Synthesis Of Biodegradable PH-Sensitive Polymers For Control Release Of Drugs

A decrease in local pH often accompanies tumor growth,inflammation,and myocardial ischemia or in the gastrointestinal system.Synthetic or natural polymers containing weakly acidic or basic groups have been used as the pH-sensitive controlled release systems for drug delivery.And the reported pH-sensitivity is based on the ionization or protonation of weakly acidic(carboxyl)or basic(amino)groups. Another strategy is to include pH-labile linkage(such as acetal and hydyne group)in the formulation matrices,which are disrupted under acid environment resulting drug delivery and stable in neutral circumstance.But these polymers contain one or more nondegradable chains.Electrosinning is a technology for preparation long nano- or micro-fibers.The porous structure of fibrous mat led to high porosity and large surface aera.The local delivery and controllable release profiles make electrospun ultrafine fibers as potential implantable drug carriers and functional coatings of medical devices.There are few attempts to form acid-labile electrospun fibers,whose 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 ortho ester groups.Firstly, 3,9-dimethylene-2,4,8,10-tetraoxaspiro[5.5]undecane(DMTU),one of the important components of poly(ortho ester),was synthesized and chanracterized by FTIR and ~1H-NMR.The acid-labile segments,such as POE_D(containing 1,10-decanediol)and POE_P(containing PEG200)were synthesized through reacting DMTU with 1,10-decanediol and poly(ethylene glycol).FTIR,GPC and ~1H-NMR confirmed the reaction between DMTU and 1,10-decanediol or PEG200 without residual DMTU and diol.In order to make sure the thermostability of POE_D and POE_P during the polymerization step,FTIR spectra were collected under elevated temperatures showing that POE_D and POE_P were stability under 140℃.The further copolymerization of D,L-LA(D,L-lactide)with POE_D and POE_P was conducted under 140℃to obtain triblock copolymers of PLAOE_D(containing 1,10-decanediol) and PLAOE_P(containing PEG200).FTIR and ~1H-NMR results confirmed the structure of PLAOE_D and PLAOE_P.GPC analysis indicated that only one peak was shown in the colpolymer and no residual reactant.Biodegradable pH-sensitive polymers of PLAOE_D and PLAOE_P were electrospun with the encapsulation of paracetamol as a model drug.As shown in the SEM morphologies of electrospun fibrous mats,fibrous mat possessed the common feature of being round-shaped,randomly arrayed,and very porous.There no drug crystals were detected on surfaces of the smooth fiber,indicating that the drug was finely incorporated into the electrospun fibers.Loaded amounts of paracetamol of 1.96±0.2 %,1.94±0.2%and 1.95±0.3%were close to the theoretic values(2.0%,w/w)for all the fiber samples.PDLLA Used as a reference substance,In vitro degradable and drug delivery behavior of fibers were discussed in different pH buffer solution.In vitro release study showed that the total amount of drug released from pH-sensitive polymeric fibers was accelerated after incubation into acid buffer solutions,and the amount of initial burst release and sustained release rate were significantly higher for matrix polymers with hydrophilic acid-labile segments.In vitro degradation study indicated that the electrospun fibers containing acid-labile segments were stable in neutral buffer solution,but the molecular weight reduction of matrix polymers,the morphological changes and mass loss of fibrous mats were significantly enhanced under acid circumstances.