Molecular confinement of human amylin in lipidic nanoparticles.
Amylin is a pancreatic hormone involved in the regulation of glucose metabolism and homeostasis. Restoration of the post-prandial and basal levels of human amylin in diabetic individuals is a key in controlling glycemia, controlling glucagon, reducing the insulin dose and increasing satiety, among other physiologic functions. Human amylin has a high propensity to aggregate. We have addressed this issue by designing a liposomal human amylin formulation. Nanoparticles of multilamellar liposomes comprising human amylin were obtained with 53% encapsulation efficiency. The in vitro kinetic release assay shows a biphasic profile. The stabilization of the lipidic nanoparticle against freeze-drying was achieved by using mannitol as a cryoprotectant, as evidenced by morphological characterization. The effectiveness of the human amylin entrapped in lipidic nanoparticles was tested by the measurement of its pharmacological effect in vivo after subcutaneous administration in mice. Collectively these results demonstrate the compatibility of human amylin with the lipidic interface as an effective pharmaceutical delivery system.
a Federal University of Rio de Janeiro - UFRJ , Rio de Janeiro , RJ , Brazil .|b Federal Institute of Science and Technology of Rio de Janeiro - IFRJ , Rio de Janeiro , RJ , Brazil .
Raquel Rennó
RR
Braga
b Federal Institute of Science and Technology of Rio de Janeiro - IFRJ , Rio de Janeiro , RJ , Brazil .
Luciana
L
Almeida
c Department of Chemistry , Institute of Exact Sciences, Rural Federal University of Rio de Janeiro - UFRRJ , Seropédica , RJ , Brazil .
Luiz Henrique
LH
Guerreiro
c Department of Chemistry , Institute of Exact Sciences, Rural Federal University of Rio de Janeiro - UFRRJ , Seropédica , RJ , Brazil .
Priscilla
P
Tinoco
a Federal University of Rio de Janeiro - UFRJ , Rio de Janeiro , RJ , Brazil .|d Laboratory for Macromolecules (LAMAC-DIMAV) , Brazilian National Institute of Metrology, Quality and Technology - INMETRO , Rio de Janeiro , RJ , Brazil , and.
Kildare R
KR
Miranda
a Federal University of Rio de Janeiro - UFRJ , Rio de Janeiro , RJ , Brazil .
Carolina A
CA
Braga
d Laboratory for Macromolecules (LAMAC-DIMAV) , Brazilian National Institute of Metrology, Quality and Technology - INMETRO , Rio de Janeiro , RJ , Brazil , and.
Ana Paula
AP
Gadelha
a Federal University of Rio de Janeiro - UFRJ , Rio de Janeiro , RJ , Brazil .
Sheila
S
Garcia
a Federal University of Rio de Janeiro - UFRJ , Rio de Janeiro , RJ , Brazil .|d Laboratory for Macromolecules (LAMAC-DIMAV) , Brazilian National Institute of Metrology, Quality and Technology - INMETRO , Rio de Janeiro , RJ , Brazil , and.|e National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro , Rio de Janeiro , RJ , Brazil.
Luis Mauricio T R
LM
Lima
D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011487:Protein Conformation
D058228:Islet Amyloid Polypeptide; D008055:Lipids
Cryoprotectant; human amylin; lipidic nanoparticles; liposomes; lyophilization; stability