The aim of this study was to develop peptide antibiotic–polyphosphate
nanoparticles that are able to overcome the enzymatic and mucus barriers
providing a targeted drug release directly on the intestinal epithelium.
Polymyxin B–polyphosphate nanoparticles (PMB–PP NPs)
were formed via ionic gelation between the cationic peptide and the
anionic polyphosphate (PP). The resulting NPs were characterized by
particle size, polydispersity index (PDI), zeta potential, and cytotoxicity
on Caco-2 cells. The protective effect of these NPs for incorporated
PMB was evaluated via enzymatic degradation studies with lipase. Moreover,
mucus diffusion of NPs was investigated with porcine intestinal mucus.
Isolated intestinal alkaline phosphatase (IAP) was employed to trigger
the degradation of NPs and consequent drug release. PMB–PP
NPs exhibited an average size of 197.13 ± 14.13 nm, a PDI of
0.36, a zeta potential of −11.1 ± 3.4 mV and a concentration
and time-dependent toxicity. They provided entire protection toward
enzymatic degradation and exhibited significantly (p< 0.05) higher mucus permeating properties than PMB. When incubated
with isolated IAP for 4 h, monophosphate and PMB were constantly released
from PMB–PP NPs and zeta potential raised up to −1.9
± 0.61 mV. According to these findings, PMB–PP NPs are
promising delivery systems to protect cationic peptide antibiotics
against enzymatic degradation, to overcome the mucus barrier and to
provide drug release directly at the epithelium.