Synthesis of poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine) and preparation of its hydrogel solution containing doxorubicin

Many pH- and temperature-responsive polymers have been designed for preparing hydrogel. In the present study, in order to decrease the pH sensitivity of reported poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine) (PAA₁₅₈₀-PEG₄₆₀₀-PAA₁₅₈₀), we designed and synthesized poly(amidoamine)-poly(ethyleneglycol)-poly(amidoamine) (PAA-PEG-PAA) with shorter length of PAA chain by decreasing reaction temperature for preparing PAA-PEG-PAA hydrogel solution containing doxorubicin (DOX). The PAA-PEG-PAA was synthesized via the Michael-addition polymerization. The characteristic of PAA-PEG-PAA was evaluated.The PAA-PEG-PAA hydrogel solution was prepared and investigated. DOX-loaded PAA-PEG-PAA hydrogel solution was prepared, and its in vitro DOX release and in vitro anti-tumor activity were evaluated. Our results indicated that the viscosity of PAA-PEG-PAA hydrogel solution was concentration- and temperature-dependent. The sol-gel transition temperature of PAA-PEG-PAA hydrogel solution (12 %, w/w) ranged from 35 to 29 ºC, and its pH ranged from 6.0 to 7.4. The released DOX from DOX-loaded PAA-PEG-PAA hydrogel showed sustained release characteristics. The in vitro anti-tumor activity of DOX-loaded PAA-PEG-PAA hydrogel was confirmed in B16F10 cell line. Considering the acidic tumor microenvironment, this DOX-loaded PAA-PEG-PAA hydrogel solution would be easy in situ administration for intra-tumor injection or para-tumor injection forming hydrogel at body temperature. We suggested that this DOX-loaded PAA-PEG-PAAhydrogel solution, if containing photothermal conversion agents, would have a potential further use for photothermal therapy.