One Step Encapsulation of Small Molecule Drugs in Liposomes via Electrospray-Remote Loading.
One Step Encapsulation of Small Molecule Drugs in Liposomes via Electrospray-Remote Loading.
复制标题
DOI：
10.1021/acs.molpharmaceut.5b00528
复制
发表时间：
2016-01-04
影响因子：
4.9
通讯作者：
Ainslie KM
中科院分区：
文献类型：
--
作者：
Duong AD;Collier MA;Bachelder EM;Wyslouzil BE;Ainslie KM
瑞喹莫特是一种Toll样受体（TLR）7/8激动剂，以前曾被用作疫苗佐剂、病毒性病变和皮肤癌的局部治疗以及抗病毒治疗。我们报告了远程装载和电喷雾的组合应用，以生产脂质体瑞喹莫特，更广泛的目标是提高药物包封效率和脂质体生产方法的可扩展性。当使用远程装载时，脂质体中的药物装载从小于1%增加到大于3%质量，无论脂质体是通过薄膜水合还是电喷雾方法产生。动态光散射（DLS）测定薄膜和电喷雾方法的平均囊泡直径分别为137 ± 11 nm和103 ± 4 nm。透射电子显微镜（TEM）图像显示球形囊泡的大小与DLS测量一致。体外药物释放曲线发现，在pH 5.5和7.4下，大部分药物保留在脂质体内。当RAW巨噬细胞暴露于药物时，亚硝酸盐产生的增加也证明了脂质体药物的体外生物活性。我们的研究结果表明，通过可扩展的电喷雾方法形成的远程加载的脂质体具有与通过传统的批量方法产生的脂质体相当的特性。这里讨论的方法不限于瑞喹莫特的增强递送。相反，它们应该容易地适应于与远程加载相容的其他化合物。
Resiquimod is a Toll-like receptor (TLR) 7/8 agonist that has previously been used as a vaccine adjuvant, as a topical treatment of viral lesions and skin cancer, and as an antiviral treatment. We report on the combined application of remote loading and electrospray to produce liposomal resiquimod, with the broader goals of improving drug encapsulation efficiency and scalability of liposome production methods. Drug loading in liposomes increased from less than 1% to greater that 3% by mass when remote loading was used, whether the liposomes were generated by thin-film hydration or electrospray methods. Dynamic light scattering (DLS) determined mean vesicle diameters of 137 ± 11 nm and 103 ± 4 for the thin-film and electrospray methods, respectively. Transmission electron microscopy (TEM) images showed spherical vesicles with sizes consistent with the DLS measurements. In vitro drug release profiles found that most of the drug remained within the liposomes at both pH 5.5 and 7.4. The in vitro bioactivity of the liposomal drug was also demonstrated by the increase in nitrite production when RAW macrophages were exposed to the drug. Our findings indicate that the remotely loaded liposomes formed via the scalable electrospray method have characteristics comparable to those produced via conventional batch methods. The methods discussed here are not limited to the enhanced delivery of resiquimod. Rather, they should be readily adaptable to other compounds compatible with remote loading.
登录
查看更多内容
DOI：
10.1016/j.jconrel.2008.10.011
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Jhunjhunwala S;Raimondi G;Thomson AW;Little SR
通讯作者：
Little SR
影响因子：
3.5
作者：
BARENHOLZT, Y;AMSELEM, S;LICHTENBERG, D
通讯作者：
LICHTENBERG, D
DOI：
10.1073/pnas.77.7.4030
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HWANG, KJ;LUK, KFS;BEAUMIER, PL
通讯作者：
BEAUMIER, PL
影响因子：
4.9
作者：
Bachelder EM;Beaudette TT;Broaders KE;Fréchet JM;Albrecht MT;Mateczun AJ;Ainslie KM;Pesce JT;Keane-Myers AM
通讯作者：
Keane-Myers AM
影响因子：
3.3
作者：
Justo, OR;Moraes, AM
通讯作者：
Moraes, AM