The Study For Drug Release Systems Of Photothermal Responsive Hollow Mesoporous Carbon Nanoparticles

Objective:In this study,based on the inorganic hollow mesoporous carbon nanocarrier with photothermal transformation ability,the efficient and stable drug loading was realized through its macroporous cavity and appropriate pore size.The temperature sensitive polymer poly（N-isopropylacrylamide）was used to functionalize the carrier,and the photothermal stimulation response intelligent controlled release drug was realized.The interaction between hollow mesoporous carbon and temperature sensitive polymer is affected by many factors and has multiple regulation on the release behavior of loaded drugs.Therefore,the comprehensive evaluation of hollow mesoporous carbon photothermal stimulus response system control precision drug release factor,build relationship model of effect of drug release law between hollow mesoporous carbon photothermal stimulus response system and interpretation environment parameters,the model"temperature sensitive polymer-drug release systems of photothermal responsive hollow mesoporous carbon nanoparticles-drug release law"is of great significance.Methods:The hollow mesoporous carbon nanoparticles（HMCNs）were prepared by the soft membrane method,and the HMCNs were oxidized under acidic conditions with ammonium persulfate to obtain carboxylated hollow mesoporous carbon nanoparticles（HMCNs-COOH）,which were obtained by transmission electron microscopy（TEM）,Brunauer–Emmett–Teller（BET）,Fourier transform infrared absorption spectrometer（FTIR）and other means to characterize the carrier’s appearance,pore structure,pore size,particle size,and surface groups;Empagliflozin is loaded using the solvent evaporation method,ultraviolet spectrophotometer（UV-vis）for drug loading calculation,X-ray diffractometer（XRD）and TEM for the characterization of the drug existence form.Thermo-sensitive copolymers with different low critical solution temperatures（LCST）were synthesized by free radical polymerization,sucn as poly（N-isopropylacrylamide）（PNIPAM）,N-isopropylacrylamide and acrylamide copolymer（P（NIPA-AM））,N-isopropylacrylamide and allylamine copolymer（P（NIPA-AL））.The Zeta potential of the polymer at different p H was determined.The positive and negative polyelectrolytes were modified to the exterior of carbon nanoparticles by layer by layer electrostatic self-assembly method,and the morphology and properties of hollow mesoporous carbon photothermal response drug loading system were characterized by FTIR,TEM and photothermal experiment.Four factors and five levels central composite design（CCD）were used to construct the drug release model of HMCNs among drug carrier,polymer and drug release conditions.The four factors were drug loading（A）,number of polymer layers（B）,dissolution temperature（C）and dissolution revolution（D）.The response values were 1 h cumulative release（Y₁）,24 h cumulative release（Y₂）and release rate constant k（Y₃）,respectively.Response surface and mathematical model were established according to the dissolution results of CCD experimental group in vitro.The response surface results were systematically analyzed to investigate the effects of drug loading,polymer layer number,dissolution temperature and dissolution revolution on drug release behavior and their interactions.Results:TEM and BET results show that HMCNs with a hollow cavity of 200 nm,a shell thickness of about 40 nm and a pore size of about 4 nm have been successfully prepared.FTIR and water dispersibility experiments show that the carboxylation of HMCNs has been successfully achieved.The model drug empagliflozin was successfully loaded into HMCNs-COOH by solvent evaporation method.The measured drug loading increased with the increase of the prescription ratio.TEM and XRD results showed that the drug was partially loaded into the cavity of the carrier and partially attached to the pores and channels.On the surface of the carrier,the external crystals increase with the increase of the drug loading.The LCST results of temperature-sensitive polymers synthesized with different copolymer monomers and different ratios show that the more hydrophilic amide groups or amine groups are introduced,the LCST of the polymer increases significantly,and the more hydrophilic groups are introduced.Larger,the greater the LCST of the synthesized polymer;Zeta potential results show that the surface of HMCNs-COOH in the aqueous solution is negatively charged,P（NIPA-AM16）is slightly negatively charged,and P（NIPA-AL17）is strongly positively charged.FTIR、XPS and TEM images of the hollow mesoporous carbon photothermal response drug carrier system show that the polymer is successfully modified on the surface of the carrier;the heating curve under near-infrared light shows that it has photothermal conversion properties;the in vitro release results show that the cumulative release of 1 h is reached in the stable phase,several mathematical models that conform to the drug release were fitted,and it was found that when the Ritger-Peppas model was used to fit,R²was the largest,so we used the Ritger-Peppas model to calculate the rate constant k.Conclusions:The hollow mesoporous carbon photothermal response drug delivery system was successfully prepared,and the release model and response surface of the precise controlled release drug delivery system were constructed using the CCD method.PSS-P（NIPA-AL17）groups:with the increase of drug loading and polymer layer number,the 1h cumulative release Y₁decreased gradually;However,with the increase of temperature,Y₁gradually increases.With the increase of temperature,the 24 h cumulative release Y₂increased gradually.As the number of polymer layers decreased and the number of revolutions decreased,Y₂gradually decreased.With the increase of polymer layer and drug loading,the release rate constant k Y₃decreased gradually.PAA-P（NIPA-AL17）groups:Y₁decreased with the increase of drug loading;However,with the increase of temperature,Y₁gradually increases.With the increase of temperature,Y₂gradually increases.With the increase of polymer layer and drug loading,Y₃decreased gradually.Regardless of the number of polymer layers,the higher the temperature,the higher Y₁and Y₂;with the increase of the number of revolutions,Y₂and Y₃increase.Both models can predict well.