Nano-in-nano enteric protein delivery system: coaxial Eudragit® L100-55 fibers containing poly(N-vinylcaprolactam) nanogels

Oral protein delivery holds significant promise as an effective therapeutic strategy for treating a wide range of diseases. However, effective absorption of proteins faces challenges due to biological barriers such as harsh conditions of the stomach and the low permeability of mucous membranes. To address these challenges, this article presents a novel nano-in-nano platform designed for enteric protein delivery. This platform, obtained by electrospinning, involves a coaxial arrangement comprising poly(N-vinylcaprolactam) nanogels (NGs) enclosed within nanofibers of Eudragit (R) L100-55 (EU), a pH-responsive polymer. The pH-selective solubility of EU ensures the protection of NGs during their passage through the stomach, where the fibers remain intact at low pH, and releases them in the intestine where EU dissolves. The switchable characteristic of this nano-in-nano platform is confirmed by using NGs loaded with a model protein (ovalbumin), which is selectively released when the intestinal pH is achieved. The versatility of this nano-in-nano delivery platform is demonstrated by the ability to modify the fibers dissolution profile simply by adjusting the concentration of EU used in the electrospinning process. Furthermore, by tuning the properties of NGs, the potential applications of this platform can be further extended, paving the way for diverse therapeutic possibilities.