Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG-anhydride-drug linkages
Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG-anhydride-drug linkages
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DOI：
10.1016/s0168-3659(00)00303-5
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发表时间：
2000-11-03
影响因子：
10.8
通讯作者：
Hoffman, AS
中科院分区：
文献类型：
--
作者：
Lele, BS;Hoffman, AS
我们设计了一种新的粘膜粘附药物递送制剂，该制剂基于聚（丙烯酸）（PAA）或聚（甲基丙烯酸）（PMAA）与聚（乙二醇）（PEG）的氢键复合物，即（PEG）-药物缀合物。聚乙二醇化的前药用可降解的PEG-酸酐-药物键合成，用于最终从制剂中递送游离药物。在这项工作中，我们使用吲哚美辛作为模型药物，其通过酸酐键与PEG聚乙二醇化。该复合物首先被设计为当制剂在pH 7.4下与粘膜表面接触时溶胀而解离，释放PEG-吲哚美辛，然后PEG-吲哚美辛水解以释放游离药物和游离PEG。我们发现，随着PAA分子量的增加，复合物的解离速率降低，这导致药物释放速率降低。另一方面，从单独的PEG-吲哚美辛和PEG-吲哚美辛+PAA的固体混合物中的药物释放比从H-键合的复合物中的药物释放快得多。由于热稳定性的差异，PMAA复合物表现出比具有可比MW的PAA复合物略快的药物释放。这些可降解的PEG化药物与生物粘附聚合物的氢键复合物应该可用于粘膜药物递送。(C)2000 Elsevier Science B.V.保留所有权利。
We have designed a new mucoadhesive drug delivery formulation based on H-bonded complexes of poly(acrylic acid) (PAA) or poly(methacrylic acid) (PMAA) with the poly(ethylene glycol) (PEG), of a (PEG)-drug conjugate. The PEGylated prodrugs are synthesized with degradable PEG-anhydride-drug bonds for eventual delivery of free drug from the formulation. In this work we have used indomethacin as the model drug which is PEGylated via anhydride bonds to the PEG. The complexes an designed first to dissociate as the formulation swells in contact with mucosal surfaces at pH 7.4, releasing PEG-indomethacin, which then hydrolyses to release free drug and free PEG. We found that as MW of PAA increases, the dissociation rate of the complex decreases, which results in decreased rate of release of the drug. On the other hand, the drug release from PEG-indomethacin alone and from solid mixture of PEG-indomethacin+PAA was much faster than that from the H-bonded complexes. Due to the differences in the thermal stability, PMAA complex exhibited slightly faster drug release than that of the PAA complex of comparable MW. These H-bonded complexes of degradable PEGylated drugs with bioadhesive polymers should be useful for mucosal drug delivery. (C) 2000 Elsevier Science B.V. All rights reserved.