The Novel Temperature And PH Sensitive Dendrimer As Carriers Of Hydrophobic Drugs

Poly(amidoamine) dendrimers are effective drug carriers with properties likebiocompatible, non-immunogenic, biodegradable and so on. Connecting functionalgroups to the surface of structure can make the polymer obtain new performance. Inthis essay, the thermosensitive functional monomers were grafted to the surface ofPAMAM, the product G2.5/3.5PAMAM-Tris-DEAOBA obtained were temperatureand pH sensitive dendrimers.Firstly, ethylenediamine and methyl acrylate were used as material, by repeatedMichael addition reaction and amidation reaction, the ester group-terminated G2.5/3.5PAMAM were synthesized. Then using anhydrous potassium carbonate as catalyst,trihytdroxy methyl aminomethane (Tris) was grafted to G2.5/3.5PAMAM byamidation reaction, getting G2.5/3.5PAMAM-Tris. Using diethylamine and succinicanhydride as material， by amidation reaction the thermosensitive functionalmonomer DEAOBA was synthesized. Finally, using DMAP as catalyst, and EDC·HClas coupling and dehydrating agent, thermosensitive functional monomer DEAOBAand G2.5/3.5PAMAM-Tris were covalent crosslinking by esterification reaction, andthe final product G2.5/3.5PAMAM-Tris-DEAOBA was synthesized, and it wascharacterized by1H-NMR and FTIR.UV-visible spectrophotometry was used to determine the temperature and pHsensitivity properties of the PAMAM derivative. With the increasing of temperatureunder certain pH, the solubility of the polymer declined, and exhibited the lowercritical solution temperature (LCST), which was reduced as the pH and generationdiminished.DL-a-Tocopherol acetate was used as model drug to study the drug loadingproperty of the polymer, drug loading efficiency was determined by fluorescencespectrophotometry, which was increasing with increasing of the pH value andgeneration of the dendrimer. Results of the hemolysis test indicated that the PAMAMderivative was not hemolytic. Because of the biodegradable feature, drug loading inthe carriers could release rapidly, and it could be controlled by adjusting thetemperature or pH condition of the environment.These results indicate that G2.5/3.5PAMAM-Tris-DEAOBA is novel temperature and pH sensitive dendrimer. As smart drug carrier, it will has a goodapplication prospect.