Title: Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery

Abstract

Peptoids are highly biocompatible pseudopeptidic polyglycines with designable substituents on the nitrogen atoms. The therapeutic and drug-carrying potential of these materials requires a fundamental understanding of their interactions with lipid bilayers. Here, we use amphiphilic polypeptoids with up to 100 monomeric units where a significant fraction (26%) of the nitrogen atoms are functionalized with decyl groups (hydrophobes) that insert into the lipid bilayer through the hydrophobic effect. These hydrophobically modified polypeptoids (HMPs) insert their hydrophobes into lipid bilayers creating instabilities that lead to the rupture of vesicles. At low HMP concentrations, such rupture leads to the creation of large fragments which remarkably anchor to intact vesicles through the hydrophobic effect. At high HMP concentrations, all vesicles rupture to smaller HMP–lipid fragments of the order of 10 nm. We show that the technique for such nanoscale polymer–lipid fragments can be exploited to sustain highly hydrophobic drug species in solution. Using the kinase inhibitor, Sorafenib as a model drug, it is shown that HMP–lipid fragments containing the drug can efficiently enter a hepatocellular carcinoma cell line (Huh 7.5), indicating the use of such fragments as drug delivery nanocarriers.

Authors:

Zhang, Yueheng ^[1]; Heidari, Zahra ^[1]; Su, Yang ^[1]; Yu, Tianyi ^[2]; Xuan, Sunting ^[2]; Omarova, Marzhana ^[1]; Aydin, Yucel ^[1]; Dash, Srikanta ^[1]; Zhang, Donghui  ^[2];

• Search DOE PAGES for author "Zhang, Donghui"
• Search DOE PAGES for ORCID "0000-0003-0779-6438"

John, Vijay  ^[1]

• Search DOE PAGES for author "John, Vijay"
• Search DOE PAGES for ORCID "0000-0001-5426-7585"

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+ Show Author Affiliations

1. Tulane University, New Orleans, LA (United States)
2. Louisiana State University, Baton Rouge, LA (United States)

Publication Date:

Tue Nov 05 00:00:00 EST 2019

Research Org.:

Louisiana State Univ., Baton Rouge, LA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)

OSTI Identifier:

1672152

Alternate Identifier(s):

OSTI ID: 1615947

Grant/Contract Number:  

SC0012432; 1805608

Resource Type:

Accepted Manuscript

Journal Name:

Langmuir

Additional Journal Information:

Journal Volume: 35; Journal Issue: 47; Journal ID: ISSN 0743-7463

Publisher:

American Chemical Society

Country of Publication:

United States

Language:

English

Subject:

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; Vesicles; Thin films; Lipids; Hydrophobicity; Hydration