Preparation And Characterization Of PH-Sensitive Polymeric Fibers

Various pH gradients exist in tumor growth, inflammation, myocardial ischemia or in the gastrointestinal system. In recent years, synthetic or natural polymers containing acid-responsive groups have been used in drug delivery system to achieve acidity-sensitive feature based on the ionization or protonation of the weakly acidic group(carboxyl) or weakly basic group(amino) in the acidic conditions. Anotherstrategy is to obtain pH-labile linkages(such as cis-aconityl amide, hydrazone and acetal group) in the formulation chain segment, which are disrupted under acid environment resulting drug release. Electrospinning is a technique for preparing long fiber in micrometer or nanometer level. The fibrous membrane has large specific surface area and porosity. Electrospinning fibers as a carrier of drug delivery system, can realize the local release of drug, and is a kind of potential implanting preparations for the treatment of cancer, wound infection. But there are few reports on polymer fibers containing acid sensitive groups in the molecular backbone, where release behaviors respond to the local environment and fiber characteristics.In the current study, a novel strategy was presented to synthesis biodegradable pH-sensitive polymers containing cis-aconityl amide bond and 2,3-disubstituted maleic amide group. Firstly,2-propionyloxy-3-methlymaleic anhydride(CDMwas synthesized and characterized by’HNMR. CDM) and cis-aconityl anhydride (CA) were reacted with diamino poly(ethylene glycol) to synthesize pH-labile CDM/PEG and CA/PEG containing cis-aconityl anhydride, respectively. In vitro degradation tests showed CDM/PEG was more pH-labile than CA/PEG. Then copolymerization of CDM/PEG with D,L-lactide (D,L-LA) was conducted under 140℃with the ratios of 1/4,1/5 and 1/6 to obtain triblock copolymers CDM/PELA-4, CDM/PELA-5 and CDM/PELA-6, respectively. Electrospinning of above polymers were performed to obtained fibers with round-shaped, randomly arrayed and an average size of 1.3 μm. In vitro degradation behaviors were evaluated under pH 5.5, pH 6.5 and pH 7.4 with respect to the mass loss, morphological change, reduction of molecular weight of matrix polymers. Electrospun fibers containing acid-labile segments were stable in neutral buffer solution, but the morphological changes and mass loss of fibrous mats were more significant under acid circumstances and matrix polymer containing higher amount of CDM/PEG.