Synthesis Of Poly(Glycerol Methacrylate)s Carboxylic Derivatives For The Controlled Release Of Doxorubicin

In recent years, dendrimers have aroused great concern due to their unique architectureand properties. These macromolecules have precise structures, a high degree of geometricsymmetry, a well defined number of peripheral groups and internal cavity with a controlledmolecular weight, their peripheral groups could be functionalized with drugs, targetingmoieties, etc. Dendrimers hold promise as a novel of drug delivery vehicle.In this study, a series of liner and star-shaped poly(glycidyl methacrylate)s (PGMAs)with different molecular weight were synthesized by atom transfer radical polymerization(ATRP). Afterwards, poly(glycerol methacrylate)s (PGOHMA) was obtained through thehydrolysis of the epoxy ring of PGMA. Different anhydrides such as succinic anhydride and 1,2-cyclohexanedicarboxylic anhydride were used to modify them to result in pH-responsivePGOHMACOOHs. Esterification rates were adjusted by the feeding ratio of anhydride.Polymers with different pH-responsive range were obtained. The surface hydroxyl groups ofPGOHMACOOHs were crosslinked with hexamethylene diisocyanate (HDI) to getPGOHMACOOH-HDI. The cross-linking did not change the original pH-responsiveproperty. The polymers were characterized by infrared spectrometer (FT-IR),cross-polarization/magic-angle spinning (CP/MAS13C NMR), nuclear magnetic resonancespectrum (1H NMR), gel permeation chromatography (GPC), etc.The esterification rates of PGOHMACOOHs and PGOHMACOOH-HDIs were measuredby pH titration, during the titration procedure we observed that the solution changed fromclear to turbid and it was reversible. These two types of polymers could form nanoparticlesthrough dialysis method. Thire particle size was ranging from 100 to 200 nm measured bydynamic light scattering (DLS). The cytotoxicity assay indicated the cytotoxicity ofPGOHMACOOH-HDIs was very low, to some extent the polymer could accelerate cellgrowth.The anti-cancer drug doxorubicin was used to evaluate the encapsulation and releaseproperties of the obtained polymers. Loading capacity (LC) and encapsulation efficiency (EE)of the S8-PGOHMA-CDA with high carboxyl replacement could reach 15.15% and 75.75%.The encapsulated doxorubicin was released nearly 95% at pH 4.0 within 30 h. While at pH5.5 and 7.4 only 20% and 33% of doxorubicin released, respectively. For the cross-linkedpolymer PGOHMACOOH-HDI, the LC and EE of doxorubincin was improved, the highestLC and EE could reach 49.96% and 99.98%, respectively. And the release rate could be moreeffectively controlled at pH 4.0 and 7.4.