TY - JOUR
T1 - Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model
AU - Shrestha, Neha
AU - Araújo, Francisca
AU - Shahbazi, Mohammad Ali
AU - Mäkilä, Ermei
AU - Gomes, Maria João
AU - Airavaara, Mikko
AU - Kauppinen, Esko I.
AU - Raula, Janne
AU - Salonen, Jarno
AU - Hirvonen, Jouni
AU - Sarmento, Bruno
AU - Santos, Hélder A.
PY - 2016/6/28
Y1 - 2016/6/28
N2 - Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~ 2 min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~ 6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1 + DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.
AB - Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~ 2 min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~ 6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1 + DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.
KW - Chitosan
KW - Dipeptidyl peptidase-4
KW - Ex vivo
KW - Glucagon-like peptide-1
KW - In vivo
KW - Oral delivery
KW - Porous silicon nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84964284748&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.04.024
DO - 10.1016/j.jconrel.2016.04.024
M3 - Article
AN - SCOPUS:84964284748
VL - 232
SP - 113
EP - 119
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -