Kolhe Parag, Misra Ekta, Kannan Rangaramanujam M, Kannan Sujatha, Lieh-Lai Mary
Department of Chemical Engineering and Material Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA.
Int J Pharm. 2003 Jun 18;259(1-2):143-60. doi: 10.1016/s0378-5173(03)00225-4.
Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with --OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the --OH end groups and the drugs prevents complex formation.
高度支化的功能化聚合物有潜力充当高效的药物载体系统。树枝状聚合物是模型超支化聚合物中的理想候选者，因为它们具有明确的结构和高密度的官能团。以布洛芬为模型药物，我们研究了该药物与聚酰胺胺（PAMAM）树枝状聚合物（第3代和第4代，具有-NH2官能团）以及Perstrop多元醇（第5代，具有-OH官能团的超支化聚酯）之间的相互作用。傅里叶变换红外光谱（FTIR）和核磁共振（NMR）研究表明，由于-NH2端基与布洛芬羧基之间的离子相互作用，布洛芬主要与PAMAM树枝状聚合物形成复合物。平均而言，一个含有64个端基的PAMAM-G4-NH2分子最多可结合78个布洛芬分子。该复合物在去离子水和甲醇中稳定。与纯布洛芬相比，药物-树枝状聚合物复合物中布洛芬的体外释放明显较慢。复合药物进入A549细胞的速度比纯药物快得多，这表明树枝状聚合物可能能够有效地将复合药物携带到细胞内。超支化多元醇（具有128个-OH端基）似乎能包裹大约24个药物分子。也许-OH端基与药物之间缺乏强相互作用阻碍了复合物的形成。
