Ralph Santos-Oliveira

Biodistribution of nanoparticles: Initial considerations

Nanotechnology is attracting increasing attention worldwide. This study was made use of modern technology to decipher most of the intriguing biological aspects of nanoparticles. Labeling with technetium-99m ((99m)Tc) of six nanoparticles using different compositions and formulations, as well as complete biodistribution studies in mice was done. The results showed that the behaviors of nanoparticles were very different from each other. Mesoporous silica showed a high affinity for lung tissue, whereas polymeric nanoparticles were rapidly recognized and metabolized by the liver. The six nanoparticles showed different renal clearance times, suggesting that their area mechanisms of action were related to interaction and solubility. The labeling process in all samples showed similar results (all >99%). Biodistribution was demonstrated to be important for the study of nanoparticles, and could be used to predict the possible mechanism of action of nanoparticles.

Radiolabelled nanohydroxyapatite with 99mTc: perspectives to nanoradiopharmaceuticals construction.

Abstract The use of nanoparticles is under intense investigation. The possible advantages proposed by these systems are very impressive and the results may be quite schemer. In this scenario, the association of nanoparticles with radioactive materials (radionuclide) may be the most important step since the discovery of radioactive for nuclear medicine and radiopharmacy, especially for cancer targeting and therapy. In this study, we developed radiolabelled nanoparticles of hydroxyapatite with technetium 99m for bone cancer imaging. The results demonstrated that it is possible to label nanoparticles of hydroxyapatite, and due to its physicochemical properties is possible to develop nano-radiopharmaceutical for bone imaging.

Aptamer-based nanoparticles for cancer targeting.

Abstract Background: The use of mesoporous silica for cancer targeting is increasing rapidly. The association between rigid model of nanoparticles such as mesoporous silica and biological compounds with affinity for oncological diseases is a very promising drug targeting system nowadays. Methods: In this study, we used the mesoporous silica (SBA-15) associated with aptamer (functionalized for the tumor marker MUC-1). Results: The results obtained in the characterization were quite interesting and demonstrated that the silica produced were very uniform and with a size range of 50–100 nm. Thus, the results of cytotoxicity demonstrated that there is no cytotoxicity related to the nanoparticle. Conclusion: We conclude that although further studies are required, the nanoparticle mesoporous silica model loaded with aptamer is very functional and its use can be widespread for other application especially in nuclear medicine.

Anti-MUC1 nano-aptamers for triple-negative breast cancer imaging by single-photon emission computed tomography in inducted animals: initial considerations

The early and specific detection of tumors remains a barrier in oncology, especially in cases such as the triple-negative breast cancer (TNBC). To address this gap, aptamers have found an important application in the recognition of tumor biomarkers such as mucin 1 (MUC1). However, there are still some difficulties in the use of aptamer, as their rapid biological clearance makes their use as drugs limited. In this study, the anti-MUC1 aptamer was used as a drug delivery system (DDS) for a radioactive polymeric nanoparticle (NP) in the imaging of TNBCs. Thus, poly(lactic-co-glycolic acid) NPs loaded with the anti-MUC1 aptamer and labeled with technetium-99m were used for a biodistribution study and imaging of TNBC. The results confirmed that the NP was successfully obtained, with a mean size of 262 nm, according to the dynamic light scattering data. The biodistribution assay in induced animal models with TNBC showed that although there was a high capture by intestine (>30%), the DDS developed had a high tumor uptake (5%) and with great in vivo imaging properties, corroborating the possibility of use of this DDS as an imaging drug for TNBC.

Topical Application Effect of the Isolectin Hydrogel (Cramoll 1,4) on Second-Degree Burns: Experimental Model

This study aimed at evaluating the use of hydrogel isolectin in the treatment of second-degree burns. Twenty male rats were randomly divided into two groups (G1 = treatment with hydrogel containing 100 μg/mL Cramoll 1,4 and G2 = Control, hydrogel). After 7, 14, 21, 28, and 35 days, animals were euthanized. On the 7th day, G1 showed intense exudates, necrosis and edema. On the 14th day, G1 showed tissue reepithelialization and moderate autolysis. On the 21st day, G1 showed intense fibroblastic proliferation, presence of dense collagen, and moderate fibrosis. On the 28th day, G1 showed complete tissue epithelialization. On the 35th day, G1 showed modeled dense collagen. The significant wound contraction was initiated from day, 14 in the G1. There were no significant differences in biochemical and hematological parameters analyzed. These results extend the potential of therapeutic applications for Cramoll 1,4 in the treatment of thermal burns.

Radiopharmaceuticals drug interactions: a critical review

Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.

In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals

The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way.

Comparison of biodistribution profile of monoclonal antibodies nanoparticles and aptamers in rats with breast cancer

Abstract The use of monoclonal antibodies and aptamers is growing every single day, as the use of nanoparticle systems. Although most of the products are under investigation, there are a few commercialized products available at the market, for human consume. In this study, we have compared three formulations (aptamer anti-MUC1, monoclonal antibody – Trastuzumab and monoclonal antibodies nanoparticles – PLA/PVA/MMT trastuzumab) to identify their profile as also to understand their behavior into an alive biological system. In this direction the radiolabeling of the products were done and they were all tested in animals (in vivo) in two conditions: healthy rats and breast cancer induced animals. The results showed that the nanoparticle has the better biodistribution profile, followed by the aptamer. We conclude that more studies and a global effort to elucidate the biological behavior of drugs and especially nano-drugs are necessary.

Drug metabolism: Comparison of biodistribution profile of holmium in three different compositions in healthy Wistar rats.

Radioisotope holmium is a candidate to be used in cancer treatment and diagnosis. There are different holmium salts and they present distinct solubility and consequently different biodistribution profiles. In this work, we aimed to evaluate the biodistribution profiles of two holmium salts (chloride and sulfate) and holmium nanoparticles (oxide) through an in vivo biodistribution assay using animal model. Samples were labeled with technetium-99m and administered in Wistar rats by retro-orbital route. Holmium chloride is highly soluble in water and it was quickly filtered by the kidneys while holmium sulfate that presents lower solubility in water was mainly found in the liver and the spleen. However, both the salts showed a similar biodistribution profile. On the other hand, holmium oxide showed a very different biodistribution profile since it seemed to interact with all organs. Due to its particle size range (approximately 100nm) it was not intensively filtered by the kidneys being found in high quantities in many organs, for this reason its use as a nanoradiopharmaceutical could be promising in the oncology field.

Development of nanoradiopharmaceuticals by labeling polymer nanoparticles with tc-99m.

Nanomedicine is considered as the future of modern medicine. Hence, serious global efforts are being made for the development of nanopharmaceuticals. Among all the nanopharmaceuticals developed so far, radiopharmaceuticals constitute only a very small portion, as noted in the published literature. The procedures for development of nanoradiopharmaceuticals are complex. In this paper we discuss the results of a research directed at developing nanoradiopharmaceuticals based on three different types of nanopharmaceuticals as alternative drug delivery systems.