Nano-in-nano enteric delivery sytem

SONZOGNI, ANA SOFÍA; RIVERO, GUADALUPE; MINARI, ROQUE; GONZALEZ, VERÓNICA; ABRAHAM, GUSTAVO A.; CALDERÓN, MARCELO

San Sebastián

Conferencia; 3° Spanish conference on Biomedical Applications of Nanomaterials; 2021

The use of nanoparticles to selectively deliver therapeutics to specific sites has been the key for achieving effective treatments and reducing adverse effects. Nanogels (NGs), polymer crosslinked nanoparticles, have a leading role in controlled and targeted release, because they offer high water retention resulting in high loading capabilities, stability in biological fluids and biocompatibility. But despite their great advantages, their used for oral delivery is limited due to their large exposed area and porosity that do not allow to protect their cargo from the extreme conditions of the stomach. In this work, the development of a nano-in-nano polymer system for protein enteric delivery is presented. The system is composed by coaxial nanofibers formed by a continuous Eudragit L100-55 (EU) sheath that covers inset poly(N-vinylcaprolactam) NGs (Figure 1). The EU selective solubility throughout the gastrointestinal tract protects NGs during their passage through the stomach, where fibers will remain keep, and releases them in the duodenum (pH 6) where the EU dissolves. NGs were synthesized with N-vinylcaprolactam and N,N-methylenebisacrylamide as crosslinker. NGs are thermoresponsive, with a collapsed size of 142.9 nm (PDI 0.058) and transition temperature of 32.5 °C. They are not cytotoxic and able to load a model protein (ovalbumin, OVA) with a loading capacity of 0.963 mgOVA/mgNGs and temperature dependent release. Fibers were prepared by coaxial electrospinning with a NGs concentration of 10 mg/mL. Optimization of the compositional and processing parameters involved (EU concentration of 150 and 200 mg/mL, solvents and flow rates of both components and voltage, etc) led to nanometric fibers with smooth uniform morphology. As expected, fibers fabricated with higher flow rates and EU concentration present larger diameters. FTIR analysis confirmed the presence of NGs and OVA in the fibers. Fibers demonstrated to resist without dissolving 2 h at pH 1.2 and dissolving at pH 6.8 before 2 h, pH conditions of stomach and intestine.2 Results envisage the potential of the proposal as platform for oral delivery of proteins.