BIOERODIBLE POLYANHYDRIDES AS DRUG-CARRIER MATRICES .1. CHARACTERIZATION, DEGRADATION, AND RELEASE CHARACTERISTICS
BIOERODIBLE POLYANHYDRIDES AS DRUG-CARRIER MATRICES .1. CHARACTERIZATION, DEGRADATION, AND RELEASE CHARACTERISTICS
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DOI：
10.1002/jbm.820190806
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发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
LANGER, R
中科院分区：
文献类型：
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作者：
LEONG, KW;BROTT, BC;LANGER, R
基于多种芳香族和脂肪族二羧酸的聚酸酐被开发为生物可降解的载体基质，用于控制递送应用。与其他种类的生物可降解聚合物相比，酸酐键的高水解反应性在通用性和降解率控制方面具有内在优势。例如，以聚双（对羧基苯氧基）烷烃酸酐为模型，通过将烷烃从甲基变为己基，得到了降解率在10-1至10-4 mg/h/cm2范围内的聚合物。采用红外（IR）、差示扫描量热法、凝胶渗透色谱法和扫描电镜（SEM）对聚合物进行了表征。在几个月内观察到疏水聚酸酐的近零级降解动力学。在超过8个月的时间里，模型药物对硝基苯胺的药物释放曲线与注射成型聚双（对羧基苯氧基）丙烷酸酐的降解曲线密切相关。在其他注射成型样品中（加载量为10%）也观察到聚合物降解与药物释放密切相关，表明其释放机制主要受降解控制。这些多酸酐的降解对pH敏感，在高pH条件下降解增强，在酸性条件下降解更稳定。
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.