Journal of Pharmaceutical Innovation最新文献

Purpose

Breast cancer remains a leading cause of cancer-related death among women worldwide. The advancement of targeted therapies to enhance efficacy and reduce systemic toxicity is essential. The aim of this study was to develop hyaluronic-acid coated nanoparticles for the targeted delivery of palbociclib, utilizing poly(lactic-co-glycolic acid), by applying QbD approach.

Methods

The nanoparticles were developed using single-emulsion solvent evaporation technique. Utilizing the QbD approach, a QTPP was defined, and a comprehensive risk assessment was conducted. A 2⁷⁻³ fractional-factorial design was used to identify the factors affecting the particle size and entrapment efficiency. A Central-composite design was employed to obtain the optimized formulation, yielding a particle size of < 200 nm and high encapsulation efficiency. The optimized NPs were then surface modified with hyaluronic-acid and tested on MCF-7 cell lines.

Results

The particle size, zeta potential and entrapment efficiency of optimized and coated nanoparticles were 188.38 ± 1.35 nm, -27.23 ± 1.67mV and 85 ± 2.14%; 195.7 ± 1.45, -28.52 ± 2.32mV and 84.78 + 2.67% respectively. The nanoparticles were spherical in shape with smooth surface. The nanoparticles were < 200 nm and preferentially accumulated in tumour sites attributable to the enhanced permeation and retention.

Conclusion

The hyaluronic-acid coated nanoparticles exhibited enhanced cytotoxicity, apoptosis, and nuclear damage compared to the optimized formulation and the free drug. This is likely attributed to the increased affinity of hyaluronic-acid to CD44 receptors, which are overexpressed in cancer cells, thus facilitating a targeted approach.

Graphical Abstract

The main objective of the research was to develop and optimize a transdermal drug delivery system (TDDS) for Nadolol, a non-selective β-blocker with limited oral bioavailability (~ 30%) due to hepatic first-pass metabolism. Nadolol has possess a favourable properties for transdermal delivery, such as a moderate lipophilicity (log P ~ 1.2), a relatively low molecular weight (309.4 g/mol), and a long elimination half-life, which render it a suitable candidate for sustained systemic delivery through the skin. Transdermal patches were formulated using the solvent casting method with varying concentrations of hydroxypropyl methylcellulose (HPMC K4M) and propylene glycol (PG). A 3²-factorial design was employed to optimize the chosen independent variables (X1: HPMC K4M concentration: X2: propylene glycol concentration) concerning the dependant variables (Y1: % cumulative drug release, Y2: tensile strength and Y3: % elongation). The prepared patches were evaluated for mechanical properties, moisture content, drug content uniformity, in vitro release, ex vivo permeation, and physicochemical compatibility using FTIR and DSC studies. The results confirmed that the drug was compatible with the selected excipients, and all patches demonstrated good flexibility, tensile strength, and sustained drug release over 12 h. Among all formulations, batch N7 (HPMC K4M 5%, propylene glycol 0.1 mL) showed the best performance, with a cumulative drug release of 97.79%, a flux value of 4.8990 mg/cm²/h, and desirable mechanical strength. Ex vivo studies using shed snake skin supported the in vitro release findings, with drug permeation reaching 89.81%. The release kinetics followed zero-order and Fickian diffusion. This study reveals Nadolol as a promising candidate for transdermal delivery and illustrates that factorial design-based optimization of an HPMC patch can yield a simple, scalable, and economical approach for sustained release and enhanced bioavailability. Although in vivo and long-term stability investigations remain necessary, the results provide a robust basis for subsequent preclinical research.

Paracetamol (PCM) overdosing-induced hepatotoxicity is a chief cause of acute liver toxicity. Andrographolide (APD) upregulates the Nrf2 level in hepatocytes, inhibits activation of NF-kB pathway and lipid peroxidation, as well as mitigates the release of pro-inflammatory mediators. However, APD meets several challenges, such as limited oral bioavailability (15.87 ± 3.84%), poor solubility (3.29 ± 0.73 µg.mL^− 1), and gastric milieu susceptibility. Therefore, in the present investigation, parenteral poly(ε-caprolactone) microparticles of andrographolide (APD-PCL-MPs) were engineered using an oil-in-water (O/W) emulsion solvent evaporation method under optimized processing conditions assessed by Box-Behnken Design (BBD; 3-factors, 3-levels). The APD-PCL-MPs exhibited a particle size of 1.47 ± 0.19 μm, ζ-potential of -29.44 ± 0.92 mV, 4.57 ± 0.03% drug loading (% DL), and 70.40 ± 1.35% entrapment efficiency (% EE). Comprehensive characterizations by FTIR, TGA, DSC, and P-XRD analyses authenticated efficient entrapment, enriched thermal stability, and molecular amorphous dispersion of the therapeutic entity post-microencapsulation. The in-vitro drug release profile verified sustained drug release up to 96 h by following Higuchi and Korsmeyer-Peppas kinetics. Further, andrographolide loaded poly(ε-caprolactone) microparticles once a day through intravenous route at the dose of 10 mg/kg for 7 days attenuated PCM (3 g/kg)-induced hepatotoxicity owing to targeted and sustained release of therapeutic entity, as evidenced by normalization of biochemical markers, hepatic antioxidant enzyme levels, lipid peroxidation, and proinflammatory mediators (IL-6 and TNF-α). Andrographolide-loaded poly(ε-caprolactone) microparticles once a day through the intravenous route preserved hepatic cytoarchitecture with markedly reduced necrosis, vascular congestion, diffused sinusoidal dilation, and inflammatory infiltration. In conclusion, andrographolide-loaded poly(ε-caprolactone) microparticles once a day through the intravenous route may be a promising therapeutic modality for translating into a clinically viable product.

