Microfluidic synthesis of PEG- and folate-conjugated liposomes for one-step formation of targeted stealth nanocarriers.
Microfluidic synthesis of PEG- and folate-conjugated liposomes for one-step formation of targeted stealth nanocarriers.
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DOI：
10.1007/s11095-013-0998-3
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发表时间：
2013-06
影响因子：
3.7
通讯作者：
DeVoe, Don L.
中科院分区：
文献类型：
--
作者：
Hood, Renee R.;Shao, Chenren;Omiatek, Donna M.;Vreeland, Wyatt N.;DeVoe, Don L.
研究了一种微流控流体动力聚焦技术，用于连续流合成聚乙二醇改性和聚乙二醇叶酸功能化的脂质体，用于靶向给药。在热塑性微流控装置中的可控层流促进了脂质体从初始的脂类组成中自组装，包括含有聚乙二醇脂和叶酸-聚乙二醇脂结合物的脂类/胆固醇混合物。考察了流动条件、脂类成分和脂质体大小之间的关系，并通过UV-Vis吸光度测量和脂质体Zeta电位表征确定了这些参数对聚乙二醇乙二醇酯和叶酸掺入的影响。在所研究的各种脂质体尺寸范围内，聚乙二醇酯和叶酸均成功地掺入到微流控合成的脂质体中。聚乙二醇脂质体的掺入效率与脂质体直径呈负相关。在不同流动条件下，叶酸-脂质也能有效地整合到脂质体中。利用微流控聚焦平台成功地合成了相对较大的聚乙二醇改性和叶酸-聚乙二醇改性脂质体，为功能化脂质体的制备提供了一种简单、低成本、快速的方法。阐明了制备条件与聚乙二醇或叶酸-聚乙二醇功能化之间的关系，为微流控方法的优化提供了洞察过程和确定了形成用于药物应用的功能化脂质体的途径。
A microfluidic hydrodynamic flow focusing technique enabling the formation of small and nearly monodisperse liposomes is investigated for continuous-flow synthesis of poly(ethylene glycol) (PEG)-modified and PEG-folate-functionalized liposomes for targeted drug delivery. Controlled laminar flow in thermoplastic microfluidic devices facilitated liposome self-assembly from initial lipid compositions including lipid/cholesterol mixtures containing PEG-lipid and folate-PEG-lipid conjugates. The relationships between flow conditions, lipid composition, and liposome size were evaluated, and the impact of these parameters on PEG and folate incorporation were determined through a combination of UV-vis absorbance measurements and characterization of liposome zeta potential. Both PEG and folate were successfully incorporated into microfluidic-synthesized liposomes over the full range of liposome sizes studied. The efficiency of PEG-lipid incorporation was found to be inversely correlated with liposome diameter. Folate-lipid was also effectively integrated into liposomes at various flow conditions. Liposomes incorporating relatively large PEG-modified and folate-PEG-modified lipids were successfully synthesized using the microfluidic flow focusing platform, providing a simple, low cost, rapid method for preparing functionalized liposomes. Relationships between preparation conditions and PEG or folate-PEG functionalization have been elucidated, providing insight into the process and defining paths for optimization of the microfluidic method toward the formation of functionalized liposomes for pharmaceutical applications.
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影响因子：
15
作者：
Jahn, A;Vreeland, WN;Locascio, LE
通讯作者：
Locascio, LE
影响因子：
3.9
作者：
Jahn, Andreas;Vreeland, Wyatt N.;Gaitan, Michael
通讯作者：
Gaitan, Michael
影响因子：
3.9
作者：
Ramachandran, Srinivasan;Quist, Arjan P.;Lal, Ratnesh
通讯作者：
Lal, Ratnesh
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
影响因子：
3.4
作者：
LITZINGER, DC;BUITING, AMJ;HUANG, L
通讯作者：
HUANG, L