In vivo and in vitro characteristics for insulin-loaded PLA microparticles prepared by w/o/w solvent evaporation method with electrolytes in the continuous phase

Abstract

Insulin-loaded poly(lactide) (PLA) microparticles were successfully prepared by 6% w/v PLA in the organic phase, 10% w/v PVP and varied types of 5%w/v electrolytes in the continuous phase, by using a water-in-oil-in-water emulsion/solvent extraction technique. Addition of electrolytes such as NaCl, CaCl₂ into the external phase significantly improved insulin entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency, with microparticle yield 81.2%, trapping efficiencies 49%, insulin-loading level 5.5% w/w and mean particle size 14.8 µm. The distribution (%) of insulin on the PLA microparticles surface, outer layer and core were 8, 37 and 43%, respectively. The cumulative release of insulin had an upper limit of ∼24% of the insulin load at 24 days. A steady release rate was 0.5 µg insulin/mg microparticles/day of insulin release maintained for 24 days. Total protein-leaking amount was reduced after addition of electrolytes in the continuous aqueous phase. Rabbit glucose levels were evaluated after subcutaneous 20 mg insulin-loaded PLA microparticles or PLA blank microparticles. Study results show that the insulin-loaded PLA microparticles significantly reduced the glucose level than PLA blank microparticles. The insulin-loaded PLA microparticles, physicochemical characterization data and the animal result obtained in this study may be relevant in optimizing the PLA microparticle formulation incorporation and delivery insulin carriers.

Keywords: :

• Insulin
• poly(lactide)
• microparticles
• solvent evaporation method
• electrolytes