RT Journal Article
T1 Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers
A1 Niu, Zhigao
A1 Tedesco, Erik
A1 Benetti, Federico
A1 Mabondzo, Aloïse
A1 Montagner, Isabella Monia
A1 Marigo, Ilaria
A1 González Touceda, David
A1 Tovar Carro, Sulay A.
A1 Diéguez González, Carlos
A1 Santander Ortega, Manuel J.
A1 Alonso Fernández, María José
K1 Polyarginine
K1 Nanocapsule
K1 Insulin
K1 Permeation enhancer
K1 Oral peptide delivery
AB The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180 nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80–90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for > 4 h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptides
PB Elsevier
SN 0168-3659
YR 2017
FD 2017
LK http://hdl.handle.net/10347/21607
UL http://hdl.handle.net/10347/21607
LA eng
NO Niu, Z., Tedesco, E., Benetti, F., Mabondzo, A., Montagner, I., & Marigo, I. et al. (2017). Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers. Journal Of Controlled Release, 263, 4-17. doi: 10.1016/j.jconrel.2017.02.024
NO This work was supported by the European TRANS-INT Consortium, which received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 281035. Z. Niu also would like to thank the Chinese Scholarship Council for his scholarship
DS Minerva
RD 24 abr 2026