Mucolytic self-emulsifying drug delivery systems (SEDDS) containing a hydrophobic ion-pair of proteinase

The aim of this study was to form hydrophobic ion-pairs of proteinase with cationic surfactants and to incorporate them into self-emulsifying drug delivery systems (SEDDS) to improve their mucus permeating properties. Proteinase was ion-paired with benzalkonium chloride (BAK), hexadecylpyridinium ch...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2021-07, Vol.162, p.105658-105658, Article 105658
Main Authors: Lam, Hung Thanh, Le, Nguyet-Minh Nguyen, Phan, Thi Nhu Quynh, Bernkop-Schnürch, Andreas
Format: Article
Language:English
Subjects:
Cationic surfactants
Hydrophobic ion-pairing
Mucus permeation
Proteinase, mucus
Self-emulsifying drug delivery systems (SEDDS)
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Summary:The aim of this study was to form hydrophobic ion-pairs of proteinase with cationic surfactants and to incorporate them into self-emulsifying drug delivery systems (SEDDS) to improve their mucus permeating properties. Proteinase was ion-paired with benzalkonium chloride (BAK), hexadecylpyridinium chloride (HDP), alkyltrimethylammonium bromide (ATA) and hexadecyltrimethylammonium bromide (HDT) at pH 8.5-9.0, and subsequently incorporated into SEDDS consisting of Cremophor EL, propylene glycol, and Capmul 808-G (40/20/40). Mucus permeation of SEDDS containing proteinase complexes was evaluated via rotating tube technique and cell-free Transwell® insert system. Additionally, enzymatic activity of proteinase complexes as well as their potential cytotoxicity was evaluated. Among all tested hydrophobic ion-pairs, proteinase/BAK showed highest potential. Mucus diffusion of SEDDS containing proteinase/BAK complex yielded in 2.3-fold and 2.5-fold higher mucus permeability with respect to blank SEDDS at Transwell® insert system and rotating tube technique, respectively. Furthermore, proteinase/BAK complex maintained the highest enzymatic activity of 50.5 ± 5.6% compared to free proteinase. At a SEDDS concentration as low as 0.006% cell viability was just 80%. The addition of proteinase complexes to SEDDS increased cytotoxicity on Caco-2 cells in a concentration-dependent manner. SEDDS loaded with proteinase/BAK complexes are promising nanocarriers because of enhanced mucus permeating properties. [Display omitted]
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2020.105658