Assay and drug development technologies最新文献

The primary objective was to find the pharmacological targets of doxorubicin and their mechanisms of action, with a dual focus on their therapeutic relevance in skin cancer treatment and their potential involvement in resistance to doxorubicin in cancer cells. The targets of skin cancer and potential targets of doxorubicin were searched from multiple databases. Common targets were chosen using the GeneVenn tool and then imported into the STRING database to construct a protein-protein interaction network. Topological factors were evaluated with Cytoscape to identify core targets. FunRich was used to identify the signaling pathways, molecular functions, cellular components, and biological processes involving the top targets. Molecular docking was conducted using the Molecular Operating Environment software. The top five target genes identified as therapeutic targets of doxorubicin for treatment of skin cancer are poly(ADP-ribose) polymerase, epidermal growth factor receptors, heat shock protein 90 alpha family class A member 1, Harvey rat sarcoma viral oncogene homolog, and mammalian target of rapamycin. In addition, doxorubicin-induced resistance mechanisms were also predicted. Further research on innovative methods of delivering doxorubicin to maximize its effectiveness in treating skin cancer and to prevent the development of resistance to the drug is necessary.

Diabetes management necessitates innovative approaches to enhance treatment efficacy and patient adherence. The study aimed to develop a transdermal patch loaded with emodin, hypothesized to provide a noninvasive treatment option that circumvents complications of oral administration. To optimize the formulation, a full factorial experimental design was employed, focusing on the concentrations of hydroxypropyl methylcellulose K15 and geraniol. Compatibility and mechanical characteristics were investigated using Fourier-transform infrared spectroscopy and differential scanning calorimetry. The patch's drug release profile was assessed via in vitro studies, while its stability was tested under accelerated conditions. The antidiabetic efficacy was evaluated in diabetic rats using an in vivo model. The optimized patch (batch SF7) released 94.57% of the drug over 12 h. Under accelerated stability conditions, the patch showed a minor decline in folding endurance from 396 ± 1.50 to 369 ± 2.63 folds and drug content uniformity from 98.70% ± 0.02% to 98.14% ± 0.23%. The in vivo antidiabetic study demonstrated a considerable decrease in blood glucose levels in SF7-treated rats from 245.83 ± 3.25 mg/dL to 120.86 ± 4.24 mg/dL over 12 h (p-value < 0.001), comparable with the standard drug glibenclamide. The emodin-loaded transdermal patch displayed consistent drug release, maintained stability, and demonstrated significant antidiabetic activity, suggesting that it is a promising noninvasive therapy for diabetes management.

Drug delivery systems are now being advanced by integrating sophisticated nanotechnologies to enhance therapeutic efficacy. Tremendous advancement has been achieved in the field of cancer therapy through the utilization of hyaluronic acid-based nanocarriers, which are well-acknowledged for their capacity to transport medication precisely to targeted regions. Quantum dots exhibit unique optical properties that allow for precise drug administration and monitoring capabilities. Carbon nanotubes provide a large surface area and exceptional strength, allowing for precise manipulation of drug delivery patterns. Dendrimers are versatile structures that can transport many drugs simultaneously, whereas mesoporous silica-functionalized nanoparticles allow exact manipulation of the release rate of pharmaceuticals. Polymer-lipid hybrid nanoparticles synergistically integrate the durability of polymers with the compatibility of lipids, hence augmenting the availability of drugs within the body. Hexagonal boron nitride nanosheets are becoming more recognized as favorable carriers due to their biocompatibility and potential for tailored administration. These achievements demonstrate the changes happening in the field of pharmaceutical administration, where nanotechnology is used to tackle issues such as restricted bioavailability and unanticipated adverse effects. This ultimately enhances the effectiveness of medicines and improves patient outcomes. Future investigations will focus on improving these technologies for broader therapeutic applications.

Viral diseases remain a significant challenge for global health with rising fatalities each year. In vitro assays are crucial techniques that have been utilized by researchers in the quest to develop antiviral therapies. These assays mimic the internal conditions of a living system and make it possible to study how antiviral compounds interact with such systems in a laboratory setting. Thus, the importance of in vitro assays cannot be overemphasized, as they provide an accurate means for assessing the efficacy of potential antiviral compounds. This review offers an overview of in vitro antiviral assays, the different types of cell lines used, and emerging techniques and applications that have been developed in recent times. The current review also assesses challenges that are encountered in antiviral drug research, as well as emerging technologies like microfluidics and three-dimensional cell cultures. The integration of computational models and multiparametric assays into antiviral research was noted to significantly improve antiviral drug development process.

Freeze-drying is popular for producing pharmaceutical formulations with structurally complicated active components and drug delivery system carriers. It is the process of eliminating water from ice crystals through the sublimation mechanism. Some formulations may require drug-specific excipients such as stabilizers, buffers, and bulking agents to maintain the appearance and assure the long-term stability of the drug product. This approach is utilized for therapeutic compounds that are moisture sensitive, thermolabile, and degrade in the atmosphere. Freezing and primary and secondary drying are critical processes in the lyophilization process because they directly impact the end result. This approach is effective for producing a variety of dosage forms, including oral, inhalation, and parenteral. As a result, lyophilization may be an important method for improving the therapeutic efficacy and delivery of various dosage forms delivered via different routes. Additionally, lyophilization is used in pharmacological research to preserve biological samples, stabilize reference/standards, and increase the solubility and bioavailability of poorly soluble drugs. Thus, lyophilization is critical for maintaining the stability, efficacy, and safety of pharmaceutical products throughout their development and lifecycles. This article includes a broad overview of the lyophilization process, principle, excipients for lyophilized medicine compositions, and new lyophilization technologies as well as their applications in a variety of fields.

