OpenNano最新文献

Introduction

Recently, bis(arylmethylidene)acetone drugs known as C5-curcumin, were acknowledged for their potent biological effects as a neoteric synthetic alternative to curcumin effectively used to treat many diseases.

Methods

In this study, new polymeric emulsified nanoparticles (PENS) carrying biodegradable polycaprolactone (PCL) polymer moieties within their framework were developed as promising carriers for a modern synthesized bis(arylmethylidene)acetone “(1E,4E)-1,5-di(thiophen-2-yl) penta-1,4dien-3-one” (TPO) with improved bioavailability. Such systems were evaluated by studying their; encapsulation efficiency, release behavior, physicochemical evaluations, TEM and SEM measurements and cytotoxicity, besides the in-vitro and in-vivo biological studies screening.

Results

The results revealed high encapsulation efficiency ranging between 99.31± 2.15 and 99.55 ± 2.03 %, and a sustained release behavior for up to 24 h with nanosized particle size. TPO emulsified nanoparticles (TPO-ENPs) showed effective antimicrobial activity against Candida albicans and Aspergillus brasiliensis as well as antioxidant efficacy with a higher scavenging activity of 177.6μg TE/ mg against free radicals of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) relatively to the control drug. F1’ and F2’ TPO-ENPs were safe on Vero-cells and proved a significant reduction of hepatocellular alterations and serum ALT levels in control groups.

Conclusion

In conclusion, these novel synthesized TPO-ENPs showed pronounced efficacy as antimicrobial/ antioxidant/ anti-inflammatory/ analgesic/ hepatoprotective therapeutic vehicles.

Nucleic acid therapeutics are rapidly expanding because of recent advancements in production and purification. This class of therapeutics may change the field of disease treatment and personalized medicine since it can cure diseases. However, drug delivery systems are crucial for these therapeutics to fulfill their potential. Liposomes have long been considered ideal platforms for systemic drugs delivery. Considering the development in cancer therapeutics, this work emphases on the current advancements in liposomes’ Nano-formulations, functionalization, and design and how it has been applied to nucleic acid therapeutics. Accordingly, this review covers the literature that deals with liposomes in nucleic acid therapy.

Various health agencies, such as the European Medical Agency (EMA), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO), timely cited the upsurge of antibiotic resistance as a severe threat to the public health and global economy. Importantly, there is a rise in nosocomial infections among covid-19 patients and in-hospitalized patients with the delineating disorder. Most of nosocomial infections are related to the bacteria residing in biofilm, which are commonly formed on material surfaces. In biofilms, microcolonies of various bacteria live in syntropy; therefore, their infections require a higher antibiotic dosage or cocktail of broad-spectrum antibiotics, aggravating the severity of antibiotic resistance. Notably, the lack of intrinsic antibacterial properties in commercial-grade materials desires to develop newer functionalized materials to prevent biofilm formation on their surfaces. To devise newer strategies, materials prepared at the nanoscale demonstrated reasonable antibacterial properties or enhanced the activity of antimicrobial agents (that are encapsulated/chemically functionalized onto the material surface). In this manuscript, we compiled such nanosized materials, specifying their role in targeting specific strains of bacteria. We also enlisted the examples of nanomaterials, nanodevice, nanomachines, nano-camouflaging, and nano-antibiotics for bactericidal activity and their possible clinical implications.

Curcumin (CUR) is a bioactive compound that has been proposed for the treatment of various neurodegenerative diseases. However, its use is limited due to its low solubility in aqueous media and chemical instability under physiological conditions. Herein, we propose a strategy to overcome these limitations by using PAMAM dendrimers of generation 4.5 (DG4.5). Using a combination of biophysical techniques together with in vitro models, we demonstrate that CUR-DG4.5 complexes: (i) increased the solubility and stability of CUR via internalization into dendrimer's pockets and interaction with terminal carboxylic groups; (ii) showed in vitro biocompatibility and increased CUR uptake; (iii) presented DPPH radical scavenging activity and in vitro inhibition of H₂O₂-induced stress; and (iv) interfere with α-synuclein aggregation. In conclusion, this work lays the foundation to use curcumin-loaded PAMAM dendrimers of generation 4.5 as nanodrugs capable of reducing oxidative stress and inhibiting α-synuclein aggregation to treat synucleinopathies.

This work aimed to prepare ketoconazole-loaded ethosomes and binary ethosomes to improve its skin delivery and antifungal efficacy. A 3² factorial design was used to optimize the ethosomes and formulate ketoconazole-loaded binary ethosomes. Ethosomes and binary ethosomes were evaluated for particle size, polydispersity index, zeta potential, percent drug entrapment efficiency, drug release, skin permeation and deposition and antifungal efficacy. The ethosomes particle size ranged from 78.99±16.72 to 321.53±10.41 nm and decreased by increasing phospholipid and ethanol concentrations. The polydispersity index values were in the range of 0.17±0.01 to 0.49 ± 0.04. The percent drug entrapment efficiency ranged from 36.09±2.66 to 95.89±0.19 and increased by increasing phospholipid concentration while ethanol concentration had the opposite effect. The binary ethosomes had smaller size but similar drug entrapment efficiency and zeta potential compared with the ethosomes. They had significantly higher percent drug release (∼96%) and permeation (∼95%) through rat skin compared with the ethosomes (93% and 90%, respectively). Binary ethosomes and ethosomes had, respectively 1.9 and 1.8-fold higher drug skin permeation and 5.3- and 5.6-fold higher drug deposition in the epidermis/dermis compared with the drug suspension. The antifungal efficacy of the drug-loaded ethosomes and binary ethosomes were similar to the drug hydroalcoholic solution. Collectively, these results confirm the potential of these nanocarriers to enhance drug efficacy given their small size, sustained drug release and enhanced skin permeability.

