Liposomal paclitaxel induces apoptosis, cell death, inhibition of migration capacity and antitumoral activity in ovarian cancer.

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX.

Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis.

To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Immunogenic cell death induction by the Pacli/Dox combination was assessed .

Physical and biological effects of paclitaxel encapsulation on disteraroylphosphatidylethanolamine-polyethyleneglycol polymeric micelles.

Simple size observations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) polymeric micelles (PM) with different compositions including or not paclitaxel (PTX) are unable to evidence changes on the nanocarrier structure. In such system a detailed characterization using highly sensitive techniques such as X-ray scattering and asymmetric flow field flow fractionation coupled to multi-angle laser light scattering and dynamic light scattering (AF4-MALS-DLS) is mandatory to observe effects that take place by the addition of PTX and/or more lipid-polymer at PM, leading to complex changes on the structure of micelles, as well as in their supramolecular organization. SAXS and AF4-MALS-DLS suggested that PM can be found in the medium separately and highly organized, forming clusters of PM in the latter case.

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes.

Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties.

Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells.

Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice.

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis.

Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering.

The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides available, among them, Tecnethium-99m (Tc). Tc is readily conjugated with nanoparticles using chelating agents, such as diethylenetriaminepentaacetic acid (DTPA).

Long-Circulating and pH-Sensitive Liposome Preparation Trapping a Radiotracer for Inflammation Site Detection.

Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity.

Synthesis of nitroaromatic compounds as potential anticancer agents.

Twenty-seven nitrated and non-nitrated compounds have been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines (IC50 < 8.5 μM).

Evaluation of antitumor activity and development of solid lipid nanoparticles of metronidazole analogue.

Nitroheterocyclic compounds have received considerable interest as hypoxia-selective cytotoxins (HSC) for cancer treatment. In the present study, we investigated antitumor activity of an iodide analogue of metronidazole, 1-(2-iodoethyl)-2-methyl-5-nitroimidazole (MTZ-I), using Swiss mice bearing solid Ehrlich tumor. MTZ-I showed potent anti-cancer activity at a dose of 40 mg/kg.

Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles.

This work aims to develop solid lipid nanoparticles (SLNs) loaded with retinoic acid (RA) to evaluate the influence of two lipophilic amines, stearylamine (SA) and benethamine (BA), and one hydrophilic, triethylamine (TA), on drug-encapsulation efficiency (EE) and cytotoxicity in cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without amine) to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively.

New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles.

This work aimed to develop solid lipid nanoparticles (SLNs) loaded with doxorubicin evaluating the influence of docosahexaenoic acid (DHA), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency (EE). The SLN were characterized for size, zeta potential, entrapment efficiency (EE) and drug release. Studies of in vitro antitumor activity and cellular uptake were also conducted.

Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor.

Cisplatin (CDDP) is one of the most active cytotoxic agents commonly used in the treatment of peritoneal carcinomatosis. The disadvantages of its clinical use are systemic side-effects, such as nephrotoxicity and myelotoxicity. Long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) were developed by our research group aiming to promote the release of CDDP near the tumor as well as decreasing toxicity.

Amphotericin B-loaded nanocarriers for topical treatment of cutaneous leishmaniasis: development, characterization, and in vitro skin permeation studies.

Topical treatment of cutaneous leishmaniasis represents an exciting alternative for reducing toxicity associated with parenteral administration of conventional amphotericin B. This work aims to develop and to characterize amphotericin B-loaded new carriers and to investigate their potential for topical delivery by conducting permeation studies with pig ear skin in comparison with marketed formulations. Among other formulations, nanoemulsions were developed and characterized for size, encapsulation efficiency, and zeta potential.

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.

Biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice.

Cisplatin (CDDP) is one of the most active cytotoxic agents and has been widely used in the treatment of peritoneal carcinomatosis by the intraperitoneal (i.p.) route.

Liposomes radiolabeled with (159)Gd: 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.

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.

Bombesin derivative radiolabeled with technetium-99m as agent for tumor identification.

A bombesin derivative was successfully radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle and tumor-to-blood ratios.

Study of the pilot production process of long-circulating and pH-sensitive liposomes containing cisplatin.

Long-circulating and pH-sensitive liposomes, containing cisplatin (SpHL-CDDP), have been developed as an alternative aimed at avoiding severe side effects as well as the appearance of resistance, which can limit the use of free cisplatin. However, physical (i.e.

A novel D-glucose derivative radiolabeled with technetium-99m: synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor.

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio.

Synthesis and biological evaluation of technetium-labeled D-glucose-MAG3 derivative as agent for tumor diagnosis.

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio and moderate tumor-to-blood ratio.

Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration.

Aims: The objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice.

Main Methods: After single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD(50) was calculated. Blood samples were collected for biochemical and hematological analysis.

Antischistosomal activity of aminoalkanethiols, aminoalkanethiosulfuric acids and the corresponding disulfides.

This paper discusses the development of a series of sulfur-containing compounds that show an interesting in vivo activity against infection by Schistosoma mansoni. These substances include the aminoalkanethiols, aminoalkanethiosulfuric acids and aminoalkyl disulfides, among others. Although the aminoethanethiols and their disulfide derivatives have presented a relatively high toxicity for the host animal, the aminoalkanethiosulfuric acids have a low toxicity and a high specificity for the adult female S.

Effect of cationic lipid composition on properties of oligonucleotide/emulsion complexes: Physico-chemical and release studies.

This paper describes the influence of cationic lipid composition on physico-chemical properties of complexes formed between oligonucleotides (ON) and cationic emulsions. Formulations containing medium chain triglycerides, egg lecithin, increasing amounts of either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and water were prepared by a spontaneous emulsification procedure. ON adsorption on emulsions was evidenced by the inversion of the zeta-potential, the increase in droplet size, and the morphology of the oil droplet examined through transmission electron microscopy.