Synthesis And Characterization Of Novel Acid-sensitive Polymeric Drug Carriers

AbstractIn this paper, two kinds of acid sensitive compounds(a methacrylamide monomer and a diamido monomer) was synthesized using diglycerol and triethoxy methane, and all of them contained two five-membered ortho ester rings, used as a cross-linker or monomer of PEG-b-PMEA. At the same time, PEG-b-PNSM was synthesized using methacrylic acid N-succinimidyl ester(NSM), then1 H NMR and gel permeation chromatography(GPC)were used to verify these two polymers.Critical micelle concentration(CMC) was measured through fluorescence spectroscopy,and then found that both PEG-b-PMEA and PEG-b-PNSM micelles have a low CMC(PEG-b-PMEA: 9.0×10-4~5.0×10-3g/L; PEG-b-PNSM: 6.0×10-4~7.0×10-3g/L) and good stability. After adding p H-sensitive cross-linker, PEG-b-PNSM micelles became to the acid-sensitive core-crosslinked micelles. Acid sensitivity, particle size distributions of PEG-b-PMEA micelles and the core-crosslinked micelles as well as changes in different p H solutions were characterized by NMR and dynamic light scattering(DLS), then found both novel micelles containing ortho ester rings were degradable in slightly acidic environment and the change of particle size had a different with each degradation products of micelles.Hydrophobic Nile red as a model drug was encapsulated into two micelles, respectively. Nile Red-loaded micelles could be effectively embedded and p H-responsive release of Nile Red. In vitro cytotoxicity test indicated that PEG-b-PMEA micelles and PEG-b-PNSM micelles as well as its core-crosslinked micelles had a good biocompatibility. The Paclitaxel-loaded PEG-b-PMEA micelles showed similar potency in killing human lung cancer cells(A549),and the Paclitaxel-loaded PEG-b-PNSM core-crosslinked micelles had potency in killing human breast cancer cells(MCF-7), compared with the free PTX, respectively. And the uptake of Nile Red-loaded core-crosslinked micelles into MCF-7 cells was examined using confocal laser scanning microscopy.In summary, both novel p H-sensitive PEG-b-PMEA and the core-crosslinked micelles could be used as good drug delivery carriers for hydrophobic drugs.