Daniel Crístian Ferreira Soares

Boron nitride nanotubes radiolabeled with 99mTc: Preparation, physicochemical characterization, biodistribution study, and scintigraphic imaging in Swiss mice

In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.

Liposomes radiolabeled with 159Gd: In vitro antitumoral activity, biodistribution study and scintigraphic image in Ehrlich tumor bearing mice

PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the Gd-DTPA-BMA complex were prepared and radiolabeled by neutron activation. The radiolabeled liposomes presented significant in vitro cytotoxic activity against Ehrlich tumor cells when compared with controls. The biodistribution profile of these liposomes and free (159)Gd-DTPA-BMA were studied in mice bearing a previously-developed solid Ehrlich tumor. The results demonstrated an important uptake of the formulations by the tumor tissue, with a tissue/blood partition coefficient (Kp) 3.88 and 14.16 times higher than that of the free complex for pH-sensitive PEG-coated and PEG-folate-coated liposomes containing the (159)Gd-DTPA-BMA complex, respectively. Both formulations accumulated in the liver and spleen, thereby revealing some difficulty in escaping the action of the MPS cells. The formulation without folate presented a lower renal uptake, which is desirable in patients with chronic renal failure due to the potential risk of nephrogenic systemic fibrosis (NFS). The scintigraphic study revealed that the target/non-target ratio is always greater than three for pH-sensitive PEG-coated liposome formulations and above nine for pH-sensitive PEG-folate-coated liposome formulations. The results obtained in this study demonstrated that the formulations employed can be considered to be a potential alternative for the treatment of cancer, including patients with chronic renal failure.

Boron nitride nanotubes coated with organic hydrophilic agents: Stability and cytocompatibility studies

In the present study, Boron Nitride Nanotubes (BNNTs) were synthesized and functionalized with organic hydrophilic agents constituted by glucosamine (GA), polyethylene glycol (PEG)1000, and chitosan (CH) forming new singular systems. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their surface charge was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by Transmission Electron Microscopy. The functionalization was evaluated by Thermogravimetry analysis and Fourier Transformer Infrared Spectroscopy. The results showed that BNNTs were successfully obtained and functionalized, reaching a mean size and dispersity deemed adequate for in vitro studies. The in vitro stability tests also revealed a good adhesion of functionalized agents on BNNT surfaces. Finally, the in vitro cytocompatibility of functionalized BNNTs against MCR-5 cells was evaluated, and the results revealed that none of the different functionalization agents disturbed the propagation of normal cells up to the concentration of 50 μg/mL. Furthermore, in this concentration, no significantly chromosomal or morphologic alterations or increase in ROS (Reactive Oxygen Species) could be observed. Thus, findings from the present study reveal an important stability and cytocompatibility of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures.

Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery

The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery.

Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification

Long-circulating and pH-sensitive liposomes trapping (99m)Tc-HYNIC-βAla-bombesin((7-14)) (aSpHL-(99m)Tc-BBN((7-14))) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor-bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL-(99m)Tc-BBN((7-14)) could be considered as a potential agent for tumor diagnosis.

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing 159Gd-DTPA-BMA in Ehrlich tumor bearing mice

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹⁵⁹Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.

Liposomes radiolabeled with 159Gd-DTPA-BMA: preparation, physicochemical characterization, release profile and in vitro cytotoxic evaluation.

The present work describes the preparation, labeling, physicochemical characterization, and in vitro cytotoxic evaluation of long circulating pH-sensitive liposomes containing (159)Gd-DTPA-BMA. These liposomes were successfully obtained and submitted to neutron irradiation for gadolinium labeling. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by atomic force microscopy. The stability and release profiles of Gd-DTPA-BMA in the liposomes were determined in vitro in Dubelcos Modified Eagles Medium and rat serum at 70%. The results showed that liposomes remained physically stable after 8 h of irradiation and presented a low release profile of its content in two different biological mediums. The formulation of liposomes containing (159)Gd and its respective controls were evaluated by in vitro cytotoxicity against tumor cells RT2. The results showed increased cytotoxic activity of approximately 1170 fold in relation to free Gd-DTPA-BMA.

Mesoporous silica SBA-16 functionalized with alkoxysilane groups: preparation, characterization, and release profile study

A mesoporous material sphere based on silica, SBA-16, was chemically modified with alkoxysilane using two different solvents: methanol and toluene. The influence of the chemical modification of the matrix on the release rate of a model drug was also studied. The structural characteristics of the materials were evaluated by small-angle X-ray diffraction, N2 adsorption, and transmission electron microscopy. The functionalization of the matrix was evaluated using thermal analysis, FTIR spectroscopy, 13C and 29Si solid-state nuclear magnetic resonance, and elemental analysis, CHN. The results show that alkoxysilane groups have been chemically bonded to silicon atoms on the surface of cubic Im3m mesoporous silica. The influence of the release rate of atenolol molecules from chemically modified mesoporous SBA-16 could be identified, since significant differences could be observed among the release patterns of the different materials.

Salvinia auriculata : aquatic bioindicator studied by instrumental neutron activation analysis (INAA).

Through instrumental neutron activation analysis (INAA) the elemental chemical composition of Salvinia auriculata and Ouro Preto city public water was determined. Elements Ce, Th, Cr, Hf, Sb, Sc, Rb, Fe, Zn, Co, Au, La and Br were quantified. High chromium concentration was determined in this plant. But, chromium was determined only in low concentrations in the water. The results indicate the great capacity of this plant to absorb and accumulate inorganic elements.

Pentacyclic triterpenes from branches of Maytenus robusta and in vitro cytotoxic property against 4T1 cancer cells

Dois novos friedelanos, 1 e 2, e cinco triterpenos pentaciclicos conhecidos foram isolados dos galhos de Maytenus robusta. Suas estruturas quimicas foram identificadas como 3,16-dioxo-29hidroxifriedelano (1), 3-oxo-16b,29-di-hidroxifriedelano (2), 3-oxofriedelano (3), 3b-friedelinol (4), 3,16-dioxofriedelano (5), 3-oxo-29-hidroxifriedelano (6) e 3,16-dioxo-12a-hidroxifriedelano (7). A estrutura e estereoquimica dos triterpenos 1 e 2 foram estabelecidas por infravermelho (IR), ressonância magnetica nuclear (NMR) 1D/2D, espectrometria de massas de alta resolucao com ionizacao quimica a pressao atmosferica (HR-APCIMS) e difracao de raios X de po. A atividade citotoxica in vitro dos triterpenos 1 a 6 foi avaliada frente a celulas de câncer de mama murino. Os triterpenos 1 e 2 apresentaram atividade citotoxica contra celulas 4T1 em baixa concentracao. Two new friedelane-type compounds 1 and 2 and five known pentacyclic triterpenes were isolated from branches of Maytenus robusta. Their structures were identified as 3,16-dioxo29-hydroxyfriedelane (1), 3-oxo-16b,29-dihydroxyfriedelane (2), 3-oxofriedelane (3), 3b-friedelinol (4), 3,16-dioxofriedelane (5), 3-oxo-29-hydroxyfriedelane (6), and 3,16-dioxo12a-hydroxyfriedelane (7). The structures and the stereochemistry of triterpenes 1 and 2 were established through infrared (IR), 1D/2D nuclear magnetic resonance (NMR), high-resolution atmospheric pressure chemical ionization mass spectrometry (HR-APCIMS) spectral data and powder X-ray diffraction. The in vitro cytotoxic property of triterpenes 1 to 6 on 4T1 murine breast cancer cells was evaluated. The triterpenes 1 and 2 showed cytotoxic activity against 4T1 cells at a lower concentration.