Preparation and evaluation of tacrolimus-loaded nanoparticles for lymphatic delivery.

In an effort to improve lymphatic targeting efficiency and reduce the toxicity of tacrolimus, the emulsification-diffusion method was used to load the drug into nanoparticles (NP). Poly(lactide-co-glycolide) (PLGA) and PLGA surface-modified with poly(ethylene glycol) (PEG) were used as polymers. Mean particle size and drug encapsulation efficiency of PLGA were 218+/-51nm and 60.0+/-1.2% and for PEG-PLGA NP were 220+/-33nm and 60.3+/-2.0%. NP were characterized by thermal analyzer and X-ray diffractometry (XRD), and their shapes were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In vitro release profiles were affected by the pH of dissolution media. The prepared NP and commercial product of tacrolimus (Prograf) inj.) were intravenously administered to rats to compare their pharmacokinetic characteristics and lymphatic targeting efficiency. The area under the whole blood concentration-time curve (AUC), mean residence time (MRT), and total clearance (CL(t)) of PEG-PLGA NP were significantly different (P<0.05) compared with those of Prograf inj., and lymphatic targeting efficiencies of both NP formulations at the mesenteric lymph node significantly increased (P<0.05). These results showed that the prepared tacrolimus-loaded NP are good possible candidates as a lymphatic delivery system of tacrolimus. Copyright (c) 2009 Elsevier B.V. All rights reserved.