Current pharmaceutical design最新文献

Introduction: Nanomedicine offers immense potential in the field of Central Nervous System (CNS) disorder treatment, encompassing conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and stroke.

Method: Through the utilization of nanotechnology-driven drug delivery systems, the efficacy of drugs can be amplified, their toxicity minimized, and their bioavailability increased, enabling them to effectively reach the intended site within the CNS. This review aims to examine the therapeutic possibilities that nanomedicine presents in addressing these debilitating disorders. This exploration entails an analysis of diverse nanotechnology- based approaches for CNS drug delivery, including polymeric nanoparticles, liposomes, dendrimers, and carbon nanotubes. Moreover, notable advancements in nanotechnology-based therapeutics for CNS disorders are highlighted, such as the application of nanoparticles for delivering curcumin in Alzheimer's disease, liposomes for delivering L-DOPA in Parkinson's disease, and dendrimers for delivering interferon-beta in multiple sclerosis.

Results: Additionally, the potential of nanotechnology-based approaches in the treatment of epilepsy and stroke is discussed. The review concludes by addressing the challenges faced and emphasizes the significant potential of clinical trials in enhancing drug delivery and future prospects in the development of nanotechnology- based therapeutics for CNS disorders.

Conclusion: Overall, the therapeutic potential of nanomedicine in CNS disorder treatment is vast, instilling optimism for the creation of safe and effective therapies for these devastating conditions.

Background: This study explores the formulation and effectiveness of a Rhodiola rosea phytosomal gel for enhancing wound healing.

Object: The ethanolic extract of Rhodiola rosea roots, rich in bioactive compounds like alkaloids and flavonoids, was optimized into a phytosomal complex to improve absorption and dermal retention.

Method: Characterization through GC-MS revealed compounds, such as 2-Heptadecenal and Bicyclo[ 4.1.0]Heptane and 7-Pentyl. FTIR confirmed the successful encapsulation within the phospholipid bilayer, while SEM showed smooth, spherical particles.

Result: The Box-Behnken design optimized formulation parameters, achieving high yield (92.64%), small particle size (355 nm), and high entrapment efficiency (93.98%). In vitro release studies displayed a consistent release profile, aligning with Zero-order and Hixson-Crowell models. In vivo evaluation on Wistar rats showed that the phytosomal gel significantly enhanced wound healing, achieving 98.16% wound reduction by day 14, compared to 95.17% for R. rosea extract and 97.13% for standard treatment. Histopathological analysis demonstrated complete tissue regeneration and well-organized collagen fibers in the phytosomal gel group.

Conclusion: This research highlights the potential of Rhodiola rosea phytosomal gel as an effective wound healing therapy, with future studies suggested for extended stability tests and human skin permeation studies.

Objective/background: This systematic review and meta-analysis aimed to evaluate the efficacy of narrow compared to wide surgical excision margins in the treatment of cutaneous malignant melanomas (MM) with Breslow thickness greater than 2 mm. All prior meta-analyses included studies analyzing patients with a variety of Breslow indexes. There is no prior meta-analysis analyzing the survival of the subgroup of MM patients with MMs > 2 mm in Breslow thickness. Hence, the aim of the present meta-analysis and systematic review was to examine the survival of the subgroup of MM patients with MMs > 2mm in Breslow thickness.

Methods: We followed the Cochrane Handbook for Systematic Reviews of Interventions and reported our findings in accordance with PRISMA guidelines. We included randomized controlled trials (RCTs) that compared narrow (1-2 cm) versus wide (3-4 cm) surgical excision margins for cutaneous melanomas thicker than 2 mm. Studies on non-cutaneous melanomas, observational studies, and non-randomized trials were excluded. Ten-year mortality rate and overall survival were the primary outcomes. Our searches were conducted in EMBASE and PUBMED databases.

Results: Three RCTs were included, with a total of 2,304 randomized patients. This meta-analysis showed no significant difference in 10-year all-cause mortality between narrow (2 cm) and wide (4 cm) margins (risk difference: 3.3%, 95% CI: -1.7% to 8.2%, p=0.202). Similarly, there was no significant difference in overall survival between narrow (1-2 cm) and wide (3-4 cm) margins (hazard ratio: 1.09, 95% CI: 0.974-1.214, p=0.3). Heterogeneity was low and non-significant.

