In vivo dual-delivery of glucagon like peptide -1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy

Show full item record



Permalink

http://hdl.handle.net/10138/224391

Citation

Araújo , F , Shrestha , N , João Gomes , M , Herranz Blanco , B , Liu , D , Hirvonen , J T , L. Granja , P , Almeida Santos , H & Sarmento , B 2016 , ' In vivo dual-delivery of glucagon like peptide -1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy ' , Nanoscale , vol. 8 , no. 20 , pp. 10706-10713 . https://doi.org/10.1039/C6NR00294C

Title: In vivo dual-delivery of glucagon like peptide -1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy
Author: Araújo, Francisca; Shrestha, Neha; João Gomes, Maria; Herranz Blanco, Bárbara; Liu, Dongfei; Hirvonen, Jouni Tapio; L. Granja, Pedro; Almeida Santos, Helder; Sarmento, Bruno
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
Date: 2016-04-19
Language: eng
Number of pages: 8
Belongs to series: Nanoscale
ISSN: 2040-3364
URI: http://hdl.handle.net/10138/224391
Abstract: Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo. Oral delivery of GLP-1 with nano- or micro-systems has been studied before, but the simultaneous nanodelivery of GLP-1 with iDPP4 is a novel strategy presented here. The type 2 diabetes mellitus (T2DM) rat model, induced through the combined administration of streptozotocin and nicotinamide, a non-obese model of T2DM, was used. The combination of both drugs resulted in an increase in the hypoglycemic effects in a sustained, but prolonged manner, where the iDPP4 improved the therapeutic efficacy of GLP-1. Four hours after the oral administration of the system, blood glucose levels were decreased by 44%, and were constant for another 4 h, representing half of the glucose area under the curve when compared to the control. An enhancement of the plasmatic insulin levels was also observed 6 h after the oral administration of the dual-drug composite system and, although no statistically significant differences existed, the amount of pancreatic insulin was also higher. These are promising results for the oral delivery of GLP-1 to be pursued further in a chronic diabetic model study.
Subject: 317 Pharmacy
221 Nano-technology
Biochemistry
Glucose
Insulin
Microfluidics
Peptides
Proteins
Nanosystems
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
c6nr00294c.pdf 654.8Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record