The impact of gastrointestinal mucus on nanoparticle penetration - in vitro evaluation of mucus-penetrating nanoparticles for photodynamic therapy.
Over the last years nanoparticles (NP) have become a promising vehicle as drug delivery systems for photodynamic therapy (PDT), combining the advantages of an effective drug transport to the target cells and the reduction of undesired side effects. The in vitro evaluation of new nanoparticulate formulations has become a rising problem since cell culture models differ from the in vivo situation of the human body to a large extent. Particularly, in case of gastrointestinal tumors, after peroral application nanoparticles are challenged by overcoming the mucus layer as a first physical barrier before reaching the target cells, an aspect often neglected in literature. However, the presence of mucus is crucial for in vitro models to evaluate mucus-penetrating potential of surface-modified nanoparticulate drug carrier systems. Biodegradable poly(dl-lactide-co-glycolide) (PLGA) NP loaded with the model photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) were surface modified with either poly(ethylene glycol) (PEG) or chitosan (CS) to gain mucus-penetrating or mucoadhesive particle properties. All NP systems were compared to each other and to free mTHPP regarding cytotoxicity and cellular uptake in HT-29 cells and mucus producing HT-29-MTX cells. For PEGylated mTHPP-PLGA-PEG-NP a significantly higher accumulation was obtained in HT-29-MTX cells compared to all other tested nanoparticles and the free drug. Additionally, a mucus-containing Transwell® model, consisting of HT-29-MTX cells, confirmed these results, representing a promising in vitro screening method for mucus-penetrating particle properties.
['Mahlert|Laura|L|', 'Anderski|Juliane|J|', 'Mulac|Dennis|D|', 'Langer|Klaus|K|']
D045744:Cell Line, Tumor D041981:Gastrointestinal Tract D006801:Humans D009093:Mucus D053758:Nanoparticles D010778:Photochemotherapy D017319:Photosensitizing Agents D011092:Polyethylene Glycols D000077182:Polylactic Acid-Polyglycolic Acid Copolymer D011166:Porphyrins
Nanoparticles Photodynamic therapy PLGA Cellular uptake HT-29-MTX Cell model Co-culture Intestinal cancer Mucus penetration Poly (ethylene glycol)