Leong K W, Brott B C, Langer R
Massachusetts Institute of Technology, Cambridge 02139.
J Biomed Mater Res. 1985 Oct;19(8):941-55. doi: 10.1002/jbm.820190806.
Polyanhydrides based on a variety of aromatic and aliphatic dicarboxylic acids were developed as bioerodible carrier matrices for controlled delivery applications. The high hydrolytic reactivity of the anhydride linkage provides an intrinsic advantage over other classes of bioerodible polymers in versatility and control of degradation rates. For example, using the poly[bis(p-carboxyphenoxy) alkane anhydrides] as models, polymers with degradation rates in the range of 10(-1) to 10(-4) mg/h/cm2 were obtained by changing the alkane from a methyl to a hexyl group. The polymers were characterized by infrared (IR), differential scanning calorimetry, gel permeation chromatography, and scanning electron microscopy (SEM). Near zero-order degradation kinetics were observed for the hydrophobic polyanhydrides over several months. The drug release profile of the model drug p-nitroaniline followed closely that of the degradation of injection-molded poly[bis(p-carboxyphenoxy) propane anhydride] over a period of more than 8 months. Close correlation of polymer degradation and drug release was also observed in other injection-molded samples (10% loading), suggesting a release mechanism that was dominantly degradation controlled. Degradation of these polyanhydrides was pH sensitive, being enhanced in high pH, and became more stable in acidic conditions.
基于多种芳香族和脂肪族二元羧酸的聚酸酐被开发用作可控释放应用的生物可蚀性载体基质。酸酐键的高水解反应活性在降解速率的通用性和控制方面比其他类别的生物可蚀性聚合物具有内在优势。例如，以聚[双（对羧基苯氧基）烷酸酐]为模型，通过将烷烃从甲基变为己基，获得了降解速率在10（-1）至10（-4）mg/h/cm2范围内的聚合物。这些聚合物通过红外（IR）、差示扫描量热法、凝胶渗透色谱法和扫描电子显微镜（SEM）进行表征。在几个月的时间里，疏水性聚酸酐呈现出近零级降解动力学。模型药物对硝基苯胺的药物释放曲线在超过8个月的时间里与注塑成型的聚[双（对羧基苯氧基）丙烷酸酐]的降解曲线密切相关。在其他注塑样品（负载量为10%）中也观察到聚合物降解与药物释放的密切相关性，表明释放机制主要受降解控制。这些聚酸酐的降解对pH敏感，在高pH下增强，在酸性条件下更稳定。
