Breaking barriers: The potential of nanosystems in antituberculosis therapy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to pose a significant threat to global health. The resilience of TB is amplified by a myriad of physical, biological, and biopharmaceutical barriers that challenge conventional therapeutic approaches. This review navigates the intricate landscape of TB treatment, from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression. Amidst these challenges, traditional therapies often fail, contending with inconsistent bioavailability, prolonged treatment regimens, and socioeconomic burdens. Nanoscale Drug Delivery Systems (NDDSs) emerge as a promising beacon, ready to overcome these barriers, offering better drug targeting and improved patient adherence. Through a critical approach, we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo. This review advocates for the intensification of research in NDDSs, heralding their potential to reshape the contours of global TB treatment strategies.

Engineering resveratrol-loaded chitosan nanoparticles for potential use against Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a microorganism directly linked to severe clinical conditions affecting the stomach. The virulence factors and its ability to form biofilms increase resistance to conventional antibiotics, growing the need for new substances and strategies for the treatment of H. pylori infection. The trans-resveratrol (RESV), a bioactive polyphenol from natural sources, has a potential activity against this gastric pathogen. Here, Chitosan nanoparticles (NP) containing RESV (RESV-NP) were developed for H. pylori management. The RESV-NP were prepared using the ionic gelation method and characterized by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and, Cryogenic Transmission Electron Microscopy (Cryo - TEM). The encapsulation efficiency (EE) and in vitro release rate of RESV were quantified using high-performance liquid chromatography (HPLC). RESV-NP performance against H. pylori was evaluated by the quantification of the minimum inhibitory/bactericidal concentrations (MIC/MBC), time to kill, alterations in H. pylori morphology in its planktonic form, effects against H. pylori biofilm and in an in vitro infection model. RESV-NP cytotoxicity was evaluated against AGS and MKN-74 cell lines and by hemolysis assay. Acute toxicity was tested using Galleria mellonella model assays. RESV-NP showed a spherical shape, size of 145.3 ± 24.7 nm, polydispersity index (PDI) of 0.28 ± 0.008, and zeta potential (ZP) of + 16.9 ± 1.81 mV in DLS, while particle concentration was 3.12 x 1011 NP/mL (NTA). RESV-NP EE was 72 %, with full release within the first 5 min. In microbiological assays, RESV-NP presented a MIC/MBC of 3.9 µg/mL, a time to kill of 24 h for complete eradication of H. pylori. At a concentration of 2xMIC (7.8 µg/mL), RESV-NP completely eradicated the H. pylori biofilm, and in an in vitro infection model, RESV-NP (4xMIC - 15.6 µg/mL) showed a significant decrease in bacterial load (1 Log10CFU/mL) when compared to the H. pylori J99 control. In addition, they did not demonstrate a toxic character at MIC concentration for both cell lines. The use of the RESV-NP with mucoadhesion profile is an interesting strategy for oral administration of substances targeting gastric disorders, linked to H. pylori infections.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

Macrophage Cell Membrane Coating on Piperine-Loaded MIL-100(Fe) Nanoparticles for Breast Cancer Treatment.

Piperine (PIP), a compound found in Piper longum, has shown promise as a potential chemotherapeutic agent for breast cancer. However, its inherent toxicity has limited its application. To overcome this challenge, researchers have developed PIP@MIL-100(Fe), an organic metal-organic framework (MOF) that encapsulates PIP for breast cancer treatment. Nanotechnology offers further treatment options, including the modification of nanostructures with macrophage membranes (MM) to enhance the evasion of the immune system. In this study, the researchers aimed to evaluate the potential of MM-coated MOFs encapsulated with PIP for breast cancer treatment. They successfully synthesized MM@PIP@MIL-100(Fe) through impregnation synthesis. The presence of MM coating on the MOF surface was confirmed through SDS-PAGE analysis, which revealed distinct protein bands. Transmission electron microscopy (TEM) images demonstrated the existence of a PIP@MIL-100(Fe) core with a diameter of around 50 nm, surrounded by an outer lipid bilayer layer measuring approximately 10 nm in thickness. Furthermore, the researchers evaluated the cytotoxicity indices of the nanoparticles against various breast cancer cell lines, including MCF-7, BT-549, SKBR-3, and MDA. The results demonstrated that the MOFs exhibited between 4 and 17 times higher cytotoxicity (IC50) in all four cell lines compared to free PIP (IC50 = 193.67 ± 0.30 µM). These findings suggest that MM@PIP@MIL-100(Fe) holds potential as an effective treatment for breast cancer. The study's outcomes highlight the potential of utilizing MM-coated MOFs encapsulated with PIP as an innovative approach for breast cancer therapy, offering improved cytotoxicity compared to free PIP alone. Further research and development are warranted to explore the clinical translation and optimize the efficacy and safety of this treatment strategy.

