The Research On The Preparation Of Temperature/pH-sensitive Copolymer Materials And The Release Behavior Of Its Load Paclitaxel

In recent years, the stimuli-sensitive polymeric micelles have received extensive attention and actively investigated for the preparation of intelligent drug carriers in biomedical application in the past several decades. When the body has inflammation or malignant tumour, the pH value would decline in this area. At the same time, the temperature is higher than normal tissue. Thus, properly designed carriers that are dual-responsive to both temperature and pH may be able to intelligently distinguish between normal and pathological tissues, achieving better targeting and treatment efficacy. In this paper, poly(methyl methacrylate)-b- (poly(crylic acid)-b-poly(N-isopropylacrylamide)) (PMMA-b-(PAA-co-PNIPAM)) which has a core-shell structure with the hydrophobic inner core (PMMA) and the hydrophilic shell (PNIPAM) is prepared by reversible addition-fragmentation transfer (RAFT) radical polymerization. The block copolymer (PMMA-b-(PAA-co-PNIPAM)) comprised PNIPAM as the Thermo- sensitive block and PAA as pH-sensitive block.The products are characterized by FT-IR,1H NMR spectra, TEM and GPC. The copolymers can undergo supramolecular self-assembly to thermo-response nanosized micelles in aqueous media. The sizes of the micelles are determined by transmission electron microscopy (TEM), granularity analysis and dynamic light scattering instrument (DLS). The micelles are regularly spherical in shape with an average hydrodynamic diameter around 200 nm. The lower critical solution temperature (LCST) of the copolymer which is higher than PNIPAM is measured by UV-vis and differential scanning calorimetry (DSC). The LCST is decreased by reducing the pH and which can adjust by changing the ratio of the A A and NIPAM, temperature and pH.We also study the drug delivery behaviors of the embedding of this anti-caneer drug paclitaxel (PTX) micelles in a simulated human body environment. The release speed and quantity of the micelles in natural body temperature (37℃) and malignant temperature (40℃) are more than 25℃. This block polymer have double sensitivity of temperature and pH, and it has a potential application prospect in the aspect of Drug slow-release.