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Design and Evaluation of Peptide Amphiphiles with Different Hydrophobic Blocks for Simultaneous Delivery of Drugs and Genes
Author(s) -
Wiradharma Nikken,
Tong Yen Wah,
Yang YiYan
Publication year - 2010
Publication title -
macromolecular rapid communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 154
eISSN - 1521-3927
pISSN - 1022-1336
DOI - 10.1002/marc.200900935
Subject(s) - peptide , amphiphile , micelle , nanoparticle , gene delivery , oligopeptide , chemistry , materials science , transfection , nuclear chemistry , stereochemistry , nanotechnology , aqueous solution , organic chemistry , polymer , gene , biochemistry , copolymer
In this study, peptides with six different compositions were designed and synthesized to study the effect of the structure of the hydrophobic block in triblock oligopeptide amphiphiles ((A m X) n H 5 K 15 ) on self‐assembly properties, drug loading capacity and gene expression efficiency. The peptides were synthesized using a standard Fmoc‐solid phase peptide synthesis protocol, which are A 12 H 5 K 15 , A 11 FH 5 K 15 , (A 5 F) 2 H 5 K 15 , (A 3 F) 3 H 5 K 15 , (AF) 6 H 5 K 15 and (AL) 6 H 5 K 15 . A 12 H 5 K 15 , A 11 FH 5 K 15 , (A 5 F) 2 H 5 K 15 and (A 3 F) 3 H 5 K 15 , formed micelles at concentrations above 200 mg · L −1 with large size or aggregation. However, (AF) 6 H 5 K 15 and (AL) 6 H 5 K 15 had CMC values of 42 and 49 mg · L −1 respectively, and the resulting micelles were much smaller in size as compared to the other peptide designs (108 and 233 nm for (AF) 6 H 5 K 15 and (AL) 6 H 5 K 15 , respectively). In addition, both peptides were able to load paclitaxel (PTX) into nanoparticles although PTX‐loaded (AF) 6 H 5 K 15 nanoparticles had a smaller size (278 versus 295 nm, respectively). Encapsulation efficiency of PTX with (AF) 6 H 5 K 15 nanoparticles was 74%. Gene transfection studies showed that luciferase expression level induced by (AF) 6 H 5 K 15 micelles in HepG2 cell line was much higher than that mediated by (AL) 6 H 5 K 15 micelles at their respective optimal N/P ratios (3.2 × 10 8 versus 3.9 × 10 7 RLU · mg proteins −1 ). Therefore, simultaneous delivery of PTX and luciferase‐encoding plasmid was conducted using (AF) 6 H 5 K 15 micelles against HepG2 cells, and the results demonstrated that the co‐delivery of PTX at 0.01 mg · L −1 further increased luciferase expression level from 3.2 × 10 8 to 8.0 × 10 8 RLU · mg proteins −1 at the optimal N/P ratio (i.e., 18). In summary, it is important to optimize the hydrophobic block of the oligopeptide amphiphiles in order to achieve desired properties for co‐delivery of drugs and genes.