Arginine-based cationic surfactants: Biodegradable auxiliary agents for the formation of hydrophobic ion pairs with hydrophilic macromolecular drugs.

Abstract

WORKING HYPOTHESIS:

It was the hypothesis of this study that esters of arginine (Arg) with medium and long chain aliphatic alcohols are biodegradable and less cytotoxic than well-established cationic surfactants being used for hydrophobic ion pairing (HIP) with hydrophilic macromolecular drugs.

EXPERIMENTS:

Arg was linked to nonan-1-ol and hexadecan-1-ol (C9 and C16) via an ester linkage. The newly formed Arg-nonyl ester (ANE) and Arg-hexadecanoyl ester (AHE) surfactants were evaluated regarding critical micelle concentration (CMC) using pyrene fluorescent method, cytotoxicity on human colorectal adenocarcinoma-derived cells (Caco-2) and biodegradability at the concentrations of 2.5 and 5 mg/mL using 2500 Nα-benzoyl-l-arginine ethyl ester hydrochloride (BAEE) units/mL of trypsin. Furthermore, in order to evaluate their potential for HIP, heparin and daptomycin were used as model polysaccharide and peptide drugs, respectively.

FINDINGS:

Chemical structures of ANE and AHE surfactants were confirmed by FTIR, 1H NMR, and LC-MS. CMC of ANE was 7.5 mM and CMC of AHE was 2 mM. Arg-surfactants were not cytotoxic below their CMC. At CMC and above CMC, ANE was significantly (P < 0.05) more cytotoxic than AHE. ANE in both concentrations was degraded ˃98% within 48 h. The degradation of AHE at lower concentration was ˃97% and about 50% at higher concentration. Arg-surfactants were able to efficiently precipitate heparin and daptomycin from corresponding aqueous solutions.

CONCLUSION:

Arg-surfactants being biodegradable and less toxic seems to be a promising alternative to well-established cationic surfactants for the formation of hydrophobic ion pairs (HIPs) with hydrophilic macromolecular drugs.

• Authors: Iram Shahzadi, Mulazim Hussain Asim, Aida Dizdarević, Julian Dominik Wolf, Markus Kurpiers, Barbara Matuszczak, Andreas Bernkop-Schnürch
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 552 Pg. 287-294 (Sep 15 2019) ISSN: 1095-7103 [Electronic] United States
• PMID: 31132631 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Ions
• Macromolecular Substances
• Micelles
• Surface-Active Agents
• Arginine
• Daptomycin

Topics

• Arginine (analogs & derivatives, chemistry, pharmacology)
• Caco-2 Cells
• Cell Survival (drug effects)
• Daptomycin (chemistry)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Ions (chemistry)
• Macromolecular Substances (chemistry)
• Micelles
• Molecular Conformation
• Surface-Active Agents (chemistry, pharmacology)