Researches On The Self-Oscillation Drug Delivery System And The Immobilized Quantum Dot For Long-Term Monitoring

Since pharmaceutics entered the era of drug delivery systems（DDS）,different intelligent drug delivery systems were already developed by researchers.Compared with traditional pharmaceutics,these intelligent drug delivery systems have great advantages in increasing the therapeutic effect and reducing the toxic and side effects of drugs.At the same time,the intelligent drug delivery systems can also meet the requirements of on-demand drug delivery and on-time drug delivery of personalized medicine.In the process of research on the intelligent drug delivery systems,the following two questions are worth considering:（a）Most drug delivery systems relying on blood circulation have problems of slow enrichment or release in capillary end tissues or physiological barriers.Maybe a self-oscillating drug delivery system can be constructed to solve the problems.（b）There are few more intuitive ways to observe the distribution,transport,and absorption of drugs or carriers for a long time.Maybe a certain substance can be found to achieve the purpose of long-term monitoring.Based on these issues,this research is mainly divided into the following two parts:The first part:the synthesis of the product of the Belousov-Zhabotinsky（BZ）reaction and gel self-oscillation.By synthesizing the key compound of BZ reaction,and using this compound to participate in the synthesis of hydrogel,the feasibility of transforming chemical oscillation change into mechanical change was studied.The results were hoped to provide ideas for the research of new self-oscillating drug delivery systems.In this chapter,the core compound B of the BZ reaction was synthesized and its structure was confirmed by ¹H NMR spectrum.Through the ultraviolet-visible full-wavelength scanning spectrum and fluorescence excitation/emission spectra,it was determined that the compound had fluorescence characteristics.The optimal excitation wavelength of fluorescence was 566 nm,and the optimal emission wavelength was 630 nm.And it was also discovered that the compound B had no dependence on the change of fluorescence excitation wavelength.Through DCC/NHS or EDC/NHS mediated acylation reaction,the compound B was linked to the single chain polymer of acrylic acid or acrylamide by amide bond.The infrared spectrum analysis results proved the successful introduction of compound B.The polyacrylic acid（C₂）/polyacrylamide（M₂）single chains containing Ru were dissolved in the substrate solution of the BZ reaction,and obvious oscillations were observed.It was different on oscillation period and the transition time of their oxidation state and reduction state between C₂ and M₂.At the same time,the temperature changes were measured with a temperature sensor during the oscillation reaction,it was found that the temperature of the two solution showed a step-like upward trend with the reaction time.The time-temperature change diagram showed that the oscillation of C₂/M₂ was a continuous heating process.In the oscillating experiment of two mixed solutions with different proportions,it was found that the increase of the C₂ ratio would make the oscillating reaction phenomenon more obvious,the reaction period would be slightly longer,and as the ratio of M₂increased,the color change of the oscillation reaction solution and the intensity change of the fluorescence became weaker.Finally,by mixing C₂/M₂ into the gel and putting it into the oscillation reaction solution,it was found that the columnar gel did not show the"oscillation"phenomenon as expected,while the striped gel showed the"oscillation"phenomenon;And the addition of N-isopropylacrylamide（NIPAM）would facilitate the"oscillation"phenomenon.The change of the N-M₂-gel was the most obvious compared with other gels,and there was a mechanical change of bending-recovery.The second part:synthesis and immobilization of polyamine functionalized quantum dots.The quantum dots were modified to immobilize them to overcome the shortcomings of being easily detached from the drug carrier（such as hydrogel）.And they were added to the hydrogels to study the possibility of long-term monitoring.In this chapter,N-doped polyamino-functionalized carbon quantum dots（N-CQDs）were obtained through the one-step hydrothermal method.Then the N-CQDs was modified by methacrylic anhydride.The success of the double bond modification was confirmed by FT-IR and ¹³C NMR spectra.The fluorescence properties of N-CQDs before and after modification were studied by UV-Visible spectrum and fluorescence spectrum.The best excitation wavelength of N-CQDs before and after modification were 365 nm,and the best emission wavelength of N-CQDs was changed from 451 nm to 459 nm after modification;N-CQDs had no dependence on excitation wavelength before and after modification.The fluorescence quantum yield before and after the modification were measured with quinoline sulfate as the standard solution,and it was discovered that the modification increased the fluorescence quantum yield from 16.9%to 26.5%.The N-CQDs before and after the modification were incorporated into the poly（N-isopropylacrylamide）（PNIPAM）gel synthesis process to prepare a temperature-sensitive gel with high fluorescence intensity.In their release experiments,it was found that the release rate and total release of modified N-CQDs were lower than those before modification.This result was also observed in the heating experiments of the gels,and it was also found that heating did not cause their fluorescence to be quenched.After heating experiment,the fluorescence of the gel containing modified N-CQDs was better preserved,and the fluorescence of the gel containing N-CQDs was weakened.This indicated that the N-CQDs got double bonds by modification,which made it difficult to leak from the PNIPAM gel,and could be used for long-term monitoring.