Background/Objectives: Lipoxins, particularly Lipoxin A4 (LXA4), are endogenous lipid mediators with potent anti-inflammatory and pro-resolving properties, making them promising candidates for the treatment of inflammatory and neurodegenerative disorders. However, their therapeutic application is limited by poor stability and bioavailability. This study aimed to develop and characterize nanomicelles encapsulating LXA4 (nano-lipoxin A4) to improve its pharmacological efficacy against Alzheimer’s disease (AD), a neurodegenerative condition marked by chronic inflammation and beta-amyloid (Aβ) accumulation. Methods: Nano-lipoxin A4 was synthesized using Pluronic F-127 as a carrier and characterized in terms of morphology, physicochemical stability, and in vitro activity against Aβ fibrils. Dissociation of Aβ fibrils was assessed via Thioflavin-T fluorescence assays and transmission electron microscopy. In vivo biodistribution and pharmacokinetic profiles were evaluated using technetium-99m-labeled nano-lipoxin A4 in rodent models. Hepatic biochemical parameters were also measured to assess potential systemic effects. Results: In vitro studies demonstrated that nano-lipoxin A4 effectively dissociated Aβ fibrils at concentrations of 50 nM and 112 nM. Electron microscopy confirmed the disruption of fibrillar structures. In vivo imaging revealed predominant accumulation in the liver and spleen, consistent with reticuloendothelial system uptake. Pharmacokinetic analysis showed a prolonged half-life (63.95 h) and low clearance rate (0.001509 L/h), indicating sustained systemic presence. Biochemical assays revealed elevated liver enzyme levels, suggestive of increased hepatic metabolism or potential hepatotoxicity. Conclusions: Nano-lipoxin A4 exhibits significant therapeutic potential for Alzheimer’s disease through effective modulation of Aβ pathology and favorable pharmacokinetic characteristics. However, the elevation in liver enzymes necessitates further investigation into systemic safety to support clinical translation.
This study investigates the potential of arimoclomol-loaded nanomicelles for the treatment of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as their anti-inflammatory properties. Arimoclomol, a coinducer of heat shock proteins (HSPs), has shown clinical promise in mitigating protein misfolding, a hallmark of these diseases. In this work, arimoclomol nanomicelles significantly reduced the aggregation of β-amyloid (Aβ1-42) and α-synuclein (α-syn), key pathological proteins in Alzheimer's and Parkinson's. Additionally, the nanomicelles demonstrated potent anti-inflammatory effects, reducing leukocyte and neutrophil counts in an acute inflammation model. These results suggest that arimoclomol nanomicelles could enhance clinical outcomes by targeting both neurodegenerative and inflammatory processes, offering a promising therapeutic strategy for long-term disease management.
17 May 2023 in Colloids and Surfaces B: Biointerfaces
Lamivudine is a synthetic nucleoside analogue to cytosine with a modified sugar moiety. It has potent action against Human Immunodeficiency Virus and chronic hepatitis. Recently, studies have also shown that lamivudine (3TC) can induce apoptosis in cancer cells and inhibit their proliferation, including breast cancer. We prepared polymeric nanoparticles using the double emulsification technique to incorporate polycaprolactone (PCL) as the polymer and lamivudine as the active compound. The nanoparticles were characterized by atomic force microscopy and dynamic light scattering. Then we carried out a full set of in vitro and in vivo analyses, including measurement of cytotoxicity, radiolabeling, biodistribution and biochemistry. The results showed the formation of 273 nm spherical nanoparticles with monodisperse behavior (PDI = 0.052). The radiolabeling with 99mTc demonstrated the feasibility of the direct radiolabeling process. The cytotoxicity corroborated the potential against the triple-negative breast cancer line (MDA-MB-231). The biodistribution assay revealed high uptake in the liver, small and large intestines and bladder, besides the presence of nanoparticles in the urine. The in vivo biochemistry analysis showed alterations in some enzyme levels, including: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma GT (GGT), creatinine (CRE), amylase (MAS), lactate dehydrogenase pyruvate (LDH-P) and glucose (GLU). Finally, we performed theoretical studies of molecular docking, molecular dynamics and interactions between lamivudine and key proteins regulating necroptosis, including epidermal growth factor receptor (EGFR), receptor-interacting protein kinase 1 (RIPK1), and receptor-interacting protein kinase 3 (RIPK3). Theoretical results showed lamivudine's adaptability to the binding sites of these proteins, with potential for optimization to enhance hydrophobic interactions and binding affinity. The findings demonstrated the efficacy of lamivudine against breast cancer cells, and the need to better understand the interplay of nanosystems with biochemical parameters.
Using recycled materials is increasingly recognized as a crucial strategy in today’s global context. The production of glass on a global scale, estimated at approximately 209 million tons annually, underscores the urgent necessity to identify alternative applications for this material. In this milieu, the adoption of recycled glass for applications conducive to health emerges as a significant opportunity, offering dual advantages: mitigating the global surplus of glass and enhancing public health outcomes. In the realm of diseases, oncology, and hepatocellular carcinoma stand out due to their extensive costs and detrimental impact on health. Consequently, this research has been directed toward developing, comprehensively characterization, and in vivo assessment of Ho (Ho-166) holmium-166 doped glass microspheres derived from recycled glass. The findings confirmed the successful formation of these microspheres, marked by a high degree of holmium doping. Moreover, the studies revealed a significant accumulation of the microspheres in the liver, alongside a lack of toxicological effects. Collectively, these results strongly support the potential of recycled glass as a valuable resource for fabricating holmium-doped glass microspheres, offering a promising avenue for liver cancer treatment.