TY - JOUR
T1 - Film-nanoparticle composite for enhanced oral delivery of alpha-casozepine
AU - Castro, Pedro M.
AU - Baptista, Patrícia
AU - Zuccheri, Giampaolo
AU - Madureira, Ana Raquel
AU - Sarmento, Bruno
AU - Pintado, Manuela E.
N1 - Funding Information:
The research work that is exposed in this manuscript support granted by national founds from Fundação para a Ciência e Tecnologia through project PTDC/BBB-NAN/3249/2014. Pedro M. Castro would like to thank Comissão de Coordenação e Desenvolvimento Regional do Norte (CCDR-N), Portugal, for his PhD grant (NORTE-08-5369-FSE-000007). This work was also s supported by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).
Funding Information:
This work was also s supported by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020) , under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).
Publisher Copyright:
© 2019
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Whey-derived alpha-casozepine bioactive peptide (YLGYLEQLLR) was associated with previously optimized guar-gum film-PLGA nanoparticles, aiming to increase both stability across gastrointestinal tract and permeability across absorptive epithelia. Oral films associated with nanoparticles (FNp) enhance buccal absorption along with protection of carried bioactive molecules that are swallowed, with inherent increase of bioavailability. None of developed formulations induced significant loss of cell viability. Permeability across both buccal and intestinal cell barriers was enhanced when alpha-casozepine was carried by FNp system, when compared with film and nanoparticles alone, in a simulated gastrointestinal tract environment. Moreover, differences in permeability profile across buccal and intestinal epithelia were in accordance with the slower erosion of PLGA nanoparticles in a media of neutral pH, resembling oral cavity conditions, and a faster erosion in acidic conditions, as occurs in stomach, as observed by a continuous analysis of nanoparticle morphology over 980 min by atomic force microscopy. Additionally, apparent permeability of alpha-casozepine across TR146 human buccal carcinoma cells and Caco-2/HT29-MTX co-culture, carried by FNp was indeed superior when compared with peptide loaded in PLGA nanoparticles and in films alone or with free peptide control solution. Both FNp and PLGA nanoparticles alone enhanced the permeability of relaxing peptide compared with guar-gum films alone. An increased tongue adhesion when PLGA nanoparticles were added to the guar-gum films was also observed. Developed formulations improved both buccal an intestinal absorption of carried bioactive molecules without compromising cell viability.
AB - Whey-derived alpha-casozepine bioactive peptide (YLGYLEQLLR) was associated with previously optimized guar-gum film-PLGA nanoparticles, aiming to increase both stability across gastrointestinal tract and permeability across absorptive epithelia. Oral films associated with nanoparticles (FNp) enhance buccal absorption along with protection of carried bioactive molecules that are swallowed, with inherent increase of bioavailability. None of developed formulations induced significant loss of cell viability. Permeability across both buccal and intestinal cell barriers was enhanced when alpha-casozepine was carried by FNp system, when compared with film and nanoparticles alone, in a simulated gastrointestinal tract environment. Moreover, differences in permeability profile across buccal and intestinal epithelia were in accordance with the slower erosion of PLGA nanoparticles in a media of neutral pH, resembling oral cavity conditions, and a faster erosion in acidic conditions, as occurs in stomach, as observed by a continuous analysis of nanoparticle morphology over 980 min by atomic force microscopy. Additionally, apparent permeability of alpha-casozepine across TR146 human buccal carcinoma cells and Caco-2/HT29-MTX co-culture, carried by FNp was indeed superior when compared with peptide loaded in PLGA nanoparticles and in films alone or with free peptide control solution. Both FNp and PLGA nanoparticles alone enhanced the permeability of relaxing peptide compared with guar-gum films alone. An increased tongue adhesion when PLGA nanoparticles were added to the guar-gum films was also observed. Developed formulations improved both buccal an intestinal absorption of carried bioactive molecules without compromising cell viability.
KW - Alpha-casozepine
KW - Buccal delivery
KW - Oral delivery
KW - Oral films
KW - PLGA nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85065906663&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2019.05.029
DO - 10.1016/j.colsurfb.2019.05.029
M3 - Article
C2 - 31128515
AN - SCOPUS:85065906663
SN - 0927-7765
VL - 181
SP - 149
EP - 157
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -