In vivo evaluation of mebendazole and Ran GTPase inhibition in breast cancer model system.

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.

Doxorubicin conjugates: a practical approach for its cardiotoxicity alleviation.

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects. AREAS COVERED: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting. EXPERT OPINION: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.

Meta-analysis of nano-phytosomes: unleashing the potential of plant-derived compounds for advancing cancer therapy.

Nano-phytosomes are considered as an efficient drug delivery system for phytochemicals. Phytosomes enhance stability and significantly improves phytochemicals bioavailability and therapeutic efficacy. Thorough meta-analysis of 93 articles, phytochemical versus phytosomes size, charge, polydispersity index (PDI) and IC50 values were investigated. Multivariate Analysis of Covariance revealed significant phytochemicals type effects, even when accounting for cancer cell type and phospholipid type as covariates. Least Significant Difference (LSD) post hoc tests described unique attributes among various phytosomes. Flavonoid-based phytosomes exhibited larger particle sizes than others. In contrast, terpenoid-based phytosomes displayed significantly lower charges. Flavonoids demonstrated higher poly dispersity index (PDI) values than alkaloids and polyphenols. Alkaloids exhibited more extensive PDI values, while polyphenols had lower PDI values than terpenoids. Furthermore, flavonoid-containing nanoparticles exhibited higher IC50 values than terpenoids. In conclusion, nano-phytosomes offer promising prospects for revolutionising drug delivery methodologies and advancing the development of innovative therapeutic solutions in the domain of cancer therapy.

Magnetic iron oxide-based nanozymes: from synthesis to application.

Iron oxide nanozymes (IONzymes) are a class of magnetic nanoparticles that mimic the enzymatic activity of natural enzymes. These particles have received significant attention in recent years due to their unique properties, such as high stability, tunable magnetic responsiveness, and ability to act as biocatalysts for various chemical reactions. In this review, we aim to provide an overview of the production methods of magnetic nanozymes, including chemical, physical, and biological synthesis. The structure and design of magnetic nanozymes are also discussed in detail, as well as their applications in various fields such as biomedicine and environmental science. The results of various studies and the latest advances in the field of magnetic nanozymes are also discussed. This review provides valuable insights into the current state of magnetic nanozymes and highlights their potential for further development and application in various fields.

In vitro dissolution equivalence of Jordanian sildenafil generics via validated, stability-indicating HPLC method.

This study was conducted to compare dissolution profiles of four Jordanian registered sildenafil (SDF) products to the originator. Dissolution samples were analyzed utilizing a validated and stability-indicating HPLC method in human plasma. Validation was performed for specificity, linearity, limit of detection, lower limit of quantification, precision, trueness and stability. SDF was extracted from plasma samples using liquid-liquid extraction. The analysis was performed utilizing isocratic elution on C18 column with 1.0 ml/min flow rate. The regression value was ∼0.999 over 3 days with drug recovery between 86.6 to 89.8%with 10 ng/ml lower limit of quantitation. This method displayed a good selectivity of SDF with improved stability under various conditions. The method was used for SDF quantification in dissolution medium. Similarity factors for local products varied according to the used mediums, but all SDF local products passed the dissolution in vitro test since all of them showed a released of >85% after 60 min at the dissolution mediums.

Preparation, characterization and in vitro evaluation of 5-fluorouracil loaded into chitosan-acacia gum nanoparticles.

Aim: In this study, we prepared, characterized and in vitro evaluated a 5-fluorouracil (5-FU)-loaded chitosan-acacia gum nanoparticles. Methods: Nanoparticles were characterized for their size, charge, morphology and encapsulation efficiency (EE%) followed by cellular investigations against HT-29 colon cancer cell line. Results: The nanoparticles exhibited a spherical morphological size with 94.42% EE%. Free 5-FU showed a fast and fully cumulative release after 6 h while 5-FU loaded into CS-AG NPs showed good entrapment and slow, prolonged 5-FU release even after 24 h. Enhanced IC50 for the 5-FU loaded NPs compared with free 5-FU against HT-29 colon cancer cell line was reported with high selectivity compared with normal fibroblast cells. Conclusion: 5-FU loaded NPs is promising nano-therapy against colon cancer.

Dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer.

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques. EXPERT OPINION: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.

The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia.

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of the BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 and 22. This fusion gives rise to the oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The Abl protein intricately regulates the cell cycle by phosphorylating protein tyrosine residues through diverse signaling pathways. In CML, the BCR-ABL fusion protein disrupts the first exon of Abl, leading to sustained activation of tyrosine kinase and resistance to deactivation mechanisms. Pharmacological interventions, such as imatinib, effectively target BCR-ABL's tyrosine kinase activity by binding near the active site, disrupting ATP binding, and inhibiting downstream protein phosphorylation. Nevertheless, the emergence of resistance, often attributed to cap structure mutations, poses a challenge to imatinib efficacy. Current research endeavours are directed towards overcoming resistance and investigating innovative therapeutic strategies. This article offers a comprehensive analysis of the structural attributes of BCR-ABL, emphasizing its pivotal role as a biomarker and therapeutic target in CML. It underscores the imperative for ongoing research to refine treatment modalities and enhance overall outcomes in managing CML.

