Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune, Maharashtra, India.
Department of Pharmaceutics, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
Drug Deliv Transl Res. 2018 Jun;8(3):797-805. doi: 10.1007/s13346-017-0474-4.
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 technetium radiolabeled nanocarriers (Tc-ZMTNP) in Swiss albino mice. The results were compared with intranasal pure drug solution (Tc-ZMT) and intravenous nanocarriers (Tc-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, and AUC 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 and AUC values found in three groups, intranasal Tc-ZMTNP, intranasal Tc-ZMT, and intravenous Tc-ZMTNP were (0.427 and 1.889), (0.272 and 0.7157), and (0.204 and 0.9333), respectively. The higher C values of intranasal Tc-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 Tc-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.
本研究致力于制备和表征抗偏头痛佐米曲普坦（ZMT）纳米结构聚合物载体，用于鼻内递药至脑。通过阳离子壳聚糖与阴离子三聚磷酸钠的离子凝胶化改性制备载药胶体纳米载体，并对其粒径、Zeta 电位和包封效率进行了表征。此外，为了研究鼻内递药至脑的靶向性，采用锝标记纳米载体（Tc-ZMTNP）在瑞士白化小鼠体内进行了生物分布和脑内药动学研究，并与鼻内纯药物溶液（Tc-ZMT）和静脉内纳米载体（Tc-ZMTNP）进行了比较。还进行了单光子发射计算机断层扫描（SPECT）放射成像研究，以可视化和确认纳米载体的脑摄取。优化后的纳米载体粒径为 161nm，包封效率为 80.6%，Zeta 电位为+23.7mV。通过计算 ZMT 浓度的药动学参数 C 和 AUC 值（表示为脑内每克脑的放射性百分比），计算出经鼻内和静脉途径给予 ZMT 后，脑内的 ZMT 浓度。三组的脑 C 和 AUC 值分别为：经鼻内 Tc-ZMTNP、经鼻内 Tc-ZMT 和经静脉 Tc-ZMTNP 分别为（0.427 和 1.889）、（0.272 和 0.7157）和（0.204 和 0.9333）。与其他给药途径相比，经鼻内 Tc-ZMTNP 的脑 C 值更高，表明脑摄取更好。药物靶向参数（药物靶向指数 5.57、药物靶向效率 557.08%和鼻内至脑直接药物输送 82.05%）的显著较高值证实了经鼻途径的药物靶向至脑。SPECT-CT 闪烁扫描图联合证实了经鼻 Tc-ZMTNP 的脑摄取，显示大脑中主要放射性物质的积累。本研究结论表明，通过鼻内递药至脑的方式，载药纳米载体的摄取量更大，这证明了其是一种有前途的药物传递系统。
