Polycaprolactone Antimony Nanoparticles as Drug Delivery System for Leishmaniasis.

BACKGROUND: Leishmaniasis is a neglected disease endemic in tropical and subtropical areas, with an incidence about 1.6 million cases/year. The first-line treatment of this disease is pentavalent antimony, and the second-line are pentamidine and amphotericin B. All the treatments available cause severe side effects and often have difficulty in accessing parasites within infected cells. STUDY QUESTION: This study aimed to determine if the use of nanoparticles loaded with meglumine antimoniate could reach and targeting infected organs with leishmaniasis, reducing the dosage used and promoting less adverse effects. STUDY DESIGN: This study was performed comparing the meglumine nanoparticle in two experimental groups. The first one healthy mice and the second one inducted mice (leishmaniasis). MEASURES AND OUTCOMES: The nanoparticles loaded with meglumine antimoniate (nanoantimony) were prepared by double-emulsion solvent evaporation method and showed a size of about 150-200 nm. BALB/c mice infected or not with Leishmania amazonensis (cutaneous leishmaniasis model) or Leishmania infantum (visceral leishmaniasis model) was used to access the biodistribution of nanoantimony and meglumine antimoniate labeled with technetium-99m. RESULTS: The biodistribution profiles showed a preferential targeting of the nanoparticles to the liver, spleen, and lungs. Because these are the main organs infected, the nanoparticle may be used for this purpose. The results for cutaneous leishmaniasis showed a low uptake by the lesion (infected region). CONCLUSIONS: The results demonstrated the potential use of these nanoparticles to improve the efficacy of meglumine antimoniate in the treatment of visceral leishmaniasis, indicating their potential as an alternative therapeutic strategy for leishmaniasis infections.

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.

Nanoradiopharmaceuticals for breast cancer imaging: development, characterization, and imaging in inducted animals.

Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200-500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of -14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.

Development of novel nanoparticle for bone cancer.

Bone metastasis is responsible for up to 99% of bone tumors. As no cure has yet to be discovered, available treatments simply strive to improve quality of life. One of such treatments is the use of EDTMP (ethylenediamine-tetramethylenephosphonic acid) labeled with Samarium-153, which has been shown to improve survival in 70-80% of patients treated. A major disadvantage of this radiopharmaceutical is its superficial delivery, resulting in the need for multiple doses. The current work describes novel polymeric nanoparticles of EDTMP and evaluation of their biodistribution in vivo. Nanoparticles were prepared using a double emulsion-solvent evaporation method and characterized by AFM (atomic force microscopy). Nanoparticles (200-500 nm) were then labeled with Technetium-99m for biodistribution analysis in healthy Wistar rats. Polymeric nanoparticles of EDTMP were observed to accumulate at bone tissue for long periods of time (150 min), resulting in prolonged release of EDTMP at the target site. This finding suggests that this novel pharmaceutical formulation of EDTMP provides better targeted delivery than free EDTMP and may be a more optimal treatment for management of bone metastasis pain.

Radiolabelled nanohydroxyapatite with 99mTc: perspectives to nanoradiopharmaceuticals construction.

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.

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.