Liposome bilayer stability: emphasis on cholesterol and its alternatives.

Liposomes are spherical lipidic nanocarriers composed of natural or synthetic phospholipids with a hydrophobic bilayer and aqueous core, which are arranged into a polar head and a long hydrophobic tail, forming an amphipathic nano/micro-particle. Despite numerous liposomal applications, their use encounters many challenges related to the physicochemical properties strongly affected by their constituents, colloidal stability, and interactions with the biological environment. This review aims to provide a perspective and a clear idea about the main factors that regulate the liposomes' colloidal and bilayer stability, emphasising the roles of cholesterol and its possible alternatives. Moreover, this review will analyse strategies that offer possible approaches to provide more stable in vitro and in vivo liposomes with enhanced drug release and encapsulation efficiencies.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Aptasensors: employing molecular probes for precise medical diagnostics and drug monitoring.

Accurate detection and monitoring of therapeutic drug levels are vital for effective patient care and treatment management. Aptamers, composed of single-stranded DNA or RNA molecules, are integral components of biosensors designed for both qualitative and quantitative detection of biological samples. Aptasensors play crucial roles in target identification, validation, detection of drug-target interactions and screening potential of drug candidates. This review focuses on the pivotal role of aptasensors in early disease detection, particularly in identifying biomarkers associated with various diseases such as cancer, infectious diseases and cardiovascular disorders. Aptasensors have demonstrated exceptional potential in enhancing disease diagnostics and monitoring therapeutic drug levels. Aptamer-based biosensors represent a transformative technology in the field of healthcare, enabling precise diagnostics, drug monitoring and disease detection.

Development and validation of reversed-phase-HPLC method for simultaneous quantification of fulvestrant and disulfiram in liposomes.

This study aims to develop and validate an HPLC technique for the determination of fulvestrant and disulfiram in liposomes. Encapsulation of both drugs into liposomes may improve their anticancer potential. Validation was performed following the International Conference on Harmonization guidelines for specificity, linearity, limit of detection, limit of quantification, precision, accuracy and robustness. Method specificity displayed no interference and linearity over 25-200 and 12.5-100 µg/ml for fulvestrant and disulfiram, respectively. Precision and accuracy exhibited a low relative standard deviation (<1.70%) and appropriate recovery. The validated method could be designated as a proper method for the simultaneous determination of fulvestrant and disulfiram in liposomes. The liposomes displayed 148.5 ± 5.1 nm size. The encapsulation efficiencies were 73.52 and 50.50% for fulvestrant and disulfiram, respectively.

Preparation, Characterization, and Anticancer Activity of PEGylated Nano Liposomal Loaded with Rutin against Human Carcinoma Cells (HT-29).

The abstract discusses the development of rutin-loaded nanoliposomes and their anti-colorectal cancer activity against human carcinoma cells (HT-29). The study characterizes the nanoliposomes using the thin-film hydration method and analyzes their size, charge, and polydispersity index. The encapsulation efficiency and drug loading ability of rutin at different concentrations were investigated. The nanoliposomes were found to be stable for up to one month at 4 °C and showed sustained drug release for up to 24 h. The anti-cancer activity of the rutin-loaded nanoliposomes was found to be concentration-dependent and significantly improved compared to free rutin. PEGylated nanoliposomes with rutin (1.8 mg/ml) showed the highest encapsulation efficiency and drug loading ability, along with improved selectivity against cancer cells. Overall, the study provides important insights into the potential use of rutin-loaded nanoliposomes for the treatment of colorectal cancer.

Review on PLGA Polymer Based Nanoparticles with Antimicrobial Properties and Their Application in Various Medical Conditions or Infections.

The rise in the resistance to antibiotics is due to their inappropriate use and the use of a broad spectrum of antibiotics. This has also contributed to the development of multidrug-resistant microorganisms, and due to the unavailability of suitable new drugs for treatments, it is difficult to control. Hence, there is a need for the development of new novel, target-specific antimicrobials. Nanotechnology, involving the synthesis of nanoparticles, may be one of the best options, as it can be manipulated by using physicochemical properties to develop intelligent NPs with desired properties. NPs, because of their unique properties, can deliver drugs to specific targets and release them in a sustained fashion. The chance of developing resistance is very low. Polymeric nanoparticles are solid colloids synthesized using either natural or synthetic polymers. These polymers are used as carriers of drugs to deliver them to the targets. NPs, synthesized using poly-lactic acid (PLA) or the copolymer of lactic and glycolic acid (PLGA), are used in the delivery of controlled drug release, as they are biodegradable, biocompatible and have been approved by the USFDA. In this article, we will be reviewing the synthesis of PLGA-based nanoparticles encapsulated or loaded with antibiotics, natural products, or metal ions and their antibacterial potential in various medical applications.

