TY - JOUR
T1 - Survival prolongation of microencapsulated allogeneic islet by nanosized nordihydroguaiaretic acid
AU - Yang, T. Y.
AU - Chen, J. P.
AU - Ku, K. W.
AU - Fu, S. H.
AU - Hsu, B. R.S.
PY - 2005/5
Y1 - 2005/5
N2 - Immunoisolation such as alginate-poly-L-lysine-alginate (APA) microencapsulation may protect entrapped islet graft cells from destruction by cellular and humoral immunities, but cannot avoid aggregation of macrophages and fibroblasts around microcapsules, which has been known to cause late dysfunction. Nordihydroguaiaretic acid (NDGA) is a lipoxygenase inhibitor that prevents the activation and chemotaxis of macrophages. In this study, we used the dialysis method without surfactant to prepare poly (DL-lactide-co-glycolide) (PLGA) nanoparticles to entrap NDGA. We determined the formulation conditions suitable for sustained release when coencapsulated with the islets. Nanoparticle sizes of 0.2-0.3 μm were suitable for sustained release in electromagnetic driven APA microcapsules. In the toxicity study, we coincubated islets with PLGA-NDGA nanoparticles in vitro for 2 and 4 weeks. The glucose stimulated insulin secretion and insulin contents of islets were not influenced significantly. To test whether nanosized NDGA provides extra protection for APA islets, about 160-200 allogeneic islets of C57BL/6 mice were either encapsulated alone using APA or coencapsulated with PLGA-NDGA. At 2 and 4 weeks after implantation into the peritoneal cavities of healthy BALB/c mice, the intraperitoneal islet grafts were recovered using lavage. Mice that received islets of APA-PLGA-NDGA preparations showed a higher recovery rate of functioning grafts than those that received islets prepared using APA alone (10.1%, n = 4 vs 5.2%, n = 3). In conclusion, nanosized NDGA prolonged the graft survival of APA microencapsulated allogeneic islets.
AB - Immunoisolation such as alginate-poly-L-lysine-alginate (APA) microencapsulation may protect entrapped islet graft cells from destruction by cellular and humoral immunities, but cannot avoid aggregation of macrophages and fibroblasts around microcapsules, which has been known to cause late dysfunction. Nordihydroguaiaretic acid (NDGA) is a lipoxygenase inhibitor that prevents the activation and chemotaxis of macrophages. In this study, we used the dialysis method without surfactant to prepare poly (DL-lactide-co-glycolide) (PLGA) nanoparticles to entrap NDGA. We determined the formulation conditions suitable for sustained release when coencapsulated with the islets. Nanoparticle sizes of 0.2-0.3 μm were suitable for sustained release in electromagnetic driven APA microcapsules. In the toxicity study, we coincubated islets with PLGA-NDGA nanoparticles in vitro for 2 and 4 weeks. The glucose stimulated insulin secretion and insulin contents of islets were not influenced significantly. To test whether nanosized NDGA provides extra protection for APA islets, about 160-200 allogeneic islets of C57BL/6 mice were either encapsulated alone using APA or coencapsulated with PLGA-NDGA. At 2 and 4 weeks after implantation into the peritoneal cavities of healthy BALB/c mice, the intraperitoneal islet grafts were recovered using lavage. Mice that received islets of APA-PLGA-NDGA preparations showed a higher recovery rate of functioning grafts than those that received islets prepared using APA alone (10.1%, n = 4 vs 5.2%, n = 3). In conclusion, nanosized NDGA prolonged the graft survival of APA microencapsulated allogeneic islets.
UR - http://www.scopus.com/inward/record.url?scp=20344408077&partnerID=8YFLogxK
U2 - 10.1016/j.transproceed.2005.03.073
DO - 10.1016/j.transproceed.2005.03.073
M3 - 文章
C2 - 15919479
AN - SCOPUS:20344408077
SN - 0041-1345
VL - 37
SP - 1828
EP - 1829
JO - Transplantation Proceedings
JF - Transplantation Proceedings
IS - 4
ER -