PMID- 27091697 OWN - NLM STAT- MEDLINE DCOM- 20171220 LR - 20210927 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 232 DP - 2016 Jun 28 TI - Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model. PG - 113-9 LID - S0168-3659(16)30225-5 [pii] LID - 10.1016/j.jconrel.2016.04.024 [doi] 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 (~2min). 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Shrestha, Neha AU - Shrestha N AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland. Electronic address: neha.shrestha@helsinki.fi. FAU - Araujo, Francisca AU - Araujo F AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland; i3S - Instituto de Investigacao e Inovacao em Saude and INEB - Instituto Nacional de Engenharia Biomedica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS - Instituto Ciencias Biomedicas Abel Salazar, University of Porto, Portugal. FAU - Shahbazi, Mohammad-Ali AU - Shahbazi MA AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland. FAU - Makila, Ermei AU - Makila E AD - Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014, Finland. FAU - Gomes, Maria Joao AU - Gomes MJ AD - i3S - Instituto de Investigacao e Inovacao em Saude and INEB - Instituto Nacional de Engenharia Biomedica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS - Instituto Ciencias Biomedicas Abel Salazar, University of Porto, Portugal. FAU - Airavaara, Mikko AU - Airavaara M AD - Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland. FAU - Kauppinen, Esko I AU - Kauppinen EI AD - Department of Applied Physics, Aalto University School of Science, FI-00076, Finland. FAU - Raula, Janne AU - Raula J AD - Department of Applied Physics, Aalto University School of Science, FI-00076, Finland. FAU - Salonen, Jarno AU - Salonen J AD - Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014, Finland. FAU - Hirvonen, Jouni AU - Hirvonen J AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland. FAU - Sarmento, Bruno AU - Sarmento B AD - i3S - Instituto de Investigacao e Inovacao em Saude and INEB - Instituto Nacional de Engenharia Biomedica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; CESPU, Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude, 4585-116 Gandra, Portugal. FAU - Santos, Helder A AU - Santos HA AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland. Electronic address: helder.santos@helsinki.fi. LA - eng GR - 310892/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160416 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 71138-97-1 (hydroxypropylmethylcellulose acetate succinate) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9004-67-5 (Methylcellulose) RN - 9012-76-4 (Chitosan) RN - Z4152N8IUI (Silicon) SB - IM MH - Administration, Oral MH - Animals MH - Blood Glucose/analysis MH - Chitosan/chemistry MH - Diabetes Mellitus, Experimental/blood/*drug therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage/chemistry/therapeutic use MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1/*administration & dosage/chemistry/therapeutic use MH - Intestine, Small/metabolism MH - Methylcellulose/analogs & derivatives/chemistry MH - Nanocomposites/*administration & dosage/chemistry/therapeutic use MH - Nanoparticles/chemistry MH - Rats, Wistar MH - Silicon/chemistry OTO - NOTNLM OT - Chitosan OT - Dipeptidyl peptidase-4 OT - Ex vivo OT - Glucagon-like peptide-1 OT - In vivo OT - Oral delivery OT - Porous silicon nanoparticles EDAT- 2016/04/20 06:00 MHDA- 2017/12/21 06:00 CRDT- 2016/04/20 06:00 PHST- 2016/01/30 00:00 [received] PHST- 2016/04/13 00:00 [revised] PHST- 2016/04/14 00:00 [accepted] PHST- 2016/04/20 06:00 [entrez] PHST- 2016/04/20 06:00 [pubmed] PHST- 2017/12/21 06:00 [medline] AID - S0168-3659(16)30225-5 [pii] AID - 10.1016/j.jconrel.2016.04.024 [doi] PST - ppublish SO - J Control Release. 2016 Jun 28;232:113-9. doi: 10.1016/j.jconrel.2016.04.024. Epub 2016 Apr 16.