원문정보
초록
영어
Complex systems of protein and chargeable polymer have been investigated to keep protein stability in PLGA microsphere because the complex protects protein denaturation induced by an acidic environment and water/organic interface. Our group reported a potential of chodroitin sulfate (CSA) as a polymer additive to form ionic complex with positively charged proteins in long-term protein delivery[1]. However, CSA in neutral pH can not make a complex with protein
having lower pI value. Thus, the polymer applied at low pH (2-3) to make complex with protein having lower pI value such as insulin and exenatide. Here,
insulin (pI=5.30-5.35) was employed as a model protein. CSA and insulin complex constructed nano-sized particles with 100 to 400 nm at pH 3.0. Zeta potential result showed that above 1:0.5 feeding ratio of insulin and CsA, net charge on the surface of the complex is approached at 0. Based on this preliminary study, poly(lactide-co-glycolide) (PLGA) microspheres including
Ins/CsA complexes was prepared by a multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of insulin released from PLGA microspheres revealed nearly zero-order kinetics. Cicular dicholoism (CD) spectra of released insulin indicated that the insulin in PLGA microspheres with the complex preserved its stability for 20 days, while insulin in no complex system partially
is denaturated. This result means that complex system with CSA is useful for long term delivery of protein (having a lower pI value) at lower pH.