Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs

Chen, Yongzhu; Tang, Cheng-Wei; Zhang, Jie; Gong, Meng; Su, Bo; Qiu, Feng

doi:10.2147/ijn.s71696

Cited by 19 publications

(9 citation statements)

References 43 publications

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“…DLS analysis in fact suggests the presence of at least two dimensions, one significantly below 100 nm (approximately 35-40 nm) and another from 200 nm to more than 1000 nm. This result can be explained by considering DDVVVVVV could form fibrillary supramolecular structures, as reported in the literature for similar amphiphilic peptides 20,21 . PEGylation has also been demonstrated as an effective approach to improve the stability and solubility of peptides in water.…”

Section: Resultssupporting

confidence: 74%

PEGylation affects the self-assembling behaviour of amphiphilic octapeptides

Perinelli

Campana

Singh

et al. 2019

International Journal of Pharmaceutics

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Surfactant-like peptides are a class of amphiphilic macromolecules, which are able to self-assemble in water forming different supramolecular structures. Among them, octapeptides composed of six hydrophobic and two hydrophilic residues have attracted interest since they have a length similar to those of natural phospholipids. Supramolecular structures of different amphiphilic octapeptides have been widely reported, but no study has been performed aimed at investigating the effect of PEGylation on their self-assembling behaviour. The aim of the present work was to synthesize and characterise the self-assembling behaviour of PEGylated alanine-or valine based amphiphilic octapeptides (mPEG1.9kDa-DDAAAAAA and mPEG1.9kDa-DDVVVVVV) in comparison to the non-PEGylated ones (DDAAAAAA and DDVVVVVV). The self-aggregation process in ultrapure water was investigated by fluorescence spectroscopy, small angle neutron scattering (SANS), dynamic light scattering (DLS), while the secondary structure was assessed by circular dichroism. PEGylation markedly affects the self-assembling behaviour of these amphiphilic octapeptides in terms of both critical aggregation concentration (CAC) and shape of the formed supramolecular aggregates. Indeed, PEGylation increases CAC and prevents the self-aggregation into fibrillary supramolecular aggregates (as observed for non-PEGylated peptides), by promoting the formation of micelle-like structures (as demonstrated for valine-based octapeptide). 2 On the other side, the secondary structure of peptides seems not to be affected by PEGylation. Overall, these results suggest that self-assembling behaviour of amphiphilic octapeptides can be modified by PEGylation, with a great potential impact for the future applications of these nanomaterials.

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Section: Resultssupporting

confidence: 74%

PEGylation affects the self-assembling behaviour of amphiphilic octapeptides

Perinelli

Campana

Singh

et al. 2019

International Journal of Pharmaceutics

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“…It would also pave the way towards use of this dye as a drug carrier, capable of targeted delivery of therapeutic compounds to areas where amyloid aggregates are found. This is enabled by noncovalent stabilization of supramolecular structures which provide a way to incorporate various external compounds via intercalation -a promising approach from the perspective of pharmacology (Jagusiak et al, 2018;Nummelin et al, 2017;Chen et al, 2015).…”

Section: Congo Redmentioning

confidence: 99%

Amyloids, Congo red and the apple-green effect

et al. 2019

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This paper attempts to find evidence of the previously proposed opinion that amyloids complex with Congo red molecules which preserve their supramolecular organization. As evidence of the overpowering tendency of Congo red molecules to self-assemble, we present an increasing acidity of molecules that follows increasing concentration of the dye, and a highly notable nonlinear increase in absorbance in the UV band (300–400 nm). This effect is analyzed in a model where the amyloid fibril is simulated by polyvinyl alcohol, providing a scaffold to stabilize a long Congo red micelle. Enormous absorbance in the UV band, coupled with the increasing association capabilities of individual Congo red molecules may cause the absorbance to extend even into the visible band. In addition, the UV and visual absorbance bands shift significantly, depending on conditions, and may either approach or recede from each other, leading to spectral changes which may be observed under polarized light. This commonly observed spectral variability appears to be associated with the strong capacity for electron delocalization in supramolecular Congo red complexed with amyloids.

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“…Although surfactant-like peptides (SLPs) forming nanovesicles or nanomicelles have been thought to be promising carriers for hydrophobic compounds, their drug-loading capacity was limited by a relatively small inner hydrophobic cavity. 4 , 5 In this regard microfluidic technologies were usually needed to manipulate the size of SLPs vesicles to improve their drug-loading capacity. 6 Mainly composed of highly hydrophobic amino acids (HAAs), SLPs also exhibited low water-solubility on their own, which may further limit the concentration of hydrophobic drugs they could reach.…”

Section: Introductionmentioning

confidence: 99%

High-Loading Self-Assembling Peptide Nanoparticles as a Lipid-Free Carrier for Hydrophobic General Anesthetics

Peng¹,

Kang²,

Gong³

et al. 2021

IJN

Self Cite

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Purpose Typical hydrophobic amino acids (HAAs) are important motifs for self-assembling peptides (SAPs), but they lead to low water-solubility or compact packing of peptides, limiting their capacity for encapsulating hydrophobic drugs. As an alternative, we designed a peptide GQY based on atypical HAAs, which could encapsulate hydrophobic drugs more efficiently. Although hydrophobic general anesthetics (GAs) have been formulated as lipid emulsions, their lipid-free formulations have been pursued because of some side effects inherent to lipids. Using GAs as targets, potential application of GQY as a carrier for hydrophobic drugs was evaluated. Methods Thioflavin-T (ThT) binding test, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to examine the self-assembling ability of GQY. Pyrene and 8-Anilino-1-naphthalenesulfonic acid (ANS) were used to confirm formation of hydrophobic domain in GQY nanoparticles. Using pyrene as a model, GQY’s capacity to encapsulate hydrophobic drugs was evaluated. GAs including propofol, etomidate and ET26 were encapsulated by GQY. Loss of righting reflex (LORR) test was conducted to assess the anesthetic efficacy of these lipid-free formulations. Paw-licking test was used to evaluate pain-on-injection of propofol-GQY (PROP-GQY) formulation. Hemolytic and cytotoxicity assay were used to evaluate biocompatibility of GQY. Results Stable nanoparticles containing plenty of hydrophobic cavities could be formed by GQY, which could encapsulate hydrophobic drugs at very high concentration and form stable suspensions. Propofol, etomidate and ET26 formulated by GQY showed anesthetic efficacy comparable to their currently available formulations. Unlike clinic lipid emulsion, PROP-GQY formulation did not cause pain-on-injection in rats. Neither obvious cytotoxicity nor hemolytic activity of GQY was observed. Conclusion GQY could encapsulate GAs to obtain stable and effective formulations. As a lipid-free carrier, GQY exhibited considerable biocompatibility and other side benefits such as reducing pain-on-injection. More SAPs based on atypical HAAs could be designed as promising carriers for hydrophobic drugs.

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Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs

Cited by 19 publications

References 43 publications

PEGylation affects the self-assembling behaviour of amphiphilic octapeptides

PEGylation affects the self-assembling behaviour of amphiphilic octapeptides

Amyloids, Congo red and the apple-green effect

High-Loading Self-Assembling Peptide Nanoparticles as a Lipid-Free Carrier for Hydrophobic General Anesthetics

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