Development and assessment of nano drug delivery systems for combined delivery of rosuvastatin and ezetimibe.

Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy. Both rosuvastatin and ezetimibe have low bioavailability which will stand as barrier to decrease cholesterol levels, because of such depictions, formulations of this combined therapy in nanotechnology will be of a great assistance. Our study demonstrated preparations of nanoparticles of this combined therapy, showing their physical characterizations, and examined their behavior in laboratory conditions and vivo habitation. The mean particle size was uniform, polydispersity index and zeta potential of formulations were found to be in the ranges of (0.181-0.72) and (-13.4 to -6.24), respectively. Acceptable limits of entrapment efficiency were affirmed with appearance of spherical and uniform nanoparticles. In vitro testing showed a sustained release of drug exceeded 90% over 24 h. In vivo study revealed an enhanced dissolution and bioavailability from loaded nanoparticles, which was evidenced by calculated pharmacokinetic parameters using triton for hyperlipidemia induction. Stability studies were performed and assured that the formulations are kept the same up to one month. Therefore, nano formulations is a suitable transporter for combined therapy of rosuvastatin and ezetimibe with improvement in their dissolution and bioavailability.

Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats.

Disrupted spermatogenesis and testicular injury are among the devastating outcomes of methotrexate. A major contributor to methotrexate-induced testiculopathy is oxidative damage which triggers apoptosis and altered autophagy responses. Eicosapentaenoic acid ethyl ester (EPA-E) is an antihyperlipidemic derivative of omega-3 fatty acids that exhibited affinity to peroxisome proliferator-activated receptor-γ (PPAR-γ) that possesses both antioxidant and autophagy modulating properties. This is an exploratory study aiming at assessing the effectiveness of EPA-E to alleviate testicular damage induced by methotrexate. The specific exploratory hypothesis of this experiment is: EPA-E administration for 1 week to methotrexate-treated rats reduces testicular damage compared to control rats. As a secondary outcome, we were interested in identifying the implicated mechanism that mediates the action of EPA-E. In adult male Wistar rats, testiculopathy was achieved by a single methotrexate injection (20 mg/kg, ip). Rats received vehicle, EPA-E (0.3 g/kg/day, po) alone or with selective PPAR-γ antagonist (bisphenol A diglycidyl ether, BADGE) at 30 mg/kg/day, ip for 1 week. EPA-E recuperated methotrexate-attenuated serum total testosterone while reduced testicular inflammation and oxidative stress, restoring superoxide dismutase (SOD) while reducing malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Methotrexate-induced testicular apoptosis (caspase-3 and p53) was suppressed upon EPA-E treatment. Besides, EPA-E curbed methotrexate-induced abnormal autophagy by downregulating LC3A/B and beclin-1. Interestingly, BADGE-coadministration reversed EPA-E beneficial actions. Collectively, our findings suggest PPAR-γ role in EPA-E-mediated mitigation of methotrexate-evoked testiculopathy via suppression of oxidative stress, apoptosis, as well as abnormal autophagy. Furthermore, EPA-E could be used as a preventive therapy for some testiculopathies mediated by oxidative stress.

Box Behnken optimization of cubosomes for enhancing the anticancer activity of metformin: Design, characterization, and in-vitro cell proliferation assay on MDA-MB-231 breast and LOVO colon cancer cell lines.

This study aimed to formulate and statistically optimize cubosomal formulations of metformin (MTF) to enhance its breast anticancer activity. A Box Behnken design was employed using Design-Expert® software. The formulation variables were glyceryl monooleate concentration (GMO) w/w%, Pluronic F-127 concentration (PF127) w/w% and Tween 80 concentration w/w% whereas Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. The design expert software was used to perform the process of optimization numerically. X ray diffraction (XRD), Transmission electron microscope (TEM), in-vitro release study, short-term stability study, and in in-vitro cell proliferation assay on the MDA-MB-231 breast cancer and LOVO cancer cell lines were used to validate the optimized cubosomal formulation. The optimized formulation had a composition of 4.35616 (w/w%) GMO, 5 (w/w%) PF127 and 7.444E-6 (w/w%) Tween 80 with a desirability of 0.733. The predicted values for EE%, VS and ZP were 78.0592%, 307.273 nm and - 26.8275 mV, respectively. The validation process carried out on the optimized formula revealed that there were less than a 5% variance from the predicted responses. The XRD thermograms showed that MTF was encapsulated inside the cubosomal vesicles. TEM images of the optimized MTF cubosomal formulation showed spherical non-aggregated nanovesicles. Moreover, it revealed a sustained release profile of MTF in comparison to the MTF solution. Stability studies indicated that optimum cubosomal formulation was stable for thirty days. Cytotoxicity of the optimized cubosomal formulation was enhanced on the MDA-MB-231 breast and LOVO cancer cell lines compared to MTF solution even at lower concentrations. However, it showed superior cytotoxic effect on breast cancer cell line. So, cubosomes could be considered a promising carrier of MTF to treat breast and colon cancers.

miRNAs orchestration of cardiovascular diseases - Particular emphasis on diagnosis, and progression.

MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD.

The potential role of miRNAs in the pathogenesis of cardiovascular diseases - A focus on signaling pathways interplay.

For the past two decades since their discovery, scientists have linked microRNAs (miRNAs) to posttranscriptional regulation of gene expression in critical cardiac physiological and pathological processes. Multiple non-coding RNA species regulate cardiac muscle phenotypes to stabilize cardiac homeostasis. Different cardiac pathological conditions, including arrhythmia, myocardial infarction, and hypertrophy, are modulated by non-coding RNAs in response to stress or other pathological conditions. Besides, miRNAs are implicated in several modulatory signaling pathways of cardiovascular disorders including mitogen-activated protein kinase, nuclear factor kappa beta, protein kinase B (AKT), NOD-like receptor family pyrin domain-containing 3 (NLRP3), Jun N-terminal kinases (JNKs), Toll-like receptors (TLRs) and apoptotic protease-activating factor 1 (Apaf-1)/caspases. This review highlights the potential role of miRNAs as therapeutic targets and updates our understanding of their roles in the processes underlying pathogenic phenotypes of cardiac muscle.

miRNAs as potential game-changers in retinoblastoma: Future clinical and medicinal uses.

Retinoblastoma (RB) is a rare tumor in children, but it is the most common primitive intraocular malignancy in childhood age, especially those below three years old. The RB gene (RB1) undergoes mutations in individuals with RB. Although mortality rates remain high in developing countries, the survival rate for this type of cancer is greater than 95-98% in industrialized countries. However, it is lethal if left untreated, so early diagnosis is essential. As a non-coding RNA, miRNA significantly impacts RB development and treatment resistance because it can control various cellular functions. In this review, we illustrate the recent advances in the role of miRNAs in RB. That includes the clinical importance of miRNAs in RB diagnosis, prognosis, and treatment. Moreover, the regulatory mechanisms of miRNAs in RB and therapeutic interventions are discussed.