To optimize the formulation of docetaxel-zedoary oil magnetic solid lipid nanoparticles (DTX-ZTO-MSLN) using central composite design-response surface methodology. First, the formulation and preparation process of DTX-ZTO-MSLN were optimized via design-response surface methodology. The appearance, particle size, thermogravimetric, pH, iron content, magnetic strength, and in vitro drug release of DTX-ZTO-MSLN were subsequently examined. Finally, the antitumor effect of DTX-ZTO-MSLN on MCF-7 breast cancer cells was measured via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The optimized formulation was as follows: the mass ratio of soybean phospholipid to poloxamer 188 was 0.34, the mass ratio of DTX-ZTO to glycerol monostearate was 3.23, and 29.42 mL of water was used. The DTX-ZTO-MSLN prepared by the optimized method was clear and transparent, with good stability, with an iron content of 7.38%, and a saturation magnetization intensity of 7.05 A·m²·kg^-1. The in vitro drug release was consistent with the Weibull model (R² = 0.9992). Compared with zedoary turmeric oil and docetaxel, DTX-ZTO-MSLN had a much greater inhibitory effect on MCF-7 cells (p < 0.05). The optimized DTX-ZTO-MSLN meets the quality requirements for nanoemulsions. This study provides a theoretical basis for developing and applying DTX-ZTO-MSLN.

Skin is one of the largest organs in the human body. It acts as an outer protective cover and comprises the epidermis, dermis, and hypodermis. Liposomes are formed by phospholipids and have a vesicular character that improves the encapsulation of lipophilic, hydrophilic, and amphiphilic drugs. The invasome structure is flexible as opposed to regular liposomes; this is due to the presence of ethanol and terpene that increases lipid fluidity in the vesicle structure. Terpenes, ethanol, or terpene mixes are potential carriers that invasomes' tiny liposomal vesicles used to improve skin penetration. Terpenes that are primarily derived from natural sources are the most efficient and secure kind of penetration enhancers (PEs). There are some methods for the preparation of invasomes, but mostly the techniques used for the preparation of invasomes are mechanical dispersion and film hydration methods. Although PEs are effective when applied topically, only a small number are clinically approved due to concerns about skin irritation and toxicity. Invasomes exhibit a higher rate of skin penetration than liposomes and ethosomes. This review examines the structure, components, preparation methods, and applications of invasomes in pharmaceutical formulations, focusing on their potential to treat skin disorders and improve therapeutic outcomes. The primary objective is to assess the future potential of invasome technologies in transdermal drug delivery, alongside an exploration of the regulatory challenges and pathways for their development and approval. Graphical abstract illustrating the composition, mechanism of action, and therapeutic applications of invasomes in transdermal drug delivery systems.

This study aimed to elucidate the hepatoprotective mechanisms of microalgal fatty acids (MFA) from Schizochytrium against alcoholic liver disease (ALD) through network pharmacology and in vivo analysis. Network pharmacology and molecular docking methodologies were employed to predict the potential mechanisms of MFA against ALD. To substantiate these predictions, an acute alcoholic liver injury mouse model was utilized to assess the impact of MFA on serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total protein (TP), and albumin (ALB). Additionally, liver histopathology and the expression levels of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) protein were evaluated. Seven active ingredients and 53 potential targets (including 7 core targets) for ALD treatment were identified in MFA. Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these seven core targets are implicated in various biological pathways, notably those associated with cancer, viral infections, and the PI3K/AKT signaling pathway. Furthermore, molecular docking studies demonstrated that docosahexaenoic acid and docosapentaenoic acid in MFA exhibited strong binding affinity for these seven crucial targets. Animal experiments demonstrated that administration of MFA significantly decreased the levels of AST, ALT, and ALP, while increasing the levels of ALB and TP in mice with acute alcoholic liver injury. Moreover, MFA ameliorated liver tissue pathology and markedly down-regulated the expression of PI3K and AKT proteins in the liver. These results suggest that MFA may possess therapeutic potential for ALD by targeting multiple pathways, with its mechanisms likely involving the inhibition of the PI3K/AKT signaling pathway.

Glycerosomes signify a groundbreaking advancement in drug delivery technology. Comprising glycerol, phospholipids, and water, glycerosomes offer superior drug stability, penetration, entrapment efficiency, fluidity, and viscosity compared with conventional liposomes. Their formation process eliminates the need for specific transition temperatures, streamlining production. Glycerol's plasticizing properties enhance vesicle elasticity and flexibility, enabling enhanced skin penetration. These vesicles demonstrate immense promise across a range of drug delivery pathways. In dermal and transdermal applications, glycerosomes augment drug permeation by moisturizing the stratum corneum and improving membrane fluidity. For oral delivery, they shield drugs from the harsh gastrointestinal environment and boost intestinal absorption. Pulmonary delivery benefits from glycerosomes' capacity to stabilize and disperse aerosolized vesicles, facilitating deep penetration into lung tissues. Ophthalmic applications profit from increased corneal penetration and extended retention. Intranasal use of glycerosomes enhances mucosal penetration and enables direct drug delivery to the central nervous system by circumventing the blood-brain barrier. Ongoing advancements in glycerosome technology concentrate on integrating diverse functional ingredients like essential oils, β-sitosterol, sodium hyaluronate, and trimethyl chitosan to develop specialized formulations. These variants include STO-glycerosomes, S-glycerosomes, PO-S-glycerosomes, HY-glycerosomes, TMC-glycerosomes, glycethosomes, and glycerospanlastics, all offering enhanced stability, permeability, and therapeutic efficacy. This review delves into the mechanisms of drug transport within glycerosomes, their applications in various delivery routes, and the latest technological developments, highlighting their substantial potential as versatile carriers in contemporary drug delivery systems.