Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature.
Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature.
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DOI：
10.1016/j.ijpharm.2014.01.007
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发表时间：
2014-04-10
影响因子：
5.8
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
--
作者：
Nahar, Kamrun;Absar, Shahriar;Patel, Brijeshkumar;Ahsan, Fakhrul
关键词：
在这项研究中，我们测试了磁性脂质体作为法舒地尔（一种治疗肺动脉高压（PAH）的研究药物）在肺内优先蓄积载体的可行性。为了开发最佳的可吸入制剂，制备了各种磁性脂质体，并对其理化性质、储存稳定性和体外释放特性进行了表征。使用荧光显微镜和HPLC评价了所选制剂被肺动脉平滑肌细胞（PASMC）-靶细胞-摄取的情况。在5-HT诱导的增殖的PASMCs中测试磁性脂质体在减少增生中的功效。在健康大鼠中监测经皮给药后的药物吸收曲线。优化的球形脂质体-平均尺寸为164 nm，zeta电位为-30 mV，包封率为85%-在120小时内显示出80%的累积药物释放。荧光显微镜研究显示，增强的脂质体的PASMCs下施加磁场的摄取：摄取是3倍，在没有磁场的情况下观察到的。在磁场的影响下，PASMC增殖减少了40%。优化的脂质体与PASMCs和支气管上皮细胞孵育时似乎是安全的。与普通法舒地尔相比，含法舒地尔的磁性脂质体的半衰期和曲线下面积分别延长了27倍和14倍。磁性脂质体可能是一种可行的传递系统，用于PAH的位点特异性治疗。
In this study, we tested the feasibility of magnetic liposomes as a carrier for pulmonary preferential accumulation of fasudil, an investigational drug for the treatment of pulmonary arterial hypertension (PAH). To develop an optimal inhalable formulation, various magnetic liposomes were prepared and characterized for physicochemical properties, storage stability and in vitro release profiles. Select formulations were evaluated for uptake by pulmonary arterial smooth muscle cells (PASMCs)–target cells–using fluorescence microscopy and HPLC. The efficacy of the magnetic liposomes in reducing hyperplasia was tested in 5-HT-induced proliferated PASMCs. The drug absorption profiles upon intratracheal administration were monitored in healthy rats. Optimized spherical liposomes–with mean size of 164 nm, zeta potential of −30 mV and entrapment efficiency of 85%–exhibited an 80% cumulative drug release over 120 hours. Fluorescence microscopic study revealed an enhanced uptake of liposomes by PASMCs under an applied magnetic field: the uptake was 3-fold greater compared with that observed in the absence of magnetic field. PASMC proliferation was reduced by 40% under the influence of the magnetic field. Optimized liposomes appeared to be safe when incubated with PASMCs and bronchial epithelial cells. Compared with plain fasudil, intratracheal magnetic liposomes containing fasudil extended the half-life and area under the curve by 27- and 14-fold, respectively. Magnetic-liposomes could be a viable delivery system for site-specific treatment of PAH.
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影响因子：
3.7
作者：
Absar, Shahriar;Nahar, Kamrun;Ahsan, Fakhrul
通讯作者：
Ahsan, Fakhrul
影响因子：
5.8
作者：
Ishida, T;Takanashi, Y;Kiwada, H
通讯作者：
Kiwada, H
影响因子：
5.8
作者：
Li, Fang;Sun, Jing;Shi, Donglu
通讯作者：
Shi, Donglu
影响因子：
14
作者：
Kim, Ji-Young;Kim, Jin-Ki;Kim, Chong-Kook
通讯作者：
Kim, Chong-Kook
DOI：
10.1016/j.jconrel.2013.01.011
发表时间：
2013-04-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Gupta V;Gupta N;Shaik IH;Mehvar R;McMurtry IF;Oka M;Nozik-Grayck E;Komatsu M;Ahsan F
通讯作者：
Ahsan F