Glargine insulin loaded lipid nanoparticles: Oral delivery of liquid and solid oral dosage forms.
Administration, Oral
Animals
Biomarkers
/ blood
Blood Glucose
/ drug effects
Capsules
Diabetes Mellitus, Experimental
/ blood
Drug Carriers
Drug Compounding
Hypoglycemic Agents
/ administration & dosage
Insulin Glargine
/ administration & dosage
Lipids
/ chemistry
Male
Nanoparticles
Pharmaceutical Solutions
Rats, Wistar
Streptozocin
Tablets
Insulin therapy
Nanostructured lipid carrier
Oral therapies
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
08 02 2021
08 02 2021
Historique:
received:
22
05
2020
revised:
10
09
2020
accepted:
15
09
2020
pubmed:
3
11
2020
medline:
18
3
2021
entrez:
2
11
2020
Statut:
ppublish
Résumé
The oral administration of insulin has so far been precluded by gastro-intestinal enzyme degradation and poor intestinal absorption. Preliminary evidence for peptide uptake by the gut has recently been obtained, by our research group, following the administration of nanostructured lipid-carrier suspensions loaded with glargine insulin in healthy animal models. In this experimental study, glargine insulin-loaded nanostructured lipid carriers have been converted into solid oral dosage forms (tablets, capsules), that are more suitable for administration in humans and have prolonged shelf-life. The liquid and solid oral dosage forms were tested for glargine insulin uptake and glucose responsivity in healthy and streptozotocin-induced diabetic rats (6 animals in each group). A suitable composition gave redispersible solid oral dosage forms from glargine insulin-loaded carriers, using both spray-drying and freeze-drying. It was observed that the liquid and solid formulations had relevant hypoglycaemic effects in healthy rats, while only capsules were efficacious in diabetic rats; probably because of gut alterations in these animal models. Detected glargine insulinaemia was consistent with a glycaemic profile. The formulations under study showed their potential as oral glucose-lowering agents, particularly when used as capsules. However, further study is needed to produce a useful orally-active insulin preparation.
Sections du résumé
BACKGROUND AND AIMS
The oral administration of insulin has so far been precluded by gastro-intestinal enzyme degradation and poor intestinal absorption. Preliminary evidence for peptide uptake by the gut has recently been obtained, by our research group, following the administration of nanostructured lipid-carrier suspensions loaded with glargine insulin in healthy animal models.
METHODS AND RESULTS
In this experimental study, glargine insulin-loaded nanostructured lipid carriers have been converted into solid oral dosage forms (tablets, capsules), that are more suitable for administration in humans and have prolonged shelf-life. The liquid and solid oral dosage forms were tested for glargine insulin uptake and glucose responsivity in healthy and streptozotocin-induced diabetic rats (6 animals in each group). A suitable composition gave redispersible solid oral dosage forms from glargine insulin-loaded carriers, using both spray-drying and freeze-drying. It was observed that the liquid and solid formulations had relevant hypoglycaemic effects in healthy rats, while only capsules were efficacious in diabetic rats; probably because of gut alterations in these animal models. Detected glargine insulinaemia was consistent with a glycaemic profile.
CONCLUSION
The formulations under study showed their potential as oral glucose-lowering agents, particularly when used as capsules. However, further study is needed to produce a useful orally-active insulin preparation.
Identifiants
pubmed: 33131992
pii: S0939-4753(20)30407-5
doi: 10.1016/j.numecd.2020.09.020
pii:
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Capsules
0
Drug Carriers
0
Hypoglycemic Agents
0
Lipids
0
Pharmaceutical Solutions
0
Tablets
0
Insulin Glargine
2ZM8CX04RZ
Streptozocin
5W494URQ81
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
691-698Informations de copyright
Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors state that they have no conflict of interest concerning this manuscript.