Exploring The Effects Of Architectures Of PH-Responsive Glycopolymers On Loading And Controlled Release Behavior Of Doxorubicin

Recently, various pH-responsive block glycopolymers have been used in drug delivery research as they can be effective deliver drug to a target site area, and thus increase the therapeutic benefit, while minimizing side effects. The p H-responsive block glycopolymers can self-assemble into core-shell micelles. Hydrophobic core can be loaded with poorly water soluble drugs, and hydrophilic shell give micelle stability and water solubility.The main objective of this research is to explore drug loading and release behavior of pHresponsive block glycopolymers micelles with different architectures used as anticancer drug delivery carriers, for loading and controlling the release with DOX as an anticancer drug.Series of different components and architectures of pH-responsive block glycopolymers micelles bearing random and block architectures by fixing similar each block of degree polymerization(DPs), PEG113-b-P(DEA55-co-GAMA12), PEG113-b-PDEA55-b-PGAMA15, PEG113-b-P(DEA40-co-GAMA30), PEG113-b-PDEA41-b-PGAMA34, and PEG113-b-PGAMA32-bPDEA38 respectively, were successfully synthesized via atom transfer radical polymerization(ATRP). Proton Nuclear Magnetic Resonance(1H NMR) and Gel Permeation Chromatography(GPC) used to characterize their structures, their self-assembly behaviors and drug loading and release behavior of DOX as the model of anticancer drug. The pH-responsive glycopolymers after loading drug were further investigated in detailed by Transmission Electron Microscopy(TEM), Dynamic Light Scattering(DLS), Zeta-potential, and Ultraviolet-visible spectrophotometer(UVVis). The results demonstrate that synthetic pH-responsive block glycopolymers can be dissolved molecularly in aqueous solution at weakly acid p H conditions. While these glycopolymers at pH 10 self-assembling into micelles block copolymers with hydrophobic core and hydrophilic shell. Thus, PEG-b-(PDEA-co-PGAMA) can self-assembly to PDEA-co-PGAMA nuclear as a core, and PEG as the outer shell, reversibly converts to be a two-layer micelles. PEG and PGAMA blocks soluble in water over the entire pH range. Similarly, block copolymer of PEG-b-PDEA-b-PGAMA and PEG-b-PGAMA-b-PDEA were self-assembled to form PDEA as a core, and two layers with PDEA as kernel and PGAMA as the inner shell, the micelle looks like "Onion shape" three-layers. These glycopolymers make self-assembling into micelles at basic conditions, and dissociate to be unimers at acidic conditions. This pH-responsiveness endows block glycopolymers micelles to possess the ability for loading the DOX at physiological condition(pH 7.4) and smart release at mimicking tumor acidic environments(pH 5.5). Furthermore, glycopolymer bearing PEG113-bPGAMA32-b-PDEA38 block architecture exhibits highest critical micellar concentration(CMC), with small size of micelle, and possesses lowest drug release profiles compared with glycopolymers with PEG113-b-PDEA55-b-PGAMA15, PEG113-b-PDEA41-b-PGAMA34, block architectures and PEG113-b-P(DEA55-co-GAMA12), PEG113-b-P(DEA40-co-GAMA30) random architectures respectively. The pH-responsive block glycopolymers are soluble in water media as a weak cationic polyelectrolyte due to protonation of its tertiary amine groups below pH 6, and then converted to be micelles at pH 10. The CMC difference, 0.05, 0.005, 0.01, 0.011, and 0.012 mg/m L, for the block glycopolymers is due to their chemical structures. For the water solubility of GAMA in DEA-co-GAMA block, prevents the self-assembly of DEA block at basic condition and then improves the CMC of aqueous solution. Loading efficiencies are 58, 52, 47.3,47, and 58%, and loading capacities are 12, 10.4, 9.5, 9.3, and 12% of PEG113-b-P(DEA55-co-GAMA12), PEG113-b-PDEA55-b-PGAMA15, PEG113-b-P(DEA40-co-GAMA30), PEG113-b-PDEA41-bPGAMA34, and PEG113-b-PGAMA32-b-PDEA38, respectively. The drug is mainly located in the core of the micelles. Drug release studies presented the complete release of drug from the micelles happens after 240 hours. The result showed the release rate is influenced by glycopolymers composition, micelles size, and encapsulation efficiency.This study displays the self-assembly of pH-responsive block glycopolymers with different architectures by fixing similar DP of their blocks, to design novel drug delivery carriers for loading and controlled release behavior of DOX.