System Design And Synthesis, Based On The Optical Trigger Type Of Light-control Drug Release

Recently, with the continuous development of biomedical material science, new drug release system, especially for controlled drug release system, has become one of the most important tasks in the studies of pharmaceutical area. These "smart" drug release systems can realize the targeted drug release, which helps to improve drug efficacy, reduce side effects of drugs, and has attractive applications in disease treatment and health care. Generally, controlled drug release can be achieved in two strategies:internal and external stimulations. Comparing with the internal stimulations, the external stimulations often control the drug release more accurately. Among these, the design and synthesis of photocontrolled drug release system has attracted great interest, since light can provide the highly accurate external stimulation with non-physical contact at any desired times and sites. At present, the study for the photo-controlled drug delivery systems is still concentrated on the fundamental reaearch area, and there are many problems including the following two aspects:(1) How to extend the irritation wavelength of photorelease and reduce the requirement for the light source. These are the main problem for the presented chemical photo-controlled drug release system. By far, one significant limitation of the aforementioned photo-controllable drug release system is the use of cytotoxic UV light. To avoid using UV light, one effort is to design new phototriggers that can absorb at longer wavelengths, however this approach encounters difficulty of synthesizing; another approach is to utilize two-photon excitation, however it is expensive due to the need of an fs-mode laser. For aforementioned problems, the first part of our work is to demonstrate a new anticancer drug release system under the irradiation of visible light based on photo-induced electron transfer. In this system, water soluble QDs and L-cysteine were used as the photosensitizer and electron donor, NAP ester linked with an anticancer drug 5-fluorouracil acid (5-FUA) as an electron acceptor to generate photo-controlled release. Upon the irradiation of light, the photosensitizer QDs adsorbed the light, and then the sensitized QDs transferred an electron to NAP ester which induced the cleavage of the 5-FUA. The donor in the system then supplied an electron to QDs which promoted the progress of cleavage. The allowance of the light absorption step decoupling from the drug release provided the opportunity to tune the properties of QDs to optimize the release, thus permitting more control over the wavelengths of light used in the release process. Finally, the HPLC and fluorescent analysis for the photolysis process proved that the drug can be released effectively. We envision that this novel method has the potential to fulfill an increasing need for versatile and controllable drug delivery systems.(2) How to solve the problem for the difficulty of drug conjugated with the phototriggers. To our knowledge, the drug is always chemical conjugated to the phototriggers in most phototrigger-contained photo-controlled drug release systems. While, for most drug molecules, it is hard to achieve since there are no enough active groups, which induced the difficulty for conjugation and limitation of selected drugs. In order to solve this problem, in the second part of our paper, we put forward to use coumarin phototrigger to link cyclodextrins (CD) in a polymer system, in which hydrophobic drugs are enwrapped in the cavity of CD by supramolecular assembly. Upon the irradiation of light, the cyclodextrins (CD) containing drug molecules are released, and the drug molecules are released afterward when CD is enzymatic hydrolyzed by amylase. In this system, the drug is linked to the phototrigger through cyclodextrins indirectly, not the chemical bond directly. This strategy can avoid the difficulty of organic synthesis and highly enrich the drug types in the photocontrolled drug release system. In our work, we have not gotten the ideal result, because the photolysis efficiency of the 7-hydroxy-coumarin we used in this system is very lower. In our future work, we will try to further modify coumarin phototrigger to improve this system. After all, this new system also supplies a newly method and trial for the future research of photo-controlled drug release system.