Drug Development and Industrial Pharmacy最新文献

Objective: To explore the application of artificial intelligence (AI) and machine learning (ML) in enhancing drug design and development processes within the pharmaceutical industry.

Significance: Drug design and improvement remain critical areas for chemical scientists and the pharmaceutical industry. Traditional drug development methods often suffer from low efficiency, unintended targeting, lengthy timelines, and high costs, posing significant challenges to the advancement of drug research.

Conclusion: Incorporating AI and ML technologies into pharmaceutical research can revolutionize the drug development landscape by making processes more efficient, precise, and environmentally sustainable. Continued advancements in AI-driven methodologies promise transformative impacts on healthcare and drug accessibility worldwide.

Background: The combined therapy of alpha arbutin, a natural derivative of hydroquinone, and niacinamide is well-regarded in skincare science. It leverages the unique properties of both actives, providing a multifaceted solution to esthetic and therapeutic skin concerns and supporting a comprehensive approach to skincare.

Objective: This study aimed to develop a robust HPTLC method to determine alpha arbutin and niacinamide in a nanocosmeceutical using a comprehensive approach that includes risk assessment and Analytical Quality by Design.

Methods: The critical method parameters influencing the HPTLC results were screened using a Plackett-Burman screening design, followed by optimization using a central composite optimization design and validation of the optimized method as per ICHQ2(R2).

Results: A novel HPTLC utilized pre-coated aluminum-backed HPTLC plates of Silica gel G 60 F₂₅₄ using 10 µL/band injection volume, and the plate was developed using an isocratic mobile phase consisting of ethyl acetate: methanol: water (8.4:0.8:0.8v/v/v) in a twin trough chamber pre-saturated for 30 mins with vapors of 10 mL of mobile phase. The separated components were detected at a wavelength of 273 nm. The developed HPTLC method resulted in a retardation factor of 0.31 ± 0.02 for alpha arbutin and 0.42 ± 0.02 for niacinamide, respectively. Validation results revealed the HPTLC method's specificity (peak purity ≥ 0.999), linearity (over a studied concentration range of 200-800 ng/band for alpha arbutin and 400-1600 ng/band for niacinamide), sensitivity, accuracy, precision, and robustness.

Conclusion: The developed robust HPTLC method was successfully implemented for the sustainable testing of the alpha arbutin and niacinamide in the nanocosmeceutical formulations.

Objective: This review aims to evaluate the synergistic potential of polymyxin B and silver nanoparticles (AgNPs) in combating multidrug-resistant (MDR) bacterial infections.

Significance: The alarming rise of MDR pathogens poses a critical global health challenge, necessitating novel therapeutic strategies beyond conventional antibiotics.

Methods: A comprehensive literature analysis was conducted to assess the mechanisms of bacterial resistance, the pharmacological profile and limitations of polymyxin B, and the antimicrobial activities of AgNPs. Special attention was given to nano-formulations combining both agents.

Results: Evidence suggests that the co-delivery of polymyxin B and AgNPs enhances antibacterial efficacy and reduces toxicity. Advanced delivery systems including polymeric nanoparticles, hydrogels, and transdermal platforms further improve drug stability, targeted delivery, and therapeutic performance.

Conclusions: The integration of nanotechnology with traditional antibiotics holds significant promise for overcoming MDR infections, and polymyxin B-AgNP nano-formulations represent a compelling direction for future antimicrobial therapy development.

Objective: Lenvatinib (LEN), a first-line treatment for advanced hepatocellular carcinoma (HCC), faces limitations due to adverse effects and drug resistance. This study aimed to develop LEN-loaded solid lipid nanoparticles (SLNs) modified with Twenty-polyglycerol vitamin E succinate (PG20-VES@LEN-SLNs) to enhance therapeutic efficacy and compare them with Tween80-modified SLNs (Tween80@LEN-SLNs).

