A coupled bimodal SPECT-CT imaging and brain kinetics studies of zolmitriptan-encapsulated nanostructured polymeric...

The present investigation deals with preparation and characterization of anti-migraine zolmitriptan (ZMT) nanostructured polymeric carriers for nose to brain drug targeting. The drug-loaded colloidal nanocarriers of ZMT were prepared by modified ionic gelation of cationic chitosan with anionic sodium tripolyphosphate and characterized for particle size, zeta potential, and entrapment efficiency. Further, in order to investigate nose to brain drug targeting, biodistribution, and brain kinetics studies were performed using ^99mtechnetium radiolabeled nanocarriers (^99mTc-ZMTNP) in Swiss albino mice. The results were compared with intranasal pure drug solution (^99mTc-ZMT) and intravenous nanocarriers (^99mTc-ZMTNP). A single photon emission computerized tomography (SPECT) radioimaging studies were also carried out to visualize and confirm brain uptake of nanocarriers. The optimized nanocarriers showed particle size of 161 nm, entrapment efficiency of 80.6%, and zeta potential of + 23.7 mV. The pharmacokinetic parameters, C_max, and AUC_0-∞ values for ZMT concentration in the brain expressed as percent radioactivity per gram of brain in intranasal and intravenous route of administration were calculated. The brain C_max and AUC_0-∞ values found in three groups, intranasal ^99mTc-ZMTNP, intranasal ^99mTc-ZMT, and intravenous ^99mTc-ZMTNP were (0.427 and 1.889), (0.272 and 0.7157), and (0.204 and 0.9333), respectively. The higher C_max values of intranasal ^99mTc-ZMTNP suggests better brain uptake as compared to other routes of administration. The significant higher values of nose to brain targeting parameters namely, drug targeting index (5.57), drug targeting efficiency (557.08%), and nose to brain drug direct transport (82.05%) confirmed drug targeting to brain via nasal route. The coupled bimodal SPECT-CT scintigrams confirm the brain uptake of intranasal ^99mTc-ZMTNP demonstrating major radioactivity accumulation in brain. This study conclusively demonstrated the greater uptake of ZMT-loaded nanocarriers by nose to brain drug targeting, which proves promising drug delivery system.