Control-Release Polyethylenimine-Modified Fibroin Nanoparticles As A Potential Vehicle for the Oral Delivery of Quercetin

Polyphenolic compounds are a big class of chemicals employed in numerous biomedical applications. However, these compounds are susceptible to degradations, especially in the varied gastrointestinal pH, which hinders their use in oral administrations. Thus, this work developed fibroin nanoparticles (FNP) and polyethylenimine-modified FNP (PEI-FNP) to orally protect and deliver quercetin (QC), a model polyphenol. The particles were formulated using two distinct methods: adsorption and co-condensation. Both formulas showed appropriate physicochemical properties for oral administrations, including nano-sizes (~700 nm for FNP-QC and ~200 nm for PEI-FNP-QC), narrow size distribution (polydispersity index < 0.3), adjustable zeta potentials (~-20 mV for FNP-QC and ~+25 mV for PEI-FNP-QC), enhanced QC aqueous solubility to 2-3 times, and observable chemical interactions (hydrogen bonding and ionic interactions) between QC and fibroin/PEI. Moreover, depending on the formulation process and particle compositions, the particles possessed moderate QC entrapment efficiency (35-75%), smooth/rough surfaces, and rapid drug adsorption followed models including Langmuir and Dubinin-Radushkevich isotherms, as well as pseudo-second-order kinetics. Interestingly, in the mimicked oral condition, the particles can protect QC from the gastric condition at pH 1.2, with less than 20% QC release, while sustaining its release in the intestine at pH 6.8, with the release rates that could be favorably controlled by varying the formulation methods and/or PEI functionalization. In summary, the FNP and PEI-FNP demonstrated much potential as release-controllable delivery systems for oral administrations of polyphenolic compounds.