Methods: The formulation of LEN-SLNs was optimized based on particle size and polydispersity index (PDI) by screening lipid matrices (GMS, GMP, SA, CP, GB, GMD), surfactant types (Tween80, PG20-VES, TPGS1000, F68), and GMS:SPC ratios. Physicochemical properties were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). Encapsulation efficiency (EE), drug loading (DL), and in vitro drug release profiles were evaluated. Cytotoxicity against HepG2, Huh-7, and L02 cells was assessed via MTT assay, while cellular uptake in HepG2 was visualized using Nile Red-labeled SLNs.

Results: Optimized PG20-VES@LEN-SLNs exhibited a smaller particle size (294.6 ± 10.4 nm vs. 308.6 ± 29.5 nm for Tween80@LEN-SLNs) and higher EE (80.7 ± 5.1% vs. 72.7 ± 4.0%). Both formulations showed sustained drug release over 48 h, significantly slower than free LEN (97.4% released in 24 h). PG20-VES@LEN-SLNs demonstrated superior cytotoxicity against HepG2 cells (IC50 = 36.47 μM) compared to Tween80@LEN-SLNs (IC50 = 42.49 μM) and free LEN (IC50 = 116.8 μM), with enhanced cellular uptake observed via confocal microscopy. In Huh-7 cells, PG20-VES@LEN-SLNs and Tween80@LEN-SLNs reduced the IC50 of lenvatinib from 189.21 μM (free LEN) to 18.04 μM and 18.41 μM, respectively.

Conclusion: PG20-VES@LEN-SLNs effectively improved LEN's therapeutic index through sustained release, enhanced tumor cell targeting, and synergistic cytotoxicity. This study highlights PG20-VES as a multifunctional surfactant for advanced HCC nanotherapy, offering a promising strategy to overcome clinical limitations of LEN.

Objective: To develop a pH-responsive drug delivery using chitosan-alginate hydrogel beads for enhanced therapeutic efficacy of omeprazole.

Significance: The developed system offers improved drug entrapment, release profiles, and enhanced bioavailability for omeprazole compared to commercial formulation.

Methods: pH-responsive chitosan-alginate hydrogel beads were prepared using a modified ionotropic gelation technique. The process was optimized via a two-level factorial design. Characterization involved drug entrapment efficiency determination, molecular dynamic simulations, in vitro drug release studies, and Caco-2 cell monolayer permeability assessments. Stability was evaluated under accelerated conditions, and in vivo efficacy was tested in rats with indomethacin-induced peptic ulcer disease.

Results: The optimized formulation achieved 82.70 ± 2.02% drug entrapment efficiency. In vitro release studies demonstrated superior pH-dependent behavior, with minimal release (<20%) at pH 1.2 and sustained release (>92%) at pH 7.4 over 24 h. Molecular modeling revealed high entrapment efficiency. The Caco-2 cell study showed a 2-fold increase in drug permeability (2.8 × 10^-6cm/s) compared with that of free omeprazole (4.5 × 10^-6cm/s) and a commercial formulation (3.7 × 10^-6cm/s), with no significant cytotoxicity (cell viability > 95%). In vivo studies demonstrated significant ulcer healing, reducing the ulcer index from 3.96 to 1.20. Accelerated stability studies indicated a 24-month shelf-life under normal conditions.

Conclusions: The novel chitosan-alginate hydrogel system offers a promising solution for improving omeprazole delivery, with significant enhancements in drug entrapment, release profile, bioavailability, and stability.

Objective: Seeds of Taxus chinensis contain effective anti-tumor substances. In this study, the main anti-tumor active compound was screened from Taxus chinensis seeds, which was combined with TPGS and mPEG-PCL to make micelles, improve its solubility and anti-tumor activity, and reduce the toxic side effects.

