The consideration of indolicidin modification to balance its hemocompatibility and delivery efficiency

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題名:	The consideration of indolicidin modification to balance its hemocompatibility and delivery efficiency
作者:	金秀蓮;Tsai, Ching-Wei;Hu, Wei-Wen;Liu, Chih-I;Ruaan, Ruoh-Chyu;Tsai, Bing-Chang;Jin, Shiow-Lian Catherine;Chang, Yung;Chen, Wen-Yih
貢獻者:	生醫理工學院生命科學系
關鍵詞:	Animals;Antimicrobial Cationic Peptides - administration & dosage;Antimicrobial Cationic Peptides - chemistry;Antimicrobial Cationic Peptides - pharmacokinetics;Antimicrobial Cationic Peptides - pharmacology;Cell Survival - drug effects;Cell-penetrating peptide;Direct penetration;Drug Delivery Systems - methods;Drug Liberation;Fluorescein-5-isothiocyanate - chemistry;Fluorescein-5-isothiocyanate - pharmacokinetics;Hemolysis - drug effects;Hydrophobic and Hydrophilic Interactions;Hydrophobicity;Indolicidin;Mice;NIH 3T3 Cells;Peptides - chemical synthesis;Peptides - pharmacokinetics;Peptides - pharmacology;Transmembrane mechanism
日期:	2015-10-15
上傳時間:	2026-04-23 11:14:00 (UTC+8)
出版者:	Netherlands: Elsevier B.V
摘要:	摘要： [Display omitted] Indolicidin (IL) is an antimicrobial peptide (AMP), which has been utilized as a cell penetrating peptide (CPP) for drug delivery. However, the hemolysis restricts its clinical application. Therefore, we investigated the delivery efficiency and hemocompatibility of IL and its derivatives. The transportation of fluorophore to NIH/3T3 cells could be improved either by in accompany with these peptides or in the form of peptide-conjugates. The hydrophobicity scales of these peptides were calculated according to their residues, which were compared to their effects on hemolysis as well as cell uptake efficiency. The results suggested that the cell penetrability of IL and its derivatives was related to their hydrophobicity scales based on the octanol-interface scale (ΔGoct-if), whereas their hemolysis levels depended on the hydrophobicity scales based on interface (ΔGwif). Consequently, we designed two peptides, IL-R57F89 and SAP10, to validate the correlation. These two peptides had similar ΔGwif; however, the ΔGoct-if of SAP10 was much higher than that of IL-K7F89. Both IL-R57F89 and SAP10 demonstrated extremely low hemolysis. Compared to the limit cell uptake of SAP10, IL-R57F89 greatly promoted the delivery efficiency. These results were consistent to our prediction, suggesting that hydrophobicity scales should be a useful preliminary guidance for AMP-derived CPP design. 其他題名： Int J Pharm 出版者： Netherlands: Elsevier B.V 出版日期： 2015-10-15 出處： International journal of pharmaceutics, 2015-10, Vol.494 (1), p.498-505 版權： 2015 Elsevier B.V. 版權： Copyright © 2015 Elsevier B.V. All rights reserved. 識別號： ISSN: 0378-5173 識別號： ISSN: 1873-3476 識別號： EISSN: 1873-3476 識別號： DOI: 10.1016/j.ijpharm.2015.08.037 識別號： PMID: 26291880
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