Improved Intestinal Mucus Permeation of Vancomycin via Incorporation Into Nanocarrier Containing Papain-Palmitate

The aim of this study was to improve intestinal mucus permeation of a peptide antibiotic via incorporation into papain-palmitate-modified self-emulsifying drug delivery systems (SEDDS) as nanocarrier. Vancomycin as a peptide antibiotic was lipidized by hydrophobic ion pair formation using sodium bis-2-ethylhexyl-sulphosuccinate before incorporation in SEDDS comprising Capmul MCM, propylenglycol, and Kolliphor EL (2:1:2). As mucolytic agent, 0.5% papain-palmitate was introduced in SEDDS formulation containing the vancomycin-sodium bis-2-ethylhexyl-sulphosuccinate ion pair. The formulation was evaluated regarding droplet size, zeta potential, and cytotoxicity using Caco-2 cells previous to intestinal mucus permeation studies using Transwell diffusion and rotating tube method. The hydrophobic ion pair product yielded from surfactant to drug ratio of 3:1 provided a 25-fold increase in lipophilicity, drug payload in SEDDS of 5%, and log D_{SEDDS/release medium} of 2.2. The formulation exhibited a droplet size and zeta potential of 221.5 ± 14.8 nm and -4.2 ± 0.8 mV, respectively. Cytotoxicity study showed that SEDDS formulations were not toxic. Introducing 0.5% papain-palmitate increased the mucus permeability of SEDDS 2.8-fold and 3.3-fold in Transwell diffusion and rotating tube studies, respectively. According to these results, papain decorated SEDDS might be a potential strategy to improve the mucus permeating properties of peptide antibiotics.