Methods: Organic solvent extraction, silica gel column chromatography, thin layer chromatography and other separation and purification techniques were used, combined with MTT method, to screen out the anti-tumor active fraction F5 (BE) from the ethanol extract of Taxus chinensis seeds, and then the main compound of BE, 20-hydroxyecdyone (20-HE), was obtained. High-pressure liquid chromatography (HPLC) was used to establish the in vitro analysis of BE and 20-HE. Afterward, BE micelle (BE-M) system was constructed via solvent injection combined with TPGS and mPEG-PCL and optimized using the single-factor screening experiment.

Results: BE-M were spherical micelles with particle size (34.37 ± 0.11) nm and polydispersity index (PDI) 0.152 ± 0. 003, possessing a high encapsulation rate (86.53 ± 1.54) % and drug loading (21.63 ± 0.87) %. The critical micelle concentration (CMC) value was very low at 0.881 μg/mL, indicating that BE-M has good stability. X-ray diffraction analysis (XRD) and Fourier transform infrared analysis (FT-IR) showed that BE had been successfully encapsulated in BE-M.

Conclusion: The results of MTT assay showed that the IC₅₀ values of BE-M against HepG2, A549 and U251 were lower than those of BE. This observation indicates that BE-M significantly improved the in vitro anti-tumor effect of BE.

Background: This study investigates Ginkgolic acid, a naturally occurring phenolic compound from Ginkgo biloba, for its potential to inhibit SARS-CoV-2 by targeting the RBD-ACE2 interface through a combination of computational and in vitro methodologies.

Methods: In silico molecular docking and 500 ns molecular dynamics (MD) simulations were employed to examine the binding conformation and stability of Ginkgolic acid at the RBD-ACE2 interface. In vitro studies included cytotoxicity profiling, plaque reduction assays, qRT-PCR, luciferase-based viral entry quantification, and membrane fusion inhibition in Vero E6 and ACE2-expressing HEK293T cells.

Results: Ginkgolic acid demonstrated dose-dependent antiviral activity in Vero E6 cells with half-maximal inhibitory concentration (IC₅₀) values ranging from 0.025 to 0.102 µM. MD simulations revealed its strong binding affinity at the RBD-ACE2 interface, particularly through interactions with conserved residues His34 and Asp38, leading to increased inter-residue distances and destabilization of the complex. In vitro assays confirmed significant virucidal activity, reduced viral entry, and inhibition of spike-mediated membrane fusion. Despite limited intracellular uptake, its antiviral efficacy appears to be predominantly extracellular.

Conclusion: Ginkgolic acid acts as an allosteric modulator and fusion inhibitor by targeting conserved RBD-ACE2 interface residues, disrupting viral attachment and fusion. Its dual mechanism-direct virucidal effect and host-cell entry inhibition-presents a promising scaffold for future antiviral development. These findings warrant further preclinical validation to assess its efficacy across SARS-CoV-2 variants.

Cathepsin C (CatC) is a lysosomal dipeptidyl peptidase that performs multiple physiological and pathological functions in the body. This review focuses on the complex biological roles of this enzyme in proteolytic networks, immune cell regulation, and cellular homeostasis. CatC is an enzymatic mediator that processes pro-inflammatory and cytotoxic precursors, such as neutrophil serine proteases, granzymes, and cathepsins. Recently, the role of CatC in inflammatory cascades, release, and immune modulation has extended far beyond its classical proteolytic function. Although CatC has been implicated in a wide range of pathologies, including autoimmune and neurodegenerative diseases, its therapeutic significance is unclear. The catalytic mechanism of sequential N-terminal dipeptide release offers the possibility of fine-tuning the proteolytic pathways. Genetic and biochemical evidence support its crucial role in cellular communication, inflammation, and immune regulation, making it an attractive candidate for therapeutic intervention. Emerging evidence suggests that CatC is a guardian molecule in pathogenesis and a novel therapeutic target. However, its multifunctionality necessitates specific interventions. This review synthesizes the findings, molecular mechanisms, and future perspectives, highlighting the potential of this enzyme to reshape therapeutic strategies for various diseases. For CatC inhibitors to reach their full therapeutic potential, barriers such as multifunctional regulation, systemic effects, and host-specific responses must be overcome in future studies. Omics technologies, biomarker discovery, combination treatments, and other novel approaches are expected to provide solutions for the management of inflammatory and immunological diseases, which would point toward addressing systemic diseases.

