Biodistribution study and identification of inflammatory sites using nanocapsules labeled with (99m)Tc-HMPAO.

PURPOSE: To evaluate the ability of polymeric nanocapsules (NCs) radiolabeled with technetium-99m D,L-hexamethylpropyleneamine oxime (Tc-HMPAO) to identify inflammatory process in an experimental model. METHODS: NCs were prepared by interfacial deposition of preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by a solvent displacement. The size and homogeneity, and zeta potential of the NC preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. The NCs radiolabeled with Tc-HMPAO were administered intravenously to Wistar male rats bearing a focal inflammation induced by subplantar injection of carrageenan in the right foot. At preestablished time intervals, the animals were anesthetized, tissues were removed and radioactivity was determined using an automatic scintillation apparatus. RESULTS: The average diameter calculated by photon correlation spectroscopy varied from 216 to 323 nm. The biodistribution studies showed a greater uptake of the PEG surface-modified Tc-HMPAO-NC by the inflamed paws when compared with the respective controls. There was no significant difference in the uptake of conventional Tc-HMPAO-NC and of free Tc-HMPAO by inflamed and control paws. These results indicate that the PLA-PEG Tc-NC showed a higher uptake in inflammation compared with free complex and may be useful as a radiotracer to identify these foci.

Physicochemical characterization and study of in vitro interactions of pH-sensitive liposomes with the complement system.

Complement activation is an important step in the acceleration of liposome clearance. The anaphylatoxins released following complement activation may motivate a wide variety of physiologic changes. We performed physicochemical characterization and in vitro studies of the interaction of complement system with both noncirculating and long-circulating pH-sensitive and nonpH-sensitive liposomes. The liposomes were characterized by diameter, zeta potential, and atomic force microscopy (AFM). The study of liposome interactions with complement system was conducted using hemolytic assay in rat serum. All liposomes presented a similar mean diameter (between 99.8 and 124.3 nm). The zeta potential was negative in all liposome preparations, except in liposomes modified with aminopoly (ethyleneglycol) 2000-distearoylphosphatidylethanolamine (aPEG(2000)-DSPE), which presented positive zeta potential. Atomic force microscopy images showed that non-long-circulating pH-sensitive liposomes are prone to vesicles aggregation. Non-pH-sensitive liposomes complement system activates, while pH-sensitive liposomes showed to be poor complement activators in rat serum.

Biodistribution study and identification of inflammation sites using 99mTc-labelled stealth pH-sensitive liposomes.

PURPOSE: To investigate the biodistribution and the ability of stealth pH-sensitive liposomes radiolabelled with 99mTc to identify inflammatory regions in a rat focal inflammation model. METHODS: Preformed glutathione-containing stealth pH-sensitive liposomes were labelled with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). The 99mTc-HMPAO radiolabelled stealth pH-sensitive liposomes (99mTc-SpHL) were administered intravenously in Wistar male rats with inflammation induced by injection subplantar of carrageenan in the right foot. At pre-established time intervals the animals were anaesthetized and tissues were removed and analysed for 99mTc content using an automatic scintillation apparatus. Scintigraphic imaging was also performed after 2, 4 and 8 h of intravenous injection of 99mTc-SpHL. RESULTS: The 99mTc-SpHL was significantly taken up by the spleen (19.21+/-2.98%ID/g at 30 min post-injection). Low radioactivity levels were found in the liver, lungs, and kidney. Moreover, the 99mTc-SpHL uptake was significantly higher in the inflamed foot when compared to the respective control (0.386+/-0.059 and 0.215+/-0.018%ID/g at 2 h post-injection, respectively). As early as 30 min after administration of 99mTc-SpHL, the focus of inflammation could be visualized scintigraphically. The value of the inflammatory and non-inflammatory site radioactivity counting ratio was greater than 5. CONCLUSION: This result indicates that the 99mTc-SpHL presents a high tropism for inflammatory regions and may be useful as a radiopharmaceutical to identify these foci.