Mucus permeating self-emulsifying drug delivery systems (SEDDS): About the impact of mucolytic enzymes

This study aimed to improve the mucus permeating properties of self-emulsifying drug delivery systems (SEDDS) by anchoring lipidized bromelain, papain and trypsin using palmitoyl chloride. SEDDS containing enzyme-palmitate conjugates were characterized regarding droplet size and zeta potential. Their mucus permeating properties were evaluated by Transwell diffusion and rotating tube method using fluorescein diacetate (FDA) as marker. Degree of substitution of modified enzymes was 35.3%, 47.8% and 38.5% for bromelain-palmitate, papain-palmitate and trypsin-palmitate, respectively. SEDDS as control and SEDDS containing enzyme-palmitate conjugates displayed a droplet size less than 50 nm and 180-312 nm as well as a zeta potential of 3 to 4 and 4 to 5 mV, respectively. The highest percentage of permeation was achieved by introducing 5% papain-palmitate into SEDDS. It could enhance the mucus permeation of SEDDS in porcine intestinal mucus 4.6-fold and 2-fold as evaluated by Transwell diffusion and rotating tube method, respectively. It is concluded that mucus permeation of SEDDS can be strongly improved by incorporation of enzyme-palmitate conjugates. (C) 2017 Elsevier B.V. All rights reserved.