Niosomal Bupropion: Exploring Therapeutic Frontiers through Behavioral Profiling.

Bupropion (Bup) belongs to the norepinephrine-dopamine reuptake inhibitor (NDRI) class and it is the only FDA-approved drug of its class for the treatment of major depressive disorder (MDD), sold under the name of Wellbutrin. Although bupropion is effective in suppressing the symptoms, its regular use and overdose might lead to seizures and liver failure. Thus, we aimed to nanoformulate bupropion onto a niosomal vesicle to improve its efficacy and achieve the same therapeutic effect at lower scheduled doses. A thin film hydration method was adopted to synthesize and optimize Bup entrapped niosomes using three different surfactants of the sorbitan ester series (Span 20, 40, and 60) in combination with cholesterol. The optimization data determined that the niosome formulated with a cholesterol-to-surfactant ratio of 1:1.5 is the most stable system, with the Bup entrapped niosomes containing Span 20 (Bup@N20C) exhibiting minimal in vitro and in vivo toxicity, and demonstrating the sustained release of Bup in artificial cerebrospinal fluid (ACSF). The Bup@N20C formulation showed increased exploration activity and reduced irregular movements in reserpine-induced depression in the adult zebrafish model, suggesting the potential for mood improvement through the suppression of depression-like behavior which was established by statistical analysis and trajectory data. The Bup@N20C-treated group even surpasses the treatment effect of the positive control group and is comparable to the control group. Hence, it can be inferred that niosomal formulations of Bup represent a promising delivery system capable of achieving the brain delivery of the cargo by bypassing the blood-brain barrier facilitated by their small architectural structure.

Association of TIMP2 418 G/C and MMP Gene Polymorphism with Risk of Urinary Cancers: Systematic Review and Meta-analysis.

Aim: The matrix metalloproteinases (MMPs) inhibit tissue inhibitors of metalloproteinases (TIMPs), playing a notable role in various biological processes, and mutations in TIMP2 genes impact a variety of urinary cancers. In this study, we analyze and evaluate the potential involvement of the TIMP2 418 G/C and MMP gene polymorphism in the etiology of urinary cancer. Methodology: For suitable case-control studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. Incorporated into the analysis were case-control or cohort studies that documented the correlation between TIMP2 418 G/C and urological cancers. MetaGenyo served as the tool for conducting the meta-analysis, employing a fixed-effects model. The collective odds ratios, along with their corresponding 95% confidence intervals, were calculated and presented to assess the robustness of the observed associations. Results: A total of seven studies involving controls and cases out of recorded 1265 controls and 1154 cases were analyzed to ascertain the significant association of the TIMP2 gene with urologic cancer. No statistically significant correlation was observed between allelic, recessive, dominant, and overdominant models for the genetic variant under investigation. A 95% confidence interval (CI) and odds ratio (OR) were computed for each model, considering p-values <0.05. The OR and 95% CI for the allelic model were 0.99 and 0.77-1.27, respectively, whereas the respective values were 1.00 and 0.76-1.32 for the recessive model. In the dominant contrast model, OR and 95% CI were 1.09 and 0.62-1.90, while the same were 0.93 and 0.77-1.12 for the overdominant model. A funnel plot was used to reanalyze and detect the results as statically satisfactory. Conclusions: As a result of the data obtained, the TIMP2 gene polymorphism does not correlate statistically with cancer risk. The significance of this finding can only be confirmed using a large population, extensive epidemiological research, a comprehensive survey, and a better understanding of the molecular pathways associated.

Synthetic routes to theranostic applications of carbon-based quantum dots.

Background and Purpose: Modern technologies are making advanced paths to address emerging issues. The development of carbon dots (CDs) technology at a tiny level has been researched to have made impeccable strides in advancing the modern scientific field, especially in nanomedicine. Experimental Approach: Researchers have gained much attention on CDs of their unique properties in the synthesis, easy surface modifications, excellent optical properties, low toxicity, and water solubility. Doping carbon dots with other elements makes them more convenient for their use in the medical sector. Key Results: The manuscript provides a detailed discussion of the two main methods, including the hydrothermal pathway. CDs are synthesized bottom-up by building up molecules at the atomic scale and top-down by transforming large carbon particles into nanoscale dimensions. Conclusion: The present article discussed the role, importance, and recent advancements in the synthesis of CDs, by using various approaches giving importance to the hydrothermal process. Recent investigations, their mechanism, and theranostic applications have also been reported.

Cancer therapy with iRGD as a tumor-penetrating peptide.

One of the primary threats in tumor treatment revolves around the limited ability to penetrate tumor sites, leading to reduced therapeutic effectiveness, which remains a critical concern. Recently gaining importance are novel peptides, namely CRGDK/RGPD/EC (iRGD), that possess enhanced tumor-penetrating and inhibitory properties. These peptides specifically target and penetrate tumors by binding to αvß integrins, namely αvß3 and αvß5, as well as NRP-1 receptors. Remarkably abundant on both the vasculature and tumor cell surfaces, these peptides show promising potential for improving tumor treatment outcomes. As a result, iRGD penetrated deep into the tumor tissues with biological products, contrast agents (imaging agents), antitumor drugs, and immune modulators after co-injecting them with peptides or chemically linked to peptides. The synthesis of iRGD peptides is a relatively straightforward process compared to the synthesis of other traditional peptides, and they significantly improved tumor tissue penetration inhibiting tumor metastasis effectively. Recent studies demonstrate the effectiveness of iRGD-driven dual-targeting chemotherapeutics on cancer cells, and the nanocarriers were modified with iRGD, serving as a favorable delivery strategy of payloads for deeper tumor regions. This review aims to provide an overview to emphasize the recent advancements and advantages of iRGD in treating and imaging various cancers.

Phosphorus-carrying cascade molecules: inner architecture to biomedical applications.

Cascade molecules are nearly uniform-sized macromolecules of small molecules or linear polymer cores built around symmetric branching units. A wide range of biological properties can be achieved with phosphorus-containing dendrimers, depending on their terminal functions, ranging from biomaterials to imaging, drug delivery, and acting as a drug by themselves. This feature article presents significant examples of phosphorus-containing dendrimers used to develop biochips, support cell cultures, carry or deliver biomacromolecules and drugs, bioimaging, and combinational benefits. Because of the thermal stability, ferrocene function, and physical and chemical properties of phosphorus, dendrimers show greater rigidity, mobility, and strength. These dendrimers will be discussed as having a favorable effect on cell growths, especially on neuronal cells, as well as human immune cells like natural killer cells and monocytes, which have a crucial part in preventing cancerous and viral infections. Several phosphorus dendrimers are effective as drugs by themselves (drug per se) and show their activity against neurodegenerative diseases, cancer, inflammation, ocular hypertension, and transmissible spongiform encephalopathies (TSEs) in both in vivo and in vitro. The present review discusses the synthetic route, fabrications, and biomedical applications of phosphorus-containing dendrimers. The toxicity of these dendrimers was also reported.