The synthesis of covered nanoparticles provides new properties to the materials for biomedical applications. This fully applies to iron oxide nanoparticles. The research aim was to study features of the magnetite nanoparticles synthesized by electron beam technology as well as to investigate their functionalization and cytotoxicity. Nanoparticle characteristics were determined by standard methods. Cytotoxiciy of nanoparticles was studied using erythrocyte model. It was shown that the original magnetite nanoparticles in the sodium chloride matrix can be functionalized with polyvinylpyrrolidone and ethylmethylhydroxypyridine succinate, an antioxidant. All investigated nanoparticles were non-toxic for erythrocytes at concentrations up to 100 μg Fe/ml. At 100-200 μg Fe/ml, they increased the amount of cells expressing phosphatidylserine on the outer membrane, the count of pathological forms of erythrocytes and hemolysis. These phenomena were less pronounced if the nanosystem included the antioxidant. Therefore, magnetite nanoparticles can be obtained by electron beam technology and functionalized to form non-toxic nanosystems.

Conventional anti-cancer drugs, including doxorubicin, are associated with high toxicity and non-specific distribution in the body which results in a cascade of side effects. Cancer cells can utilize autophagy to promote tolerance to the stress induced by anti-cancer agents; this may be the major cause of drug resistance in advanced tumors. Owing to the molecular dynamism of cancer cells, targeting the pro-apoptotic survival pathways such as autophagy may increase the effectiveness of existing therapeutic agents at lower concentrations, thereby reducing the side effects of such agents. SAR405 is an inhibitor of autophagy activity due to its molecular interactions within the ATP binding site; however, it suffers from extracellular premature degradation and poor cellular uptake. Conversely, chitosan nanoparticles are considered biologically degradable, non-toxic, and biocompatible drug delivery agents that can be used to minimize the side effects of conventional therapeutic agents whilst increasing their intracellular uptake. In this study, a binary therapeutic strategy for the enhancement of the efficacy of doxorubicin while simultaneously inhibiting autophagy via a nano-mediated delivery system is reported. Autophagic inhibition was achieved via the improvement of SAR405 cellular uptake using SAR405-loaded chitosan nanoparticles. The synthesized nanoparticles were subsequently characterized for parameters of hydrodynamic diameter and polydispersity, while encapsulation and drug loading efficiencies were determined. Morphological characterization of the nanoparticles was elucidated using electron microscopy, and the cytotoxicity of the SAR405-loaded chitosan nanoparticles in combination treatments with doxorubicin was assessed through MTT and Annexin-v apoptosis assays. Autophagy progression through autophagosome formation was also evaluated using CYTO-ID staining. Following encapsulation, the size of the SAR405-loaded chitosan nanoparticles significantly increased from 54 nm to 161 nm at 10 µM SAR405 concentration, while the polydispersity index increased from 0.11 to 0.31 denoting presence of both encapsulated and unencapsulated moieties. When A549 lung cancer cells were treated with the IC₅₀ values of doxorubicin in combination with SAR405-encapsulated CNP, an approximately 47% more reduction in cell viability was observed via the Annexin V-FITC/PI assay compared to using doxorubicin alone. Inhibition of autophagy was also detected in cells treated with SAR405 delivered using the nanoparticle system and was thought to be the primary reason towards a decrease in the resistance of the cancer cells to doxorubicin and thus increased its efficacy at lower concentrations. Therefore, this study has demonstrated a potential way of targeting cancer cell survival pathways that can be considered an effective way of increasing the efficacy of chemotherapeutic drugs.

Pioglitazone is a type 2 diabetes drug encapsulated in polymeric nanoparticles using solvent evaporation techniques. In this study, the drug-polymer ratio (A), stirring speed (B), and stirring time (C) were three process parameters that were optimized using a three-factor, three-level Central Composite design. Entrapment efficiency, Pioglitazone content, and particle size were assessed as responses to the three dependent variables. The independent and dependent variables were associated using mathematical equations and response surface graphs. The optimization model of entrapment efficiency of about 61.7 %, Pioglitazone content of 12.33 %, and particle size of 323 nm with A, B, and C levels of 1:2, 3000 rpm, and 20 min respectively. The expected values of the optimized technique and the observed responses exhibited good agreement. Morphological examinations, Fourier transforms infrared spectroscopy, and in-vitro drug release tests were used to characterize the produced nanoparticle. The synthesized nanoparticles demonstrated effective sustained drug release. In an in vivo system, the synthesized nanoparticles demonstrated enhanced drug bioavailability. Pioglitazone-loaded nanoparticle treatment of streptozotocin-induced diabetic rats significantly decreased blood glucose levels (up to 7 days) to normal levels (up to 6 hours) when compared to the native drug-treated group. The in vivo toxicity study of the nanoparticles in albino rats failed to detect any appreciable alterations in hematological, biochemical, or behavioral tests. Since Pioglitazone is used to treat type 2 diabetes mellitus, the created system may help achieve a regulated release of the medication, which could assist in lowering dosage frequency and improve patient compliance.

Delivering drugs to tumors using nanoparticles (NPs) has shown promising potential in promoting targeted drug delivery of antineoplastic agents to enhance their efficiency while reducing the associated systemic toxicity. This review highlights the different types of NPs and the physiological characteristics of the tumor microenvironment (TME), and the mechanisms undertaken to safely deliver drugs to specific lesions. We review the principles and latest developments in the field of targeted NPs designed to target tumor vasculature compared to those designed to target cancer cells and their correlation with the TME. We discuss the advantages and limitations of each targeted drug delivery mechanism and future directions aiming to maximize their potential.