Chitosan - Polyphosphate nanoparticles for a targeted drug release at the absorption membrane

The aim of this study was to develop nanoparticles (NPs) providing a targeted drug release directly on the epithelium of the intestinal mucosa. NPs were prepared via ionic gelation between cationic chitosan (Cs) and anionic polyphosphate (PP). The resulting NPs were characterized by their size, polydispersity index (PDI) and zeta potential. Isolated and cellassociated intestinal alkaline phosphatase (IAP) was employed to trigger polyphosphate cleavage in Cs-PP NPs which was quantified via malachite green assay. In parallel, the shift in zeta potential was determined. In-vitro drug release studies were performed in Franz diffusion cells with Cs-PP NPs containing rhodamine 123 as model active ingredient. Furthermore, cytotoxicity of Cs-PP NPs was assessed via resazurin assay on Caco-2 cells as well as via hemolysis assay on red blood cells. Cs-PP NPs exhibited an average size of 144.17 +/- 10.95 nm and zeta potential of -12.6 +/- 0.50 mV. The encapsulation efficiency of rhodamine 123 by Cs-PP NPs was 86.8%. After incubation with isolated IAP for 3 h the polyphosphate of Cs-PP NPs was cleaved to monophosphate and zeta potential raised up to -2.3 +/- 0.30 mV. Cs-PP NPs showed a non-toxic profile. Within 3 h, 62.0 +/- 10.8% and 14.1 +/- 2.2% of total rhodamine 123 was released from Cs-PP NPs upon incubation with isolated as well as porcine intestine derived intestinal alkaline phosphatase (IAP), respectively. According to these results, Cs-PP NPs are promising drug delivery systems to enable a drug targeted release at the absorption membrane.

Automated summary

The aim of this study was to develop nanoparticles that can release drugs directly on the epithelium of the intestinal mucosa. These nanoparticles were prepared by using ionic gelation between chitosan and polyphosphate. The characteristics of the nanoparticles were analyzed, and their drug release ability and cytotoxicity were evaluated. The results showed that these nanoparticles have the potential to deliver drugs on the absorption membrane without causing toxicity.