Objective: It was aimed to formulate blank and Arctium minus extract-loaded Polycaprolactone (PCL) and bilayer Polycaprolactone/Polyvinyl alcohol (PCL/PVA) electrospun herbal nanofiber scaffolds as bioactive wound dressings.

Methods: Electrospinning was used to produce nanofiber scaffolds and characterization studies of nanofibers (morphology, diameter) and the scaffolds (release, encapsulation efficiency, cytotoxicity, cell adhesion and proliferation, in-vitro wound healing, antioxidant activity) were carried out. MTT assay was used to determine the cytotoxicity of the fiber scaffolds on L929 mouse fibroblast cell line. Cell adhesion and proliferation were determined by imaging the cells seeded on scaffolds with scanning electron microscopy and fluorescent microscope. Wound healing assay was performed by creating an artificial wound (gap) to simulate the wound in the cell environment. The antioxidant efficacy of the extract produced from the scaffolds was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH●) and 2,2-Azino-bis3-ethylbenzothiazoline-6-sulfonic acid(ABTS●+) assays.

Results: All nanofibers were smooth and bead-free in the diameter range of 877.9-1257.9 nm, and had favorable encapsulation efficiency (91.9-97.5%), suitable in-vitro release. While the viability was between 71.4% and 73.6% in blank scaffolds, it increased up to 94.8-99.8% in extract-loaded scaffolds. However, all scaffolds can be used safely. All scaffolds (except blank PCL) provided a suitable environment for cell adhesion and proliferation. Both extract-loaded fiber scaffolds accelerated wound healing by improving cell migration. The amount of extract released was increased through formulation, demonstrating a strong capacity to scavenge DPPH● and ABTS●+ radicals.

Conclusion: In conclusion, A. minus extract-loaded PCL and PCL/PVA lead to significant enhancement in viability, adhesion, proliferation and in-vitro wound healing, indicating that they can be used as effective and safe wound dressings.

Objective: Different oils were used to develop nanoemulsion-based polyherbal mouthwashes (PHMs) of Cinnamon zeylanicum hydroalcoholic extract, and then their antibacterial activities against a range of oral pathogenic bacteria were assessed. Standard chlorhexidine acetate (CHD-A) was used as a control.

Methods: Different PHMs of C. zeylanicum extract based on nanoemulsions were obtained and the influence of various oils such as clove oil (CO), eucalyptus oil (EO), rose oil (RO), peanut oil (PO), and sesame oil (SO) on physicochemical and antibacterial characteristics of PHMs was studied. PHMs were characterized for the following parameters: droplet size, polydispersity index (PDI), refractive index (RI), transmittance (T), and pH. The optimized product was evaluated for size and shape on its surface using transmission electron microscopy (TEM).

Results: Nanoemulsion-based PHM prepared using CO showed the best physicochemical and antimicrobial properties compared to those prepared using EO, RO, PO, and SO. TEM investigation of an optimized formulation showed spherical-shaped droplets of formulation within the nanosize distribution of droplets. Against all oral infections, the antibacterial effects of the formulation made with CO (COPHM) were shown to be significantly greater than those of the formulation made with EO, RO, PO, and SO, as well as CHD-A. The formulation COPHM has been optimized as the final formulation based on minimum droplet size (31.41 nm), lowest PDI (0.141), ideal RI (1.336), highest %T (99.41), ideal pH (6.48), and largest antibacterial effects.

Conclusion: These results suggested the potential of nanoemulsion-based PHM in treating a range of diseases caused by oral pathogens.