Lemmouchi Y, Schacht E, Kageruka P, De Deken R, Diarra B, Diall O, Geerts S
Polymer Material Research Group, Institute for Biomedical Technologies, University of Gent, Belgium.
Biomaterials. 1998 Oct;19(20):1827-37. doi: 10.1016/s0142-9612(98)00074-x.
Copolymers of epsilon-caprolactone and L-lactide P(CL-LLA), epsilon-caprolactone and D,L-lactide P(CL-DLLA) and epsilon-caprolactone and trimethylene carbonate P(CL-TMC) were synthesized. The composition of comonomers and their sequence lengths were determined by means of 1H and 13C NMR measurements. The effect of the comonomer on the thermal properties was investigated by differential scanning calorimetry (DSC) analysis. The in vitro degradation of the rods obtained by melt extrusion of the synthesized copolymers and the commercial homopolymers poly(epsilon-caprolactone) P(CL) and poly(D,L-lactide) P(DLLA) was carried out in phosphate buffer (PB) pH 7.4 at 37 degrees C. The rate of degradation depends on comonomers and polymer composition. The in vitro release of the selected drugs, isometamidium chloride (IMM) and ethidium bromide (EtBr), from such devices was carried out under the same conditions as used for the in vitro degradation. The release experiments show that the release of IMM is faster than for EtBr. During the first stage, for IMM the release is governed by osmotic pressure whereas for EtBr the release is mainly diffusion-controlled. The in vitro release of these drugs is governed by polymer matrix degradation at the later stage of the release process. Comparative in vitro release study from the different polymers showed that the release depends mainly on the physical properties of the polymer. The in vivo experiments carried out in the field on cattle and in the laboratory on rabbits using the classical treatment (intramuscular injection) and the sustained release devices (SRD) subcutaneously implanted, showed that the prophylactic period is significantly enhanced in the case of SRD as compared to intramuscular injection. The comparative efficacy of SRD containing IMM and EtBr evaluated in the case of rabbits showed that, the SRD (IMM) prophylactic period is much longer than for SRD (EtBr).
合成了ε-己内酯与L-丙交酯的共聚物P(CL-LLA)、ε-己内酯与D,L-丙交酯的共聚物P(CL-DLLA)以及ε-己内酯与碳酸三亚甲基酯的共聚物P(CL-TMC)。通过1H和13C NMR测量确定了共聚单体的组成及其序列长度。采用差示扫描量热法(DSC)分析研究了共聚单体对热性能的影响。将合成的共聚物以及市售均聚物聚(ε-己内酯)P(CL)和聚(D,L-丙交酯)P(DLLA)通过熔融挤出得到棒材，在37℃、pH 7.4的磷酸盐缓冲液(PB)中进行体外降解。降解速率取决于共聚单体和聚合物组成。在与体外降解相同的条件下，对这类装置中所选药物氯化异美汀(IMM)和溴化乙锭(EtBr)进行体外释放研究。释放实验表明，IMM的释放速度比EtBr快。在第一阶段，IMM的释放受渗透压控制，而EtBr的释放主要受扩散控制。在释放过程的后期，这些药物的体外释放受聚合物基质降解的控制。对不同聚合物进行的体外释放比较研究表明，释放主要取决于聚合物的物理性质。在牛身上进行的田间体内实验以及在兔子身上进行的实验室体内实验，采用经典治疗方法(肌肉注射)和皮下植入缓释装置(SRD)，结果表明，与肌肉注射相比，SRD的预防期显著延长。在兔子身上评估含IMM和EtBr的SRD的比较疗效表明，SRD(IMM)的预防期比SRD(EtBr)长得多。
