Hung Thanh Lam1, Nguyet-Minh Nguyen Le2, Thi Nhu Quynh Phan3, Andreas Bernkop-Schnürch4. 1. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria / Europe; Department of Pharmaceutical Technology, Faculty of Pharmacy, Can Tho University of Medicine and Pharmacy, Can Tho City, Vietnam. 2. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria / Europe; Department of Industrial Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. 3. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria / Europe; Faculty of Pharmacy, University of Medicine and Pharmacy, Hue University, Vietnam. 4. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria / Europe. Electronic address: andreas.bernkop@uibk.ac.at.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: SEDDS loaded with proteinase/BAK complexes are promising nanocarriers because of enhanced mucus permeating properties.
AIM: 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. METHODS: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. RESULTS: 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. CONCLUSION:SEDDS loaded with proteinase/BAK complexes are promising nanocarriers because of enhanced mucus permeating properties.