Steric stabilization of RIPL peptide-conjugated liposomes and in vitro assessment
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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.
KeywordsSteric stabilization Liposome Docetaxel RIPL peptide Intracellular delivery Cytotoxicity
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2016R1A2B4011449).
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Conflict of interest
All authors (Moon Ho Jang, Chang Hyun Kim, Ho Yub Yoon, Si Woo Sung, Min Su Goh, Eun Seok Lee, Dong Jun Shin, and Young Wook Choi) declare that they have no conflict of interest.
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