Theoretical And Experimental Study On Photo-switching Smart Drug Delivery

In recent years,there has been an increasing interest in delivering small molecule drugs via smart drug carriers for temporal,spatial and dosage control of targeted therapy.Stimulus-responsive drug delivery systems with controlled release(CDR)and sustained release(SR)properties have been rapidly developed.Accurate delivery of therapeutic agents to the tumor region and effective preservation of normal tissue structures are important principles in the treatment of malignant lesions with extensive metastases or in close proximity to vital organs.However,currently available drug release techniques do not support precise drug release within a defined range of disease.We propose a personalized on-demand drug delivery strategy using photo-switching materials combined with engineering technology for automated and precise release of therapeutics.1.A photo-switching polymer containing spiropyran(SP)monomers is synthesized.We exploit the synergistic non-covalent interactions between the ring-opening merocyanine(MC)groups(i.e.,amphiphilic ionic interactions and π-π*stacking interactions)to simultaneously stabilize the microstructure of the polymer and reversibly switch the permeability of the membrane under alternating ultraviolet(UV)/visible(Vis)light irradiation.Meanwhile,anticancer drugs,such as adriamycin,have large π-bonds in their molecules,which can increase the stability between the photo-switching material and adriamycin and improve the drug loading.Moreover,the reversible nature of the photo-switching material can also logically control the drug permeation switching.In addition,under UV irradiation,the closed-loop SP is converted into MC and the permeability switch is opened;under Vis irradiation,the MC form can return to the SP form and the permeability switch is closed.Under alternating UV/Vis irradiation,the above permeability switch opening/closing process can be repeated without disintegration of the polymer structure.2.Theoretical models of photo-switching drug delivery systems with thin membranes,spheres and cylinders are developed.Mathematical physical modeling of drug delivery in photo-switching drug delivery systems is very useful.First of all,it allows us to gain a deeper understanding of the mechanisms controlling the release of drugs from specific types of dosage forms.Therefore,the safety of the respective treatment can be improved.Then,this allows to quantitatively predict the release and also to assess the influence of process parameters on the resulting drug release kinetics.Finally,theoretical models can help to determine the composition of the drug delivery system and the transport processes required to provide a specific,desired drug release profile.3.We present a photo-switching tailored graphical drug release strategy that utilizes photo-switching membranes in combination with tumor edge imaging to achieve personalized and automatically tailored drug release.Using UV or Vis light,the desired geometric pattern is projected onto the photo-switching membrane(PRM)to dynamically control the permeability and selective release of the PRM for treatment.The dynamic process of photo-switching drug passage through the PRM is modeled and compared with experimental results.This graphically tailored drug release strategy is validated in mimic experiments and its therapeutic efficacy is verified in human breast cancer cells.The technical potential of PRM for image-guided chemotherapy with precise control of drug release is demonstrated.4.We have developed a novel magnetic embolization microcapsule for transcatheter arterial chemoembolization(TACE)therapy.The pneumatic printing technique is used to encapsulate ferrosoferric oxide(Fe3O4)and drug in polylactic acid-glycolic acid copolymer(PLGA)to successfully prepare photo-switching microcapsules(PREMC)with stable structure,uniform particle size,recyclability,and photo-switching controlled release for on-demand drug delivery.The pneumatic printing technology can regulate the parameters as needed to prepare the desired PREMC-type bolus agent.In addition,theoretical models confirm that the theoretical profile can accurately predict the photo-switching drug release over time.The body-like fixation experiments confirm that PREMC can be released precisely in space.Finally,PREMC with precise drug release in time,space and dose is constructed.In vitro cellular studies show that PREMC can effectively inactivate tumor cells in the desired area by photo-switching for precision treatment.Ultimately,vascular mimetic experiments have shown that PREMC can achieve the integrated functions of embolization,degradation and drug delivery.Moreover,magnetic PREMC can be imaged by magnetic resonance imaging(MRI)after embolization,PREMC can be removed by magnetic field after embolization to inactivate tumor cells,and even PREMC that is not removed can be degraded.In addition,the method ensures delivery of high concentrations of chemotherapeutic agents to the tumor without increasing systemic concentrations and promotes tumor ischemia and necrosis.Finally,a type of embolic microcapsule with integrated features of simultaneous homogeneous,degradable,precise and controlled drug delivery and imaging capabilities has been successfully prepared,showing great potential for application in TACE.