Biodegradable arginine based steroid-surfactants: Cationic green agents for hydrophobic ion-pairing.
Int J Pharm
; 630: 122438, 2023 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-36464112
ABSTRACT
The aim of this study was to evaluate the safety and efficacy for hydrophobic ion-pairing of surfactants based on arginine (Arg). The prepared Arg-cholesteryl ester (ACE) and Arg-diosgenyl ester (ADE) were characterized regarding solubility, pKa, critical micellar concentration (CMC), biodegradability as well as membrane- and aquatic toxicity using DOTAP as reference. The ability for hydrophobic ion-pairing was evaluated and the lipophilicity of formed complexes was determined. NMR, FT-IR and MS confirmed successful synthesis of Arg-surfactants. The slightly soluble single-charged Arg-surfactants (pH < pKa3 (ACE = 10.42 ± 0.52; ADE = 10.38 ± 0.27)) showed CMCs of 27.17 µM for ACE and 35.67 µM for ADE. CMCs of the sparingly soluble double-charged species (pH < pKa2 (ACE = 5.30 ± 0.20; ADE = 5.55 ± 0.06)) were determined at concentrations of ≥ 250 µM for ACE and ≥ 850 µM for ADE. The enzymatic- and environmental biodegradability was proven by an entire cleavage of Arg-surfactants within 24 h, whereas DOTAP remained stable. Arg-surfactants exhibited lower membrane- (> 2-fold) and aquatic toxicity (> 15-fold) than DOTAP. The complexes formed with Arg-surfactants and insulin showed higher lipophilicity than the DOTAP-complex. According to these results, Arg-surfactants might be a promising safe tool for the delivery of peptide drugs.
Palabras clave
Arginine; Arginine-cholesteryl ester (ACE); Arginine-diosgenyl ester (ADE); Bicinchoninic acid; Biodegradable surfactants; Boc-Arg(boc)(2)-OH; Cholesterol; DOTAP (N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammoniummethylsulfate); Diosgenin; Eco-friendly; Green agents; Hydrophobic ion-pairing; Insulin; Oral drug delivery; Pyrene; Trypsin
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arginina
/
Tensoactivos
Idioma:
En
Revista:
Int J Pharm
Año:
2023
Tipo del documento:
Article
País de afiliación:
Austria