinjection.
所研究的聚合物,即蓖麻油酸含量≥70%的聚(癸二酸 - 蓖麻油酸),可通过22号针头注射,并在体外和体内与水性介质接触后形成凝胶。测定了聚合物在接触水性介质前后的各种性质,包括粘度、热分析和体内行为。使用扫描电子显微镜(SEM)观察了这些聚合物在干燥和湿润状态下的情况。发现P(SA:RA)在接触缓冲液后粘度和熔点增加。P(SA:RA)3:7在37℃时的粘度增加最多:接触缓冲液前为4200厘泊,接触后为8940厘泊;对于P(SA:RA)25:75,接触缓冲液前粘度为1150厘泊,接触后升至3200厘泊。P(SA:RA)2:8的粘度也从接触缓冲液前的400厘泊增加到接触后的1000厘泊。另一方面,不含癸二酸的聚合物(聚蓖麻油酸)没有显示出凝胶化性质。热分析还表明,在孵育的前24小时内,接触水性介质的聚合物熔点升高。通过SEM获得的图像显示,接触缓冲液的聚合物中形成了三维网络。当注射到动物体内时,P(SA:RA)在注射后8小时就在注射部位形成了固体植入物。