Abstract 2772: Biodistribution and pharmacokinetics of RGD grafted PLGA nanoparticles after radiolabling with 99mTC on tumor bearing rat model

Abstract

Abstract Aim of the studies was to investigate influence of targeting (RGD) moiety on biodistribution of Docetaxel (DC) encapsulated PLGA-NPs in tumor bearing rats. Nanoparticles (Nps) were prepared by emulsification technique. RGD-conjugation was done by carbodiimide method. NPs were characterized for size, zeta potential, drug encapsulation efficiency, RGDfk content and drug interaction with PLGA and RGDfk. Radiolabeling of DC, DC loaded nanoparticles (PLGA-DC-NPs) and DC loaded and RGD grafted nanoparticles (PLGA-DC-RGDfk-NPs) formulations were achieved using stannous chloride as reducing agent (Babbar et al., 1991). The quality control of labeling efficiency was performed by ascending TLC using silica gel coated fiber sheets using acetone as a mobile phase. Stability of the Tc-99m labeled DC and formulations was determined in vitro in rabbit serum, normal saline by ascending TLC technique. Tc-99m labeled DC solution; PLGA-DC-NPs & PLGA-DC-RGDfk-NPs were administered i.v. via the tail vein at a dose of 20mg/kg body weight into the tumor bearing rats weighing about 250-300 gm. The blood samples were collected at 0.5, 1,2,4,6, 12 and 24 hrs post injection into anticoagulant. The different organs were isolated and homogenized at 1, 2, 4 and 24hrs. Radioactivities in the samples were measured using gamma counter. Pharmacokinetic parameters were calculated using Kinetica 4.4. Gamma scintigraphy study was done at 4, 24 and 48hrs. The drug loaded Nps were found to be in nano size with 72.5% drug entrapment efficiency and negative zeta potential. 99m Tc labeling efficiency was found to be high with stability up to 24hr. Calculated plasma AUC(0→24), AUC(0→∞), MRT, and t1/2 of DC solution and NPs were found to be in increasing order of PLGA-DC-RGDfk-NPs>PLGA-DC-NPs > DC solution. Which reveals the long circulation and slow clearance of drug loaded targeted NPs compared to non RGD grafted NPs and drug solution. Gamma scintigraphy studies reveals that the drug solution was rapidly eliminates from the tumor site as well as from the body. The DC-PLGA-RGDfk-NPs accumulate in the tumor very fast and show significantly high radioactivity than the PLGA-DC-NPs and drug solution alone for longer period of time. DC loaded Nps were prepared successfully exhibited in nano size with excellent resdispersibility. Labeling of DC and DC Nps with 99mTc resulted in stable complexes. The improved Pharmacokinetic and biodistribution data suggest the slow clearance of PLGA-DC-RGDfk with compared to PLGA-DC-NPs and drug solution from the body. Gamma schintigraphy studies demonstrated the high accumulation of RGD grafted Nps in the tumor for longer period of time. These findings of the studies are suggestive of drug localization in breast cancer site after grafting of Nps with RGD in animals and more extensive studies are necessary to develop a product suited for clinical use for better outcome then present chemotherapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2772.