Polymeric particles for the controlled release of human amylin.
Since its discovery the therapeutic use of the pancreatic hormone amylin has been limited due to its poor water solubility and propensity for amyloid aggregation. We have entrapped the human amylin protein in polymeric nanoparticles, using a single emulsion-solvent evaporation method and investigated its effectiveness in the controlled release of the peptide. Typical preparations composed of poly-ε-caprolactone had a mean particle size of approximately 200 nm, low polydispersity index, high protein entrapment efficiency (80%) and process yield (90%), and spherical and smooth surfaces. These nanoparticles presented a controlled release in vitro for approximately 240 h. Pharmacological evaluation in vivo by subcutaneous administration in fasting mice demonstrated the bioactivity and effectiveness of the released human amylin, resulting in reduced glycemia lasting for at least 36 h. These features indicate the potential for the use of a confined particulate system in the therapeutic controlled and sustained release of human amylin.
School of Pharmacy, Federal University of Rio de Janeiro-UFRJ, CCS, Rio de Janeiro, RJ, Brazil.
Luiz Henrique
LH
Guerreiro
Daniel
D
Da Silva
Eduardo
E
Ricci-Junior
Wendell
W
Girard-Dias
Camile Moreira
CM
Mascarenhas
Mauro
M
Sola-Penna
Kildare
K
Miranda
Luís Maurício T R
LM
Lima
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004655:Emulsions; D005215:Fasting; D006801:Humans; D007279:Injections, Subcutaneous; D058228:Islet Amyloid Polypeptide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D012995:Solubility
D001067:Appetite Depressants; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004655:Emulsions; D058228:Islet Amyloid Polypeptide; D011091:Polyesters; C016240:polycaprolactone