Histidine-based ionizable cationic surfactants: novel biodegradable agents for hydrophilic macromolecular drug delivery.
Drug Deliv Transl Res
; 14(9): 2370-2385, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38289467
ABSTRACT
The aim of this study was to design surfactants based on histidine (His) for hydrophobic ion-pairing and evaluate their safety and efficacy. Lauryl, palmitoyl and oleyl alcohol, as well as 2-hexyl-1-decanol were converted into surfactants with histidine as head-group via esterification. The synthesized His-surfactants were characterized regarding pKa, critical micellar concentration (CMC), biodegradability, toxicity on Caco-2 cells, and ability to provide endosomal escape. Furthermore, the suitability of these agents to be employed as counterions in hydrophobic ion pairing was evaluated. Chemical structures were confirmed by 1H-NMR, FT-IR, and MS. The synthesized surfactants showed pKa values ranging from 4.9 to 6.0 and CMC values in the range of 0.3 to 7.0 mM. Their biodegradability was proven by enzymatic cleavage within 24 h. Below the CMC, His-surfactants did not show cytotoxic effects on Caco-2 cells (cell viability > 80%). All His-surfactants showed the ability to provide endosomal escape in a pH-dependent manner in the range of 5.2 to 6.8. Complexes formed between His-surfactants and heparin or plasmid DNA (pDNA) via hydrophobic ion pairing showed at least 100-fold higher lipophilicity than the correspondent model drugs. According to these results, His-surfactants might be a promising safe tool for delivering hydrophilic macromolecular drugs and nucleic acids.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tensoativos
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Sobrevivência Celular
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Interações Hidrofóbicas e Hidrofílicas
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Histidina
Limite:
Humans
Idioma:
En
Revista:
Drug Deliv Transl Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Áustria
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA