Mucus-penetrating nanoparticles: Promising drug delivery systems for the photodynamic therapy of intestinal cancer

Anderski J., Mahlert L., Mulac D., Langer K.

Abstract

Photodynamic therapy (PDT) is an auspicious therapy approach for the treatment of cancer. Despite its numerousbenefits, the drug delivery of the used photosensitizer (PS) to target locations inside the human bodyremains a main therapy challenge, since the standard intravenous PS injection often causes systemic side-effects.To circumvent this therapy drawback, the oral application represents a promising administration alternative.Especially for the treatment of intestinal cancer it offers the possibility of a local treatment with a reducedlikelihood for adverse drug reactions. To establish a suitable drug delivery system for intestinal PDT, we developednanoparticles (NP) of the biodegradable and biocompatible polymer poly(lactic-co-glycolic) acid(PLGA), loaded with the model PS 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP). By functionalizingthe particle surface with either poly(ethylene glycol) (PEG) or chitosan (CS), mucus-penetrating or mucoadhesiveproperties were obtained. These particle characteristics are important to enable an overcoming of theintestinal mucus barrier and thus lead to a PS accumulation close to and in the target cells. In permeation studieswith a biosimilar mucus and in cell culture experiments with mucus-covered Caco-2 cells, PEG-modified NP wereidentified as a superior drug vehicle for an intestinal PDT, compared to surface unmodified or mucoadhesive NP.