Advanced pharmaceutical bulletin最新文献

Purpose: Hepatic stellate cells (HSCs) play a crucial role in fibrosis progression. we have developed a targeted delivery approach using A-functionalized nanoparticles for bortezomib (BTZ) specifically for activated HSCs in a mouse model of liver fibrosis.

Methods: The emulsion solvent evaporation method was used to form nanoparticles (NPs) targeted with vitamin A. The characterization of NPs was approved with Fourier-transform infrared (FT-IR), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Also, the biodistribution of NPs inside mice bodies was conducted via fluorescent drug. the cytotoxicity of NPs evaluated in different dose in vitro test. Compared to control groups, a serological evaluation, molecular examination and protein expression were performed based on BTZ's impact on fibrotic index on model mice after treatment with targeted NPs loaded with BTZ.

Results: Characterization of synthesized targeted NPs containing BTZ through DLS, X-ray diffraction (XRD) and FT-IR showed that the size of NPs was optimum and drug was entrapped inside of NPs successfully. Biodistribution of engineered targeted nanoparticles incorporating BTZ in mice showed a gradual tendency of NPs in the liver zone. Moreover, mice treated with vitamin A-targeted containing BTZ showed decreased expression of collagen I, collagen III, and α-SMA; also, the level of expression in TGF-β1/Smad3 and nuclear factor-kappa B (NF-κB) genes suppressed in mice treated with NPs entrapped BTZ. In line with these results, histopathologic and serological results showed significant exacerbation in non-target and drug-free nanoparticle-treated mice. The best result was seen in mice treated with targeted BTZ.

Conclusion: BTZ, in low amounts entrapped in targeted NPc, could ameliorate the fibrotic index in mice models.

Parkinson's disease (PD) stands as the second most prevalent neurodegenerative disorder, impacting a global population estimated between 6 to 10 million individuals. The condition primarily arises from a dopamine deficiency and the presence of α-synuclein, forming Lewy bodies in the substantia nigra pars compacta (SNcp). Despite the ongoing quest to unravel the precise pathophysiological mechanisms underlying PD, recent literature reviews posit that heightened activation of the Abelson non-receptor tyrosine kinase(c-Abl), in brain tissues plays a pivotal role in neurodegeneration observed in PD patients. Notably, these studies put forth compelling evidence suggesting that c-Abl inhibitors' interventions exhibit notable therapeutic potential. The potential benefits encompass enhancements in motor function, prevention of dopamine neuron loss, and the meticulous regulation of α-synuclein phosphorylation and clearance. These findings collectively advocate for the exploration of c-Abl as a prospective therapeutic target, thereby presenting inhibitors of this kinase as promising candidates for intervention in the management of PD.

Purpose: Cancer is a complex condition and gene therapy has evolved as a promising method for cancer treatment. Studies have demonstrated that PTEN and p53 proteins have remarkable antitumor effects but combined up-regulation of both PTEN and p53 genes has not been reported. We thus investigated their therapeutic potential in colorectal cancer (CRC) cells.

Methods: PTEN, p53, and blank vectors were purchased from Addgene, and transfected in SW480 cell line. Cell viability and apoptosis was assayed by MTT and flow cytometric analysis respectively. Real-time PCR assay was applied to assess changes in the expression of genes. To evaluate the effect on drug sensitivity of transfected cells, flow cytometric analysis was conducted.

Results: PTEN are more able to induce apoptosis than p53 in SW480 and PTEN and p53 demonstrated a synergistic anticancer impact. Further tests showed that both genes increased the change in the expression of genes related to cell cycle and apoptotic factors. Co-expression of these genes can also increase the susceptibility of CRC cells to the chemotherapeutic agent oxaliplatin.

Conclusion: According to our findings, cancer gene therapy targeting two tumor suppressors, like PTEN and p53 genes, might be a potent therapeutic approach for treating colorectal and other cancers.

