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KMID : 1146920190490010115
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Journal of Pharmaceutical Investigation
2019 Volume.49 No. 1 p.115 ~ p.125
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Steric stabilization of RIPL peptide-conjugated liposomes and in vitro assessment
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Jang Moon-Ho
Kim Chang-Hyun
Yoon Ho-Yub
Sung Si-Woo
Goh Min-Su
Lee Eun-Seok
Shin Dong-Jun
Choi Young-Wook
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Abstract
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RIPL peptide-conjugated liposomes (PEG-RIPL-Ls) were sterically stabilized with polyethylene glycol (PEG) to prevent recognition by the mononuclear phagocytic system (MPS) and prolong their systemic circulation in vivo. PEG-modified maleimide-derivatized liposomes were prepared by a thin-film hydration method and RIPL peptide was conjugated via a thiol-maleimide reaction. To optimize the system, different chain lengths of PEG were used to prepare PEG-RIPL-L. PEG-RIPL-Ls were positively charged nanodispersions and docetaxel (DTX) was successfully encapsulated by pre-loading with an encapsulation efficiency and drug loading capacity of 31?35% and 15?20 μg/mg, respectively. DTX release showed a biphasic pattern, with rapid release in the initial period of 6 h, followed by sustained release for up to 72 h. Additionally, 5 mol% PEG3000-grafted RIPL-L (PEG3K-RIPL-L) showed enhanced anti-adsorption compared to 5 mol% PEG2000-grafted RIPL-L (PEG2K-RIPL-L). Confocal microscopy and flow cytometry using a fluorescence probe (FITC-dextran) demonstrated the greatest stealth effect of PEG3K-RIPL-L. Further analysis of cellular uptake showed that PEG3K-RIPL-L maintained target-selective intracellular delivery capacity. Cytotoxicity analysis demonstrated that PEG3K-RIPL-L had a 1.8-fold lower IC50 value than DTX-Sol. Steric stabilization of RIPL-L was successfully achieved by surface modification with PEG3K, and thus PEG3K-RIPL-L shows potential as a nanocarrier for targeted drug delivery in blood circulation.
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KEYWORD
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Steric stabilization, Liposome, Docetaxel, RIPL peptide, Intracellular delivery, Cytotoxicity
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