The Preparation Method And Application Of Acid-sensitive Amphiphilic Block Copolymer

Stimuli-responsive nanoparticles and nanocapsules have attractedintense interest due to their great potentials for various applications. Suchnanosized capsules are able to encapsulate and protect various drugs thatare then released inside cells after the micelles are internalized.Stimuli-responsive polymeric micelles have emerged as vehicles for smartdrug delivery based on which the release of drugs can be readilymodulated by exerting an appropriate stimulus such as temperature, pH,glucose, glutathione, etc. Stimuli-responsive release of drugs may result insignificantly enhanced therapeutic efficiency and minimal side effects.Among available stimuli, change of acidity is particularly appealing due tothe moderately acidic environments in tumor and inflammable tissues aswell as in intracellular compartments such as endosomes and lysosomes.Tumoral pH vairation has been considered as an ideal tirgger foraccomplishing tumor-targeted drug delivery based on the controlledrelease of anticancer drugs in tumor tissues and/or within tumor cells. Upto now, a number of acid-cleavable covalent linkages including acetal， orthoester, hydrazone, imine, cis-acotinyl and oxime have been adopted inthe design and application of pH-sensitive polymeric drug carriers. Whileencouraging progress has been made in this field, new strategies that leadto futrher improvement on the responsive acuteness of the correspondingdrug delivery systems are still in high demand.Amphiphilic block copolymers containing a pH-responsive linkagebased on the tetrahydropyran (THP) moiety were prepared. These blockcopolymers self-assemble into nanosized polymeric micelles in aqueousmedia. The hydrophobic core of the resultant micelles consists ofpoly(lactic acid)(PLA) segments, while the hydrophilic shell is composedof poly(ethylene glycol)(PEG) segments. Results from transmissionelectron microscopy (TEM) and dynamic light scattering (DLS) analysisshow that the micelles have a uniform size, with a mean hydrodynamicdiameter of about20-50nm. As a model drug, doxorubicin (DOX) wasencapsulated into the micelles，with a good drug-loading content (DLC)(PLA-THP-PEG:13.02%). Moreover, the drug release behavior of thesepolymeric micelles were pH dependent, and the cumulative releaseamount of DOX of PLA-THP-PEG micelles were60%at pH5.0，which isabout four times higher than that at pH7.4. While the cumulative releaseamount of DOX of PLA-THF-PEG micelles were69%, little higher than PLA-THP-PEG micelles. DOX encapsulated in the micelles exhibitedexcellent stability under physiological condition (pH7.4). When uponinternalization into cancer cells, the micelles were found to decomposedue to the cleavage of the pH-sensitive linkages under the acidicintracellular environment, which initially led to the release of DOX. Thesefindings indicate that polymeric micelles described here should offer aneffective approach ofr drug delivery.