Quaglia Fabiana, Vignola Maria, De Rosa Giuseppe, La Rotonda Maria, Maglio Giovanni, Palumbo Rosario
Department of Pharmaceutical and Toxicological Chemistry, University of Napoli Federico II, Via D. Montesano 49, Napoli, Italy.
J Control Release. 2002 Oct 4;83(2):263-71. doi: 10.1016/s0168-3659(02)00208-0.
Segmented poly(ether-ester-amide)s (PEEAs) derived from poly(epsilon-caprolactone) oligomers, sebacoyl chloride, hydrophilic diamide-diamines based on short sequences of ethylenoxy groups and containing amino acids, were used to produce matrix systems intended for the delivery of metronidazole in the periodontal pocket. PEEAs are soluble in chloroform and insoluble in water and show M(n) values in the range 8.5-18.6 kDa. The melting temperatures (53-59 degrees C) are close to that of poly(epsilon-caprolactone) (PCL) with a similar M(n). The water absorption of PEEAs is improved if compared with that of pure PCL and depends on both the length of oxyethylene sequences and the amino acid number, as well as on copolymer composition. Loaded-films containing 20% (w/w) of metronidazole were prepared by compression-molding. The release rate was diffusive in the first stage, whereas also other mechanisms, probably polymer degradation, contributed to the slower second phase. The rate of medium penetration within the film depended on PEEA hydrophilicity and crystallinity and was the main determinant governing the drug release rate. The opportunity to control effectively drug release rates by modulating the composition, and in turn the properties, of PEEAs is an attracting feature for their use in a number of drug delivery systems.
由聚（ε-己内酯）低聚物、癸二酰氯、基于短序列亚乙基氧基且含有氨基酸的亲水性二酰胺二胺衍生而来的嵌段聚（醚-酯-酰胺）（PEEA），被用于制备旨在将甲硝唑递送至牙周袋的基质系统。PEEA可溶于氯仿，不溶于水，其数均分子量（M(n)）值在8.5 - 18.6 kDa范围内。其熔点温度（53 - 59℃）与具有相似M(n)的聚（ε-己内酯）（PCL）相近。与纯PCL相比，PEEA的吸水性有所提高，且取决于氧化乙烯序列的长度、氨基酸数量以及共聚物组成。通过压缩模塑制备了含有20%（w/w）甲硝唑的负载膜。释放速率在第一阶段为扩散型，而在较慢的第二阶段，可能还有其他机制（可能是聚合物降解）起作用。介质在膜内的渗透速率取决于PEEA的亲水性和结晶度，是控制药物释放速率的主要决定因素。通过调节PEEA的组成进而调节其性质来有效控制药物释放速率的可能性，是其在许多药物递送系统中应用的一个吸引人的特性。