Impact of exosome therapy on pancreatic cancer and its progression.

Pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. There are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. Exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. They have been verified to be potential biomarkers for pancreatic cancer management. Studying the role of exosomes in pancreatic cancer is substantial. Exosomes are secreted by most eukaryotic cells and participated in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long non-coding RNA, circular RNA, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal miRNAs as possible pancreatic cancer biomarkers. Finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed.

Development of Pegylated Nano-Phytosome Formulation with Oleuropein and Rutin to Compare Anti-Colonic Cancer Activity with Olea Europaea Leaves Extract.

Olive leaf extract is a valuable source of phenolic compounds; primarily, oleuropein (major component) and rutin. This natural olive leaf extract has potential use as a therapeutic agent for cancer treatment. However, its clinical application is hindered by poor pharmacokinetics and low stability. To overcome these limitations, this study aimed to enhance the anticancer activity and stability of oleuropein and rutin by loading them into PEGylated Nano-phytosomes. The developed PEGylated Nano-phytosomes exhibited favorable characteristics in terms of size, charge, and stability. Notably, the anticolonic cancer activity of the Pegylated Nano-phytosomes loaded with oleuropein (IC50=0.14 µM) and rutin (IC50=0.44 µM) surpassed that of pure oleuropein and rutin alone. This outcome highlights the advantageous impact of Nano-phytosomes to augment the anticancer potential of oleuropein and rutin. These results present a promising pathway for the future development of oleuropein and rutin Nano-phytosomes as effective options for passive tumor-targeted therapy, given their improved stability and efficacy.

Formulating co-loaded nanoliposomes with gallic acid and quercetin for enhanced cancer therapy.

Cancer is considered one of the top global causes of death. Natural products have been used in oncology medicine either in crude form or by utilizing isolated secondary metabolites. Biologically active phytomolecules such as gallic acid and quercetin have confirmed antioxidant, anti-bacterial, and neoplastic properties. There is an agreement that microorganisms could mediate oncogenesis or alter the immune system. This research project aims to develop a novel formulation of co-loaded gallic acid and quercetin into nanoliposomes and investigate the efficacy of the free and combined agents against multiple cancerous cell lines and bacterial strains. Thin-film hydration technique was adopted to synthesize the nanocarriers. Particle characteristics were measured using a Zetasizer. The morphology of nanoliposomes was examined by scanning electron microscopy, Encapsulation efficiency and drug loading were evaluated using High-Performance Liquid Chromatography. Cytotoxicity was determined against Breast Cancer Cells MCF-7, Human Carcinoma Cells HT-29, and A549 Lung Cancer Cells. The antibacterial activities were evaluated against Acinetobacter baumannii, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Therapeutic formulas were categorized into groups: free gallic acid, free quercetin, free-mix, and their nano-counterparts. Findings revealed that drug loading capacity was 0.204 for the mix formula compared to 0.092 and 0.68 for free gallic acid and quercetin, respectively. Regarding the Zeta potential, the mix formula showed more amphiphilic charge than the free quercetin and free gallic acid formulas (P-values 0.003 and 0.002 receptively). On the contrary, no significant difference in polydispersity indices was reported. Lung cancerous cells were the most affected by the treatments. The best estimated IC50 values were observed in breast and lung cancer lines for the nano-gallic acid and co-loaded particles. The nano-quercetin formula exhibited the least cytotoxicity with an IC50 value of ≥200 µg/mL in both breast (MCF-7) and colorectal adenocarcinoma cell lines (HT-29) with no activity against the lung. A remarkable improvement in the efficacy of quercetin was measured after mixing it with gallic acid against the breast and lungs. The tested therapeutic agents exhibited antimicrobial activity against gram-positive bacteria. Nano-liposomes can either enhance or reduce the cytotoxicity activity of active compounds depending on the physical and chemical properties of drug-loaded and type of cancer cells.

Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.

PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes. PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS). CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.

Impact of nanotechnology on the oral delivery of phyto-bioactive compounds.

Nanotechnology is an advanced field that has remarkable nutraceutical and food applications. Phyto-bioactive compounds (PBCs) play critical roles in promoting health and disease treatment. However, PBCs generally encounter several limitations that delay their widespread application. For example, most PBCs have low aqueous solubility, poor biostability, poor bioavailability, and a lack of target specificity. Moreover, the high concentrations of effective PBC doses also limit their application. As a result, encapsulating PBCs into an appropriate nanocarrier may increase their solubility and biostability and protect them from premature degradation. Moreover, nanoencapsulation could improve absorption and prolong circulation with a high opportunity for targeted delivery that may decrease unwanted toxicity. This review addresses the main parameters, variables, and barriers that control and affect oral PBC delivery. Moreover, this review discusses the potential role of biocompatible and biodegradable nanocarriers in improving the water solubility, chemical stability, bioavailability, and specificity/selectivity of PBCs.