Charged polypeptide vesicles with controllable diameter
ABSTRACT We report the preparation and characterization of charged, amphiphilic block copolypeptides that form stable vesicles and micelles in aqueous solution. Specifically, we prepared and studied the aqueous self-assembly of a series of poly(L-lysine)-b-poly(L-leucine) block copolypeptides, KxLy, where x ranged from 20 to 80 and y ranged from 10 to 30 residues, as well as the poly(L-glutamatic acid)-b-poly(L-leucine) block copolypeptide, E60L20. Furthermore, the vesicular assemblies show dynamic properties, indicating a high degree of membrane fluidity. This characteristic provides stimuli-responsive properties to the vesicles and allows fine adjustment of vesicle size using liposome-based extrusion techniques. Vesicle extrusion also provides a straightforward means to trap solutes, making the vesicles promising biomimetic encapsulants.
SourceAvailable from: Dipti Kakkar[Show abstract] [Hide abstract]
ABSTRACT: Huisgen's 1,3-dipolar cycloaddition (“Click Chemestry”) has been used to prepare amphiphilic PEO-b-PBLG diblock and PBLG-b-PEO-b-PBLG triblock copolymers as potential carriers of anticancer drugs. Spherical and flower shaped micelles (D ≈100 nm) were obtained from diblock and triblock copolymers respectively. DOX was effectively encapsulated up to 18 wt.% and 50–60% of it was steadily released from the micelles over a period of 7 d. Flow cytometry and fluorescence microscopy confirmed the effective intracellular uptake as well as the sustained release of DOX from micelles. These results suggest that the diblock as well as triblock copolymers are promising carriers for intra-cellular drug delivery.Macromolecular Bioscience 12/2014; 15(1). DOI:10.1002/mabi.201400451 · 3.65 Impact Factor
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ABSTRACT: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(l-phenylalanine)-b-poly(l-serine) (PFS) polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(l-serine) was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110-240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to α-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 μg mL(-1) were stable in pH 5-9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played a positive role in the internalization of PFS. The more interesting thing was that the uptake inhibition impacted on normal cells but not on tumor cells at the physiological concentration of serine. The difference in the uptake of PFS micelles was fourfold as high between the tumor cells and the normal cells, which indicated that PFS micelles had good tumor targeting in vitro. In conclusion, PFS micelles reported in this work were a promising drug delivery system for tumor targeting therapy.International Journal of Nanomedicine 01/2014; 9:5849-5862. DOI:10.2147/IJN.S73111 · 4.20 Impact Factor
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ABSTRACT: In this work, the influence of the ionic strength and phosphate ions on poly(L-lysine) hydrodynamic radius, conformation and persistence lengths has been studied for molar masses comprised between 3000 and 70 000 g/mol. Mark-Houwink coefficients have been obtained via the determination of poly(L-lysine) hydrodynamic radius using Taylor dispersion analysis. The influence of phosphate ions and ionic strength on the solvent quality (poor, 0, or good solvent) for poly(L-lysine) have been studied in details. Quantitative data on hydrodynamic radius, persistence length, Mark-Houwink coefficients are provided at pH 7.4, in the range of 10 mM to 1 M ionic strength, and for different phosphate ion concentrations from 0.1 mM to 50 mM under physiological conditions (154 mM ionic strength, pH 7.4). The strong influence of phosphate ions on poly(L-lysine) properties was finally illustrated by studying the interactions (stoichiometry, binding constant, and cooperativity) between poly(L-lysine) of DP 50 and human serum albumin, in the absence and in the presence of phosphate ions at pH 7.4.Macromolecules 08/2014; 47(15):5320-5327. DOI:10.1021/ma501058v · 5.93 Impact Factor