Conclusions: This meta-analysis supports the non-inferiority of narrow (1-2 cm) surgical margins compared to wide (3-4 cm) margins for localized cutaneous melanomas with Breslow thickness greater than 2 mm. These findings suggest that narrow margins could be considered in surgical practice, although a 1 cm margin may be inadequate based on the results of individual studies. Further RCTs focusing on patients with localized MM thicker than 2 mm and taking into account modern adjuvant therapies and sentinel lymph node biopsies are recommended to refine surgical guidelines.

Gastrointestinal (GI) cancers, including gastric cancer, are among the most common and deadly cancers worldwide. Patients diagnosed with GI cancer still have a poor prognosis, largely resulting from the late stage of presentation for most of these patients and resistance to conventional therapy. This review covers new therapeutic strategies that apply advances in nanotechnology, immunotherapy, and drug delivery to overcome these challenges. Polymeric and metallic nanoparticles are distinguished for their potential to improve drug stability and solubility, as well as targeting drugs, thus diminishing systemic toxicity. The review centers around the use of immunotherapy in immune checkpoint inhibitors, CAR-T cell therapy, as well as the use of cancer vaccines to re-orient the immune system to be effective against cancer cells. Oncolytic viral therapy and bacteria- based treatments are unique non-conventional approaches that have a potential synergistic impact when used in concomitance with traditional methods. This review presents one of the most promising drug delivery systems: liposomes and micelles that can enhance pharmacokinetics and improve therapeutic results with controlled and site-specific release of anticancer agents. This review critically analyzes the strengths and challenges that include bioavailability, toxicity, and clinical translation, along with strategies to overcome such barriers. The review presents the most salient evidence to date and demonstrates the transformative potential of combining nanotechnology with immunotherapeutic and targeted treatments for managing gastric and other GI cancers. Future research should be focused on optimizing these platforms for clinical applications for the betterment of patient outcomes around the globe.

Breast cancer is a complex disease caused by the aberrant and unchecked proliferation of breast cells, which leads to the development of tumours. In various types of cancer, the Phosphoinositide 3- kinase/Protein kinase B (PKB, also known as Akt (PI3K/Akt) signalling pathway, is essential for controlling cell survival, metastasis, and metabolism. Currently, marketed PI3K inhibitors for treating breast cancer face several issues, including toxicity, resistance, etc. Significant efforts have been made to develop synthetic and repurposed inhibitor drugs to target PI3K, which are now being tested in clinical trials. Developed synthetic PI3K inhibitors have been reported to have better results in clinical trials in the suppression of tumors. This review article mainly focuses on the PI3K pathway at the cellular and molecular level, the development of PI3K inhibitors, and their clinical trials. Biomarkers, marine drugs, synthetic drugs, and repurposed drugs to treat breast cancer are also discussed, followed by mutational changes in PI3K and the resistance mechanism involved in PI3K inhibitors.

Psoralen, the simplest linear furanocoumarin, is derived from many medicinal plants, such as Psoralea corylifolia L., Glehnia littoralis Fr. Schmidt ex Miq., and Peucedanum decursivum (Miq.) Maxim. It has been used for treating osteoporosis and some skin disorders, including vitiligo, psoriasis, and atopic eczema. This review focuses on the pharmaceutical design of psoralen and the structure-activity relationships (SARs) of its derivatives. It also includes the biosynthetic pathways, metabolic characteristics, metabolites, and clinical uses of psoralen, as well as its toxicity/side effects and relevant mechanisms. Psoralen, as a promising drug lead compound, is structurally modified to develop numerous derivatives with remarkable biological activities. SARs discussed herein can guide the design and development of novel psoralen-based derivatives for use in pharmaceuticals and widen their therapeutic potencies.

Aims: To enhance curcumin's bioavailability with the help of carbon dot and piperine, due to its promising anticancer activity.

