Study On Drug Solubilization And Release Of Dendrimer And Its Thermo-sensitive Derivative

Dendrimers are synthetic, highly branched molecules of nanometer dimensions. Properties associated with dendrimers such as uniform size, water solubility, modifiable surface functional groups and available internal cavities make them attractive for drug-delivery applications.A novel dendrimer derivative combining the temperature-sensitivities ( PNIPAAm, poly-N-isopropylacrylamide) was synthesized. First of all, PAMAM dendrimers was synthesized on the basis of repeatedly using two consecutive chain forming reactions, the exhaustive Michael addition reaction and the exhaustive amine reaction. Then the PAMAM dendrimer derivatives (PAMAM-g-PNIPAAm) with thermo-sensitive grafts on the surface can be synthesized via amidation reaction.Using indomethacin as a model drug, the study of dendrimer solubilization capacity on hard-dissolved guest molecule was discussed emphatically. The ability of dendrimers to increase the solubility of hydrophic drug molecules was investingated by UV-VIS spectroscopy. The dendrimers and its thermo-sensitive derivatives all enhanced the solubility of model drug significantly. And in a certain range, solubility of indomethacin improve with the increase of concentration of dendrimersThe behaviors of the temperature controlled drug release from this novel polymer have been studied. In vitro release profile of indomethacin from dendrimers and PAMAM-g-PNIPAAm was examined at different temperature. While the LCST (Lower Critical Solution Temperature) of PAMAM-g-PNIPAAm is 34.3℃, much more indomethacin release from the complex at 27℃than at 37℃. So the rate of the drug release can be effectively controlled by the surrounding temperature.This novel dendrimer derivative was improved to increase the solubility of indomethacin and control the release the drug, which provides a novel method to solubilization and control release for other hydrophobic drugs.