Study On The Stability Of Polymer Micelles In Simulated Microenvironment

Polymeric micelles are widely used as drug carrier systems.Current studies have shown that polymer micelles were quickly dissociated after injection into the patient body,which leads to the prerelease of drugs and reduces targeting efficiency and bioavailability of drug delivery system.Therefore,it is essential to study the in-vivo dissociation of polymeric micelles.Due to the complexity of the in-vivo environment,such as microvascular vessels,it is difficult to directly investigate the dissociation of polymeric micelles,therefore the principle of micellar dissociation is still not clear.It is desirable to build an in-vitro model that simulates the microvascular structures and hemodynamics for exploring the dissociation of polymer micelles.In recent years,microfluidics has been emerging as an ideal platformto mimic microvascular vessels,due to its microdimensionality and facile manipulation of fluids.In the present study,we designed and fabricated a microfluidic model mimiking the in-vivo microvacular vessel.The microfluidic system provides a physical microenvironment for studying the dissociation behavior of polymer micelles in vitro,where the disassociation of polymeric micelles is indicated by fluorescence resonance energy transfer(FRET)signal.The dissociation behavior of the micelles in the simulated microenvironment can be monitored in real time according to the change of the FRET intensity.The dissociation kinetic transformation process of the nanometer micelles can be clarified,which is the foundation for further research that development of highly efficient and stable nanomedicine.In this paper,the polyethylene glycol poly lactone,polyethylene glycol polylactic acid and polyethylene glycol polystyrene block copolymers were successfully synthesized.Then the hydrophobic ends of the three polymers were modified with fluorescent dyes Cy5 and Cy5.5respectively,a polymer micelle with fluorescence resonance energy transfer effect(FRET)was prepared,and the dissociation of micelles was characterized by establishing a linear relationship between FRET signal and its dissociation.And the micro-vessel model was successfully constructed on the microfluidic chip to study the polymer micelles.Studies have shown that polymer micelles were not dissociated merely bymicrofluidic chips generated shear stress nor blood components under static environment.The dissociation of polymer micelles is the result of the combination of shear stress and blood components.Blood components including serum,plasma,protein and fresh blood exhibited varying impacts on the stability of polymer micelles under shear stress.Stability of micelle under blood shear strength is related to the hydrophobic section of the copolymer.The higher the glass transition temperature of the hydrophobic section,the more stable are the polymeric micelle.