Oral insulin delivery using nanoparticles based on microemulsions with different structure-types: optimisation and in vivo evaluation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Oral insulin delivery using nanoparticles based on microemulsions with different structure-types : optimisation and in vivo evaluation. / Graf, Anja; Rades, Thomas; Hook, Sarah M.
In: European Journal of Pharmaceutical Sciences, Vol. 37, No. 1, 2009, p. 53-61.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Oral insulin delivery using nanoparticles based on microemulsions with different structure-types
T2 - optimisation and in vivo evaluation
AU - Graf, Anja
AU - Rades, Thomas
AU - Hook, Sarah M
PY - 2009
Y1 - 2009
N2 - The purpose of this study was to optimise entrapment of insulin in poly(alkylcyanoacrylate) nanoparticles prepared from microemulsions with different microstructure containing isopropyl myristate, caprylocaproyl macrogolglycerides, polyglyceryl oleate and insulin solution and to investigate the in vitro release and bioactivity of insulin in nanoparticles dispersed in the microemulsion templates. Entrapment efficiency and release of insulin were studied using a reverse-phase HPLC assay. Morphology of the nanoparticles was examined with scanning electron microscopy. Bioactivity of insulin was studied using a streptozotocin-diabetic rat model. Nanoparticles were spherical with 200-400 nm in size without significant difference between different microemulsion templates, types and amounts of monomer. Entrapment efficiency increased significantly with increasing monomer concentration but decreased with increasing aqueous fraction in the microemulsion template. Insulin loading however, showed an opposite trend. In vitro release profiles of insulin from the nanoparticles dispersed in the microemulsion templates were controlled by the monomer concentration only. In vivo, a consistent and significant hypoglycemic effect over controls was found for up to 36 h depending on the type of monomer. No significant serum insulin levels were detectable. This study showed that the strategy of delivering insulin orally, entrapped in nanoparticles and dispersed in a biocompatible microemulsion is promising and highlights the importance of optimisation studies in combination with in vivo experiments.
AB - The purpose of this study was to optimise entrapment of insulin in poly(alkylcyanoacrylate) nanoparticles prepared from microemulsions with different microstructure containing isopropyl myristate, caprylocaproyl macrogolglycerides, polyglyceryl oleate and insulin solution and to investigate the in vitro release and bioactivity of insulin in nanoparticles dispersed in the microemulsion templates. Entrapment efficiency and release of insulin were studied using a reverse-phase HPLC assay. Morphology of the nanoparticles was examined with scanning electron microscopy. Bioactivity of insulin was studied using a streptozotocin-diabetic rat model. Nanoparticles were spherical with 200-400 nm in size without significant difference between different microemulsion templates, types and amounts of monomer. Entrapment efficiency increased significantly with increasing monomer concentration but decreased with increasing aqueous fraction in the microemulsion template. Insulin loading however, showed an opposite trend. In vitro release profiles of insulin from the nanoparticles dispersed in the microemulsion templates were controlled by the monomer concentration only. In vivo, a consistent and significant hypoglycemic effect over controls was found for up to 36 h depending on the type of monomer. No significant serum insulin levels were detectable. This study showed that the strategy of delivering insulin orally, entrapped in nanoparticles and dispersed in a biocompatible microemulsion is promising and highlights the importance of optimisation studies in combination with in vivo experiments.
U2 - 10.1016/j.ejps.2008.12.017
DO - 10.1016/j.ejps.2008.12.017
M3 - Journal article
C2 - 19167488
VL - 37
SP - 53
EP - 61
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
SN - 0928-0987
IS - 1
ER -
ID: 40353247