Development, characterization and in vitro cytotoxicity of kaempferol-loaded nanostructured lipid carriers in glioblastoma multiforme cells.

Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of - 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells.

Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review.

The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Currently this drug is being used in several types of cancer. Rapamycin has been a target of great interest within nanomedicine involving nanostructured systems for drug delivery aiming to increase the bioactivity and bioavailability of this drug. In addition, there is a constant search for analytical methods to identify and quantify this drug. Numerous high-performance liquid chromatography analytical techniques, mass spectrometry and immunoassay techniques have been employed efficiently in an attempt to develop increasingly sensitive analytical methods. Thus, this review sought to bring together current and relevant scientific works involving rapamycin and; besides analytical methods more used for quantification of this molecule.

Oral delivery of micro/nanoparticulate systems based on natural polysaccharides for intestinal diseases therapy: Challenges, advances and future perspectives.

Colon-targeted oral delivery of drugs remains as an appealing and promising approach for the treatment of prevalent intestinal diseases (ID), such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Notwithstanding, there are numerous challenges to effective drug delivery to the colon, which requires the design of advanced strategies. Micro- and nanoparticles have received great attention as colon-targeted delivery platforms due to their reduced size and structural composition that favors the accumulation and/or residence time of drugs at the site of action and/or absorption, contributing to localized therapy. The choice by natural polysaccharides imparts key properties and advantages to the nano-in-microparticulate systems to effective colon-specific oral delivery. This review proposes to discuss the physiological barriers imposed by the gastrointestinal tract (GIT) against oral administration of drugs, as well as pathological factors and challenges of the ID for oral delivery of colon-targeted systems. We then provide an updated progress about polysaccharides-based colon-targeted drug delivery systems, including microparticulate, nanoparticulate and nano-in-microparticulate systems, highlighting their key properties, advantages and limitations to achieving targeted delivery and efficacious therapy within the colon. Lastly, we provide future perspectives, towards advances in the field and clinical translation of colon-targeted oral delivery systems for ID therapy.

Luminescent nanohybrids based on silica and silylated Ru(II)-Yb(III) heterobinuclear complex: new tools for biological media analysis.

Lanthanide (Ln) complexes emitting in the near-infrared (NIR) region have fostered great interest as upcoming optical tags owing to their high spatial and temporal resolution emission as well deeper light penetration in biological tissues for non-invasive monitoring. For use in live-cell imaging, lanthanide complexes with long-wavelength absorption and good brightness are especially critical. Light-harvesting ligands of Ln complexes are typically excited in the ultraviolet region, which in turn trigger simultaneously autofluorescence and long-exposition damage of living systems. The association of d-metalloligands rather than organic chromophores enables the excitation of NIR-emitting Ln complex occurs in the visible region. Taking advantage of the long-lived excited states and intense absorption band in the ultraviolet (UV) to NIR region of Ru(II), we successfully design a dual-emitting (in the visible and NIR region) d-f heterobinuclear complex based on Ru(II) metalloligand and Yb(III) complex. In addition, we developed luminescent nanohybrids by grafting of Ru(II)-Yb(III) heterobinuclear complexes containing silylated ligands on the surface of mesoporous and dense silica matrix. The nanomarkers were successfully applied for imaging of murine melanoma B16-F10 and neonatal human dermal fibroblast HDFn cell cultures by one-photon or two-photon absorption using laser scanning confocal microscopy. Great cellular uptake, low cytotoxicity and the possibility to achieve visible and NIR emission via two-photons excitation show that the nanohybrids are remarkable markers for in vitro and a potential tool for in vivo applications.