Research On The Responsiveness Of Nano Drug Delivery System And Mobile Drug Delivery System Based On Polyacrylic Acid

In recent years,with the development of pharmaceutics,both of changing the dosage forms of drugs and constructing new drug delivery systems have become the current research hotspots in pharmacy.The intelligent drug delivery system has become one of the important aspects of the drug delivery field which has gained increasing attention among worldwide researchers.Intelligent drug delivery system,also known as stimulusresponsive system,refers to the drug delivery system formed by the close cooperation of different material components.When the systems are stimulated by physical or chemical signals from the environment,their structural characteristics also change accordingly.Researchers design the corresponding stimulus-responsive drug delivery system according to different environmental conditions,which can be used for controlled or sustained release of the drug.However,the two major drug controlled release systems(reservoir type and matrix type)have some drawbacks,which limit the application potential of the controlled release drug delivery system to a certain extent.Therefore,the responsiveness of nano drug delivery system and mobile drug delivery system based on polyacrylic acid was proposed in this paper.The preparation conditions,structure,and morphology,grafted functional monomers and the responsiveness after grafting of polyacrylic acid nanospheres were systematically studied.Based on the hydrogen bonding between polyacrylic acid(PAAC)and polyacrylamide(PAAM),a mobile temperature-sensitive drug delivery model was established to explore the quantitative relationship between the temperature responsiveness of microencapsulation-microencapsulated mobile drug delivery system.In the First Chapter of this paper,the main content introduces the intelligent drug delivery system and discusses the current research status of some stimulus-response drug delivery systems.At the same time,some contents including the current classification of nano-particles,the characteristics,the preparation,and the application of organic polymer nanoparticles were introduced.Finally,the purpose and significance of this paper were put forward.In the Second Chapter of this paper,PAAC nanospheres were prepared by reflux precipitation polymerization in acetonitrile using acrylic acid(AAC)as the monomer,azobisisobutyronitrile(AIBN)as initiator,and N,N-methylene bisacrylamide(BIS)as cross-linking agent.The chemical structures of the nanospheres were identified by FT-IR,XPS,and XRD,The microscopic morphologies of the nanospheres were characterized by TEM and SEM,The effect of various reaction conditions on the particle size of PAAC nanospheres was explored by single-factor orthogonal experiments.The experimental results show that when the monomer concentration was 0.0694 mol/L,the dosage of the crosslinker was 7 wt%(being equivalent to the mass of the monomer),the dosage of the initiator was 2 wt%(being equivalent to the mass of the monomer),and the reaction time was 0.5 h,polyacrylic acid nanospheres with a monodispersity of 0.023 and a particle size of 70-90 nm with certain double bonds remaining on the surface can be obtained.In the Third Chapter of this paper,pH/temperature-responsive PAAC-g-poly(N-isopropylacrylamide)composite nanospheres were prepared based on the Second Chapter.By using the PAAC nanospheres prepared in Chapter 2 with certain residual double bonds on their surface,poly(N-isopropylacrylamide)(PNIPAM)chains were grafted onto their surface by free radical polymerization at room temperature,and their temperature-sensitive,pH-sensitive and reversible stimulus-responsive behaviors were explored by changing the reaction conditions.The experimental results show that the PAAC-g-PNIPAM composite nanospheres had temperature-responsive behavior,and when the temperature increased,the particle size of PAAC-g-PNIPAM composite nanospheres decreased due to the change of the PNIPAM chain segment from the extended state to the contracted collapsed state,and the composite nanospheres had a better reversible response to temperature-based stimulation.Meanwhile,PAACg-PNIPAM composite nanospheres had pH-responsive behavior,with increasing particle size as the pH increases when the pH was greater than 6.0.The main content of the Fourth Chapter of this paper was to continue to explore the construction and release of the mobile "on-off" drug delivery model in the previous research of the research group.The PES-g-PAAC capsule and PES-g-PAAM capsule with different grafting rates were obtained by grafting poly(acrylic acid)or poly(acrylamide)onto poly(ether sulfone)(PES)capsules with figer-like channels.PES-g-PAAC capsules and PES-g-PAAM capsules with different grafting ratios were combined to construct the drug release model of PAAM grafted capsule-PAAC grafted capsule.In the drug release experiment in vitro,vitamin B12 was used as a simulated drug to determine the release amount of vitamin B12 to explored the best combination of grafting rate.The results show that the drug release from the combination was the highest when the graft ratio of PES-g-PAAM capsule to PES-g-PAAC capsule was 0.68-0.8,and the hydrogen bond switching effect of PAAM and PAAC was the most obvious.