Liposomal encapsulation significantly enchances the immunosuppressive effect of tacrolimus in a discordant islet xenotransplant model

Transplantation
Hua YangJames R Wright

Abstract

Encapsulation of tacrolimus (TAC) in a lipid bilayer to form liposome-encapsulated tacrolimus (LTAC) alters the biodistribution profile, half-life, and efficacy in organ allotransplantation models. LTAC has not been applied to either cell transplantation or xenotransplantation. To test the efficacy of LTAC in a discordant islet xenograft model, tilapia (fish) islets were transplanted under the left kidney capsules of streptozotocin-diabetic Balb/c mice. Recipient mice (groups I-VI) were treated with: I, untreated; II, empty liposomes; III, TAC (2 mg/kg/day); IV, TAC (5 mg/kg/day); V, LTAC (2 mg/kg/day); or VI, LTAC (5 mg/kg/day); all treatments were for 35 days or until rejection (i.e., two glucose measurements >200 mg/dl). Graft-bearing kidneys were removed for histology after rejection. Mean graft survival time (mGST) for control groups I and II were 6.7+/-1.4 (n=6) and 7.5+/-1.3 days (n=4), respectively. Daily TAC treatment at 2 mg/kg/d (III) did not prolong graft function (mGST=7.7+/-1.6; n=6) although 5 mg/kg/day (IV) produced minimal prolongation to 12.8+/-4.8 days (n=12). Treatment with LTAC at 2 mg/kg/day (V) significantly prolonged mGST to 26.6+/-4.9 (n=5); however, all recipients rejected during treatment (i.e.,<35 da...Continue Reading

References

Jun 1, 1997·General and Comparative Endocrinology·H YangJ R Wright
Sep 24, 1998·Transplantation Proceedings·S DuttaV C McAlister
Jan 16, 1999·Baillière's Clinical Gastroenterology·K E McColl
Mar 20, 1999·Transplantation Proceedings·V C McAlisterT D Lee
Oct 3, 1999·Xenotransplantation·C J Simeonovic

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Citations

Apr 16, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Quanxing WangXiao-Kang Li

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