Graphical Abstract

Background

Rheumatoid arthritis (RA) is an autoimmune chronic illness affecting 0.5% to 1% of the population. Traditional medicinal plants, which are pivotal in drug discovery, prompted the investigation of Pueraria tuberosa (PT) tuber for its anti-rheumatic properties.

Purpose

Aqueous extract of PT and Pueraria tuberosa loaded silver nanoparticle (PTAgNP) were investigated for their effects in Freund’s Complete Adjuvant induced RA in rats.

Methods

In vivo evaluation using the Freund’s complete adjuvant (FCA) induced arthritis model and Pueraria tuberosa tuber extract at a dose (200, 400 mg/kg) and PTAgNP 100 mg/kg was used as a treatment for about 21 days. NPs were characterized using UV, XRD, SEM, and zetasizer. After 21 days of treatment, oxidative stress in paw tissue, biochemical parameters, inflammatory cytokines, x-ray, and histopathological analysis of the ankle joint were evaluated.

Results

PT and PTAgNP showed treatment significantly ameliorates the adjuvant induced arthritic scoring, histological alterations, paw volume, elevation of biochemical (AST, ALT, ALP, CRP) and restored the endogenous anti-oxidant (SOD, GSH, MDA) activities. Significant reduction in paw swelling, arthritis score and weight of spleen in treatment groups. An Increased in body weight, indicating improvement of the disease condition. Biochemical analyses indicated reduced ESR, WBC and increased levels of RBC and Hb, suggesting decreased inflammation. There was also a significant decrease in levels of TNF-alpha and IL-6 pro-inflammatory cytokines in treatment groups. Radiological examination showed reduced soft tissue swelling and joint changes in the treated groups.

Conclusion

PT and PTAgNPs showed anti-arthritic effects through anti-oxidant activity, reduction of inflammatory markers and improvement in joint parameters. These findings support further exploration of PT and the nanoparticles demonstrated significant antiarthritic activity against rheumatoid arthritis induced by complete Freund’s adjuvant in experimental rats, surpassing the effects of the extract and standard indomethacin. Pueraria tuberosa loaded silver nanoparticles showed as potential source as a novel anti-arthritic drug.

Objective

The objective was to create AQbD approach novel green stability-indicating RP-HPLC method that can measure Evogliptin tartrate (EVO) and Metformin HCl (MET) in their combined dosage form dosage form at the same time and greenness assessment of method by using AGREE and GAPI matrices.

Materials and Methods

Initial screening experiments, combined with a structured risk assessment, were conducted to identify the critical method attributes (CMAs), specifically the proportion of organic modifier, buffer pH, and flow rate, all of which impact the critical quality attributes (CQAs). A Box-Behnken design was employed within the response surface methodology framework to evaluate the three-level interactions of these parameters. The effects on 5 key response factors—Retention Time of EVO (R1), Retention Time of MET (R2), Tailing Factor of EVO (R3), Tailing factor of MET (R4) and Resolution (R5) were analyzed in detail. The suggested approach was created utilizing an Eclipse C18 column, a mobile phase consisting of 5-mM 1-hexane sulphonic acid sodium salt in water, and 0.2% v/v TEA: Methanol with pH 3.0 adjusted with orthophosphoric acid (OPA). The study investigated at the forced degradation of pharmaceuticals under different stress settings. Using a PDA detector, the degradant products and both drugs demonstrated high peak resolution at 254.4 nm. AGREE and GAPI software’s were used for greenness assessment of method.

Results

With r2 values > 0.999, which demonstrate a strong linear relationship between concentration and peak area, this approach demonstrated good linearity for the concentration range used: 1–5 µg/mL for Evogliptin tartrate and 100–500 µg/mL for Metformin HCl. Since the recovery percentage