PMID- 27150301
OWN - NLM
STAT- MEDLINE
DCOM- 20180914
LR  - 20231111
IS  - 2040-3372 (Electronic)
IS  - 2040-3364 (Print)
IS  - 2040-3364 (Linking)
VI  - 8
IP  - 20
DP  - 2016 May 19
TI  - 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.
PG  - 10706-13
LID - 10.1039/c6nr00294c [doi]
AB  - 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.
FAU - Araujo, F
AU  - Araujo F
AD  - I3S - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 
      4200-135 Porto, Portugal. bruno.sarmento@ineb.up.pt and INEB - Instituto de 
      Engenharia Biomedica, Universidade do Porto, 4200-135 Porto, Portugal and ICBAS - 
      Instituto Ciencias Biomedicas Abel Salazar, Universidade do Porto, 4150-180 
      Porto, Portugal and Division of Pharmaceutical Chemistry and Technology, Faculty 
      of Pharmacy, University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Shrestha, N
AU  - Shrestha N
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Gomes, M J
AU  - Gomes MJ
AD  - I3S - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 
      4200-135 Porto, Portugal. bruno.sarmento@ineb.up.pt and INEB - Instituto de 
      Engenharia Biomedica, Universidade do Porto, 4200-135 Porto, Portugal and ICBAS - 
      Instituto Ciencias Biomedicas Abel Salazar, Universidade do Porto, 4150-180 
      Porto, Portugal.
FAU - Herranz-Blanco, B
AU  - Herranz-Blanco B
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Liu, D
AU  - Liu D
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Hirvonen, J J
AU  - Hirvonen JJ
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Granja, P L
AU  - Granja PL
AD  - I3S - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 
      4200-135 Porto, Portugal. bruno.sarmento@ineb.up.pt and INEB - Instituto de 
      Engenharia Biomedica, Universidade do Porto, 4200-135 Porto, Portugal and ICBAS - 
      Instituto Ciencias Biomedicas Abel Salazar, Universidade do Porto, 4150-180 
      Porto, Portugal.
FAU - Santos, H A
AU  - Santos HA
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki, FI-00790 Helsinki, Finland.
FAU - Sarmento, B
AU  - Sarmento B
AD  - I3S - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, 
      4200-135 Porto, Portugal. bruno.sarmento@ineb.up.pt and INEB - Instituto de 
      Engenharia Biomedica, Universidade do Porto, 4200-135 Porto, Portugal and CESPU, 
      Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude, 
      4585-116 Gandra, Portugal.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nanoscale
JT  - Nanoscale
JID - 101525249
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Animals
MH  - Blood Glucose
MH  - Diabetes Mellitus, Experimental/drug therapy
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Glucagon-Like Peptide 1/*antagonists & inhibitors
MH  - Hypoglycemic Agents/*administration & dosage
MH  - Insulin
MH  - Male
MH  - *Microfluidics
MH  - Rats
MH  - Rats, Wistar
PMC - PMC5047059
EDAT- 2016/05/07 06:00
MHDA- 2018/09/15 06:00
PMCR- 2016/04/20
CRDT- 2016/05/07 06:00
PHST- 2016/05/07 06:00 [entrez]
PHST- 2016/05/07 06:00 [pubmed]
PHST- 2018/09/15 06:00 [medline]
PHST- 2016/04/20 00:00 [pmc-release]
AID - c6nr00294c [pii]
AID - 10.1039/c6nr00294c [doi]
PST - ppublish
SO  - Nanoscale. 2016 May 19;8(20):10706-13. doi: 10.1039/c6nr00294c.