Studies On The Synthesis And Properties Of PH-Responsive Polymers For Drug Delivery

In this study, we are reporting the synthesis of two types of acid-labile block copolymers. One kind is the polymer with structure with ketal which include acetone, cyclopentanone and 2-pentanone, another kind is the polymer with structure with orthoester. Atom transfer radical polymerization (ATRP) of monomer using a poly (ethylene glycol) (PEG) macroinitiator afforded acid-responsive block copolymers. Their chemical structures were characterized by 1H NMR,13C NMR and gel permeation chromatograph (GPC). The critical micelle concentration (CMC) was estimated by fluorescence spectrometer using pyrene as molecule probe. These results indicated that the longer the hydrophobic chain length, the lower the CMC. Both the sizes and morphologies of the micelles were determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). pH-dependent destabilization of the polymeric micelles was studied by using Nile Red fluorescence. The results demonstrated that hydrophobic Nile Red could be loaded in the micelles that were stable at pH 7.4, but destabilized in mildly acidic media. Polymeric micelles prepared from MPEG-b-PTMDMA were stable at pH 7.4 and pH 5.5, but were prone to slowly hydrolysis at acidic pH of 3.5. pH-dependent destabilization of the polymeric micelles was studied by using light scattering, The ketal hydrolysis resulted in significant swelling of micelles, from 100 nm to 1000 nm, as a result of change of hydrophobic polyketal to hydrophilic polyketal. Polymeric micelles prepared from MPEG-block-PEODMA were stable at pH 7.4, but rapid hydrolysis at acidic pH of 2.5 and 3.5, The dissociation of the micelles and the subsequent release of Nile Red were induced by the acid-triggere hydrolysis of the ketal/orthoester groups, which causes the polarity transfer from amphiphile to double hydrophile for these copolymer. Hydrolysis of the ketal/orthoester groups was proved by the 1H NMR spectra and FT-IR. These pH-responsive biodegradable micelles having good encapsulation efficiency for hydrophobic drugs are potential candidates for biomedical and targeted delivery of anticancer drugs.