Background: Cancer is a disease condition, where some cells grow uncontrollably, and if not controlled, they spread to other parts of the body. Concerning anticancer agents, curcumin has anticancer properties along with anti-inflammatory, antimicrobial, and antioxidant. Here in this study, the pharmacokinetic property was improved with the help of Carbon Dot encapsulation.

Objective: To improve the bioavailability of curcumin by improved encapsulation efficiency in carbon dots, to achieve a better cytotoxic effect of curcumin.

Methods: Bamboo leaves were used for the preparation of CDs and curcumin was loaded in them and the characterization for particle size, morphology, loading capacity, quantum yield, drug release in vitro studies, and in vitro cell viability activity as anticancer activity was done accordingly.

Results: Prepared CDs have a smaller particle size (< 10 nm), good loading capacity, stability, and excellent fluorescence activity. Studies on the release of curcumin have shown that a pH-5.5 solution leads to enhanced curcumin release. The CDs-curcumin shows enhanced toxicity against cancerous cells than the curcumin even at lower concentrations (20, 40, 60, 80,100 μM).

Conclusion: Curcumin can be delivered by CDs, which have the advantages of increased bioavailability, small size, high loading capacity, improved photoluminescence, and biocompatibility. These characteristics can result in improved anticancer activities even at low concentrations.

SARS-CoV-2, the virus responsible for COVID-19, has resulted in a devastating global impact with millions of lives lost. Remdesivir and 2-DG are among the few drugs authorized for emergency use against COVID-19, but concerns about their efficacy and side effects persist. Vaccines have been developed and approved, yet the emergence of viral mutations has raised questions about their effectiveness against new variants. Natural compounds with antiviral properties have shown promise in combating SARS-CoV-2. The review highlights the potential of medicinal plant compounds, particularly in targeting the virus' main protease, a crucial component for viral replication. Natural, plant-derived compounds represent a promising avenue for COVID-19 therapeutics. Further clinical validation is necessary to ascertain their efficacy and safety in treating COVID-19. This underscores the importance of continued research into alternative treatments for combating this global health crisis. This review examines the potential of natural, plant-derived compounds as safe and cost-effective alternatives for combating COVID-19. It summarizes the pathogenesis of SARS-CoV- 2 and the ongoing drug studies and identifies natural compounds with known antiviral properties. Additionally, it explores the potential of medicinal plant compounds in targeting the SARS-CoV-2 main protease through in silico and molecular docking studies.

Introduction: In this study, pure and cobalt manganese-doped ZnO nanoparticles (Zn(1-x-y)MnxCoyO NPs) at varying concentrations were synthesized through sol-gel method, and zinc acetate dihydrate, manganese nitrate, cobalt acetate, and diethyl amine were used as precursors, with samples finally calcined at 700oC.

Method: The hexagonal wurtzite structure of pure and co-doped ZnO NPs was confirmed by X-ray diffraction (XRD). The computed grain sizes of pure and co-doped ZnO NPs, according to Scherrer's formula, were 32 nm, 32.5 nm, 36.3 nm, and 36.5 nm, respectively. SEM was used to observe the morphology of nanoparticles. FTIR spectroscopy was used to examine the chemical make-up and vibrational modes of pure and co-doped ZnO NPs. The bandgaps of pure and doped ZnO were examined using UV-Vis spectroscopy.

Results: It was found that the optical bandgap of ZnO was lowered by 3.21 eV by manganese and cobalt doping. Elemental composition analysis was performed by using EDX analysis. Finally, anticancer activity of pure and co-doped ZnO NPs was assessed by employing MTT assay, which indicated that Zn0.8 Mn0.1 Co0.1O NPs showed significant anticancer results against liver cancer (HepG-2) cells as compared to ZnO, Zn0.98 Mn0.01Co0.01O and Zn0.90 Mn0.05 Co0.05O NPs. Moreover, Zn0.8 Mn0.1 Co0.1O NPs showed low toxicity and good biocompatibility comparable to doxorubicin (DOX).

Conclusion: Comprehensive experimental findings have demonstrated an authentic way of obtaining feasible in vivo liver cancer therapy.