Purpose: Blocking of inhibitory receptors such as NK group-2 member-A (NKG2A) enhances tumor immunity of natural killer (NK) cells. Additionally, antibody-dependent cellular cytotoxicity (ADCC) is an important cytotoxic modality of action of NK cells, which act as a functional bridge between innate and adaptive immunity. Here, we investigated the safety and feasibility of anti-NKG2A antibody-pretreated NK cells combined with IgG1 antibody (cetuximab) in patients with advanced gastric adenocarcinoma (GAC).

Methods: In this pilot study, treatment was initiated with cetuximab-based chemotherapy, followed by three times adoptive administration of anti-NKG2A pretreated NK cells (at doses 7×10⁸ cells/injection) at 5-day intervals in three unresectable and locally advanced GAC patients who enrolled regarding vital signs and clinical characteristics. The clinical signs, laboratory parameters, and CTCAE (Common Terminology Criteria for Adverse Events) were documented for a safety and feasibility assessment.

Results: The expanded cells were confirmed to be enriched in NK cells with high expression of CD56 (88.1%) and low expression of NKG2A (0.22%). The combination NK cell therapy was well tolerated, with transient adverse events. All patients were alive at the last follow-up (24 weeks). All patients showed overall decreases in tumor size and CA 19-9 level 4 weeks after combination therapy. However, two patients showed progressive disease (PD) after 12 weeks and the level of CA19-9 was increased in all three patients after 24 weeks.

Conclusion: In conclusion, this study demonstrated the safety and feasibility of infusing high doses of anti-NKG2A pretreated NK cells combined with cetuximab in patients with GAC.

Purpose: Rheumatoid arthritis is a persistent autoimmune condition characterized by joint inflammation and degradation, impacting individuals with varying degrees of severity. Chrysin is a natural flavonoid possessing diverse pharmacological properties and antioxidant and anti-inflammation activities. However, chrysin encounters limitations in bioavailability due to its low aqueous solubility and rapid metabolism. Targeted therapy using nanoparticle systems is a novel approach to overcome these difficulties.

Methods: The hyaluronic acid-decorated niosomal nanoparticles (NPs) were fabricated using the thin-film hydration method and characterized by various techniques (DLS, AFM, SEM, FT-IR, and drug release pattern analysis). The peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of patients with rheumatoid arthritis, and various factors levels, including nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-10, total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), as well as the expression levels of TIMP1, MMP9, and RANKL genes were evaluated.

Results: The fabricated NPs demonstrated spherical morphology with 199±10.7 nm size, 0.653 PDI, and -15.38±2.8 zeta potential. The FT-IR results confirmed the successful incorporation of substances inside niosomal NPs. The treatment with chrysin loaded niosomal NPs successfully decreased the inflammatory agent (nitric oxide), inflammatory cytokines (IL-1β and TNF-α), and osteoclastic related genes (MMP9 and RANKL) expression level. On the other hand, the activity of antioxidant agents (TAC, SOD, and GPx), anti-inflammatory cytokine (IL-10), and anti-osteoclastic related genes (TIMP1) were found to increase.

Conclusion: Taken together, the hyaluronic acid-decorated niosomal nano drug delivery system was acceptable in terms of characteristics and was able to direct the chrysin in the vicinity of PBMCs.

Monoclonal antibodies (mAbs) have gained increasing significance in biopharmaceutical research and production because of their precise targeting and therapeutic potential. The purification of mAbs is a crucial stage in production, ensuring the elimination of impurities for a top-quality, safe, and efficient final product. Chromatographic methods including affinity chromatography, ion exchange chromatography, and hydrophobic interaction chromatography (HIC) are commonly utilized to selectively capture and purify mAbs from complex mixtures by exploiting their unique properties, such as antigen-binding specificity or their surface charge and hydrophobicity. This review provides an overview of the current chromatographic techniques for mAbs purification, and to this aim delves into recent advancements and emerging trends in mAb purification, including the application of multi-modal ligands, membrane adsorbers, and continuous processing. These innovations aim to enhance efficiency, selectivity, and reliability while reducing processing time and costs, ultimately contributing to the development of safe and effective mAb-based therapies. Emphasis is placed on the necessity of choosing suitable methods based on the unique properties of the mAb and the desired quality attributes of the end product.

