ABSTRACT
ABSTRACT Sustained release systems for therapeutic proteins have been widely studied targeting to improve the action of these drugs. Molecular entrapping of proteins is particularly challenging due to their conformational instability. We have developed a micro-structured poly-epsilon-caprolactone (PCL) particle system loaded with human insulin using a simple double-emulsion w/o/w method followed by solvent evaporation method. This formulation is comprised by spheric-shaped microparticles with average size of 10 micrometers. In vitro release showed a biphasic behavior such as a rapid release with about 50% of drug delivered within 2 hours and a sustained phase for up to 48 h. The subcutaneous administration of microencapsulated insulin showed a biphasic effect on glycemia in streptozotocin-induced diabetic mice, compatible with short and intermediate-acting behaviors, with first transition peak at about 2 h and the second phase exerting effect for up to 48h after s.c. administration. This study reveals that a simplified double-emulsion system results in biocompatible human-insulin-loaded PCL microparticles that might be used for further development of optimized sustained release formulations of insulin to be used in the restoration of hormonal levels.
Subject(s)
Animals , Male , Female , Mice , Insulin/analysis , Pharmaceutical Preparations/administration & dosage , Microscopy, Electron/statistics & numerical data , Diabetes Mellitus/prevention & control , Particulate Matter/pharmacology , Drug Liberation/physiology , Hypoglycemic Agents/pharmacologyABSTRACT
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.
