From [Chitosan DNA nanoparticles for oral gene delivery](https://www.wjgnet.com/2220-3184/full/v6/i3/22.htm): > Free DNA is quickly denatured by the acidic pH in the stomach and intestinal and cellular enzymes, so it would have no therapeutic effect[6]. However, chitosan-coupled therapeutic DNA sequences formulated as chitosan nanoparticles are effectively protected from various physiological and cellular barriers. Acidity > > pH varies greatly in the gastrointestinal tract, ranging from the extremely acidic stomach (mean pH 1.7) to the slightly alkaline ileum (mean pH 7.5) (Figure 2A)[14-16]. Chitosan nanoparticles have been shown to protect enclosed nucleic acids across a wide range of pH. > ... > Therefore, chitosan (pKa 6.5) is able to withstand a wide pH range from 1.5 (highly stabilized) to 6.8 (intermediate stability - optimal for transfection), before becoming destabilized and aggregating. In support of this model, ex vivo experiments on gastrointestinal tissue internalization of chitosan nanoparticles found internalization to be higher for the jejunum (pH 6.6) than the ileum (pH 7.5 - too basic) and duodenum (pH 6.1 - too acidic)[24].