Purpose: Melasma is a persistent skin condition caused by excessive melanin production, particularly affecting women's quality of life. It can result from various factors like sun exposure, genetics, hormones, medications, or inflammation. Effective melasma treatment requires products that can deeply penetrate the skin. The outermost skin layer, known as the stratum corneum (SC), plays a crucial role in delivering topical and transdermal drugs. Researchers have developed numerous strategies to enhance skin permeability and drug efficacy.

Methods: This review delves into energy-based techniques and nanocarrier systems for treating melasma, specifically focusing on improving drug delivery to the viable epidermis (EP) while overcoming the SC barrier.

Results: Physical methods offer benefits such as enhanced skin penetration but come with drawbacks like frequent visits, high costs, and the need for specialized equipment and skilled operators. Microneedle patches are gaining attention as a convenient physical treatment option for delivering multiple medications effectively, offering targeted delivery and minimal side effects. Nanocarrier systems like transferosomes demonstrate promise in enhancing skin penetration for treating melasma and skin hyperpigmentation. While they offer advantages such as high drug entrapment and improved bioavailability, challenges like stability issues and scalability hinder their widespread adoption.

Conclusion: Energy-based techniques enhance drug penetration but can lead to scarring and burns, while dissolvable micro-needles offer a convenient and effective alternative. Nano-drug carriers, like nanostructured lipid carriers (NLCs) and transferosomes, show promise for improved skin drug delivery with their flexible structures and enhanced penetration capabilities, yet further clinical research is needed for definitive conclusions.

Purpose: Medicinal plants and their derivatives have been used to treat wounds, and loading the plants into nanoliposomes (NLPs) helps to increase their efficacy. This study investigated the efficacy of NLPs loaded with Withania somnifera (WHSE) extract in mouse models for excisional wound healing.

Methods: In the present study, we thoroughly evaluated WHSE's antibacterial, antioxidant, and safety profiles. Additionally, we assessed wound contraction, pathological evaluations, and the expression of basic fibroblast growth factor (bFGF) and CD31.

Results: The results showed that the extract and its NLPs had biocompatibility and exhibited antibacterial and antioxidant properties. Furthermore, our in vivo wound healing assay results showed that ointments containing 0.50% and 1.00% of the WHSE-NLPs accelerated wound healing and increased collagen and epithelialization. Furthermore, the results of the immunofluorescence and immunochemical tests indicated more expression of CD31 and bFGF in the mice that have been treated with WHSE-NLPs compared to those who were treated with WHSE and control groups. (P<0.05).

Conclusion: We demonstrated that the administration of 1.00% of the WHSE-NLPs could compete with the commercial ointment (Nitrofurazone®). Therefore, balms prepared from WHSE-NLPs expedited the wound healing process by increasing collagen, epithelialization, and the expression of CD31 and bFGF.

Purpose: Hijacked journals are fraudulent websites that mimic legitimate journals and, by charging authors, publish manuscripts. The current editorial endeavors to provide a close view of current literature. This editorial piece analyzes 10 years of research on hijacked journals and endeavors to shed light on future trends.

Methods: Current research uses a bibliometric approach to analyze data and discuss results. The OpenAlex has been used for data collection. Some of the data analysis was conducted using OpenAlex. The other study was done using Bibliometrix, and the date is limited to publication between 2014 and 2024.

Results: The findings provide a close view of the published literature in terms of access type, growth, topics, most frequent words, country contribution, top publishers, and alignment of literature with sustainable development goals.

Conclusion: The gap in current literature is the limitation in easily usable methods to be accessible by all researchers for hijacked journal detection and data analysis. The use of artificial intelligence can be promising.