APPLICATION OF BIODEGRADABLE NANOPARTICLES IN LIVER TARGETING OF TACROLIMUS
- Conference date: 4–5 November 2010
- Location: Little Rock, Arkansas
Tacrolimus is a potent immunosuppressant used in liver transplantation to avoid graft rejection. Tacrolimus has a narrow therapeutic index and variable pharmacokinetics, making dose adjustment and therapeutic drug monitoring a complicated task. Increasing the occurrence of adverse effects, especially nephrotoxicity are another concerns. In graft rejection, antigen presentation occurs in the graft and lymphatics. Therefore, by targeting tacrolimus to the liver and spleen, graft survival could be achieved with a decrease in nephrotoxicity. Poly(lactide) tacrolimus nanoparticles (PLA‐TAC‐NP) were formulated and characterized with the aim of targeting tacrolimus to the liver and spleen and therefore decreasing its nephrotoxicity. To evaluate the targeting efficiency of PLA‐TAC‐NP, rats were divided into two groups. They were intravenously injected either PLA‐TAC‐NP or free tacrolimus. At assigned time intervals, blood, liver, spleen and kidney samples were collected from each rat. Drug extraction and HPLC analysis were used to evaluate tacrolimus tissue distribution and consequently the targeting efficiency of the prepared PLA‐TAC‐NP. PLA‐TAC‐NP proved their success in targeting liver and spleen, by showing significantly higher drug amounts compared to the rats injected with free tacrolimus. PLA‐TAC‐NP increased tacrolimus concentration in the liver 24 fold and in the spleen 1.94 fold whereas tacrolimus concentration in the kidneys decreased by 7.12 fold. Transmission electron microscopy (TEM) was used to examine a liver section, obtained from a rat that has received PLA‐TAC‐NP. TEM images showed PLA‐TAC‐NP in a Kupffer cell and in the liver sinusoids. Therefore, PLA‐TAC‐NP are promising drug delivery systems for achieving localized immunosuppression and minimizing nephrotoxicity in liver transplant patients.
- Transmission electron microscopy
- Drug delivery
- Medical imaging
MOST READ THIS MONTH
MOST CITED THIS MONTH
Article metrics loading...