Preparation And Properties Of Drug Controlled Release Of The Self-assembled Carriers Based On Ionic Amphiphilic Polymers

The survey and development of drug carrier materials was reviewed.The ionic carriers were prepared and the drug release behaviors of these carriers were studied.The derivatives of poly diallyl dimethyl ammonium chloride(PDDA),thermo-responsive polymer poly(N-isopropylacrylamide)(PNIPAM)and degradable poly(lactic acid)(PLA)with special terminal groups were synthesized in the study.Drug carriers with multiple environment-responsing properties,for example ionic responsive,thermos-responsive and biodegradable properties,were prepared based on the self-assembly performances of those polymers.We investigated the major factors which affected on the structures of the formed carriers and the responsive drug release behaviors.Using prednisone acetate(PA)as a model drug,the drug release properties of PDDASA and PDDASA/PNIPAM carriers were studied.The performance of the drug encapsulation and release behaviors of Dox · HC1 from PLA-based carriers,including PLA/PDDASA,PLA/PNIPAM and PLA/PNIPAM/PDDASA were also investigated.Poly diallyl dimethyl ammonium chloride(PDDA(C1))was transformed into its hydroxide(PDDA(OH))through an ion exchange method,and then stearic acid(SA)segment was introduced into the hydroxide polymer by a simple acid-base reaction,an amphiphilic ionic polymer PDDASA was synthesized finally.Thermo-responsive polymer PNIPAM-COOH with carboxyl terminal group was synthesized by a free radical polymerization.An ionic polymeric vehicle was obtained after self-assembling and subsequent ion/chemical crosslinking of PDDASA in the interface between oil and water phase.The thermo-responsive carrier PDDASA/PNIPAM was fabricated in the same system excepting introduction of PNIPAM-COOH.Using PA as a model drug,PA-incorporated carriers were prepared and drug release behaviors were studied.The results showed that these carriers presented a hollow-capsule structure and notable sustained-release property.Temperature and pH changes didn’t show effect on the drug release from PDDASA carriers.However,PDDASA/PNIPAM carriers demonstrated obviously temperature-responsive property;the drug release rate and cumulative release were significantly increased with the temperature increase.Meanwhile,pH increase also had impacts on the drug release rate and cumulative release from PDDASA/PNIPAM carriers.Aminated cyclodextrin was synthesized from β-CD.The CD-modified PNIPAM(PNIPAM-CD)was obtained by an acid amine condensation between amino cyclodextrin and PNIPAM-COOH.Lactide was synthesized by a polyconsederation-pyrolysis under catalyst.Adamantane-ended poly(lactic acid)(PLA-Ad)with three different molecular weight were synthesized by a ring opening polymerization of lactide using 1-adamantanol as initiator.The structure of these polymers were characterized by infrared spectroscopy(FT-IR)and nuclear magnetic resonance(NMR)characterization.The molecular weight of the polymer PLA-Ad was quantitatively determined by 1HNMR.Multiple-responsive carriers were prepared by self-assembly of the formed polymers of PLA-Ad,PDDASA and PNIPAM-CD.The properties and drug release behaviors of Dox·HC1-encapsulated carriers were studied.The prepared carriers showed hollow structure and excellent sustained-release capability with a particle size was in the range 0.3-0.8 pm.The carriers of PLA/PDDASA and PLA/PNIPAM/PDDASA demonstrated significantly pH-responsive release ability.In the study,reliable multi-responsive carriers of ionic polymer were prepared by self-assembly of ionic polymer after introducing thermos-responsive and degradable polymers.These carriers have good comprehensive performance,and also show better sustained release and responsive performance,which presents great potential in the aspect of biomedical material and drug delivery.