Fluorescence-based Online Analysis Of Doxorubicin Drug Concentration In Microfluidic Systems

In the present work,an offline detection method of hydrochloric acid doxorubicin was firstly established. Further a fluorescence-based online analysis method was developed for doxorubicin hydrochloride and the drug-loaded microspheres. Those methods were then applied for online detection of doxorubicin concentration during the process of drug release form drug-loaded microspheres.The offline fluorescence analysis method of doxorubicin hydrochloride was established by using spectrophotometer. By using that method it was measured that doxorubicin hydrochloride displayed a maximum excitation wavelength at λex= 469 nm and a maximum emission wavelength at λem= 593 nm. The fluorescence intensity and concentration fit into a good linear relationship in the concentrastion range of 9.90×10-8mol/L ~ 1.97×10-5mol/L, with a linear coefficient of 0.9945 and a recovery rate of 98.99%. The drug concentration of doxorubicin hydrochloride injection was measured to be 12.24%, with a recovery rate of standard addition of 101.96%, and a good reperatability. By using that method DC bead microspheres were studied with different size ranges including 350 μm ~ 550 μm, 200 μm ~ 400 μm and 75 μm ~ 175 μm. It was found that to load a given amount of drug(75 mg) it need different time periods of 120 min, 90 min and 60 min, respectively. The envelopment rate of microspheres was 98.8% and the loading dosage mass was 48.9%.Basis on offline fluorescence analysis, the fluorescence microscope coupled with a high resolution imaging system was used together with a MATLAB image analysis program as an online analytical method for hydrochloric acid doxorubicin measurement. By using this method the drug elution process was measured for350 μm ~ 550 μm microspheres with hydrochloric acid doxorubicin within a micro channel(width = 500μm). The fluid flow rates were controlled at 4 min/m L,7 min/m L, 9 min/m L, and 13 min/m L to determine the highest durg elution rate form durg-loadde microspheres. The experimental results showed that the method developed can further applied to study pharmacokinetics for controlled drug release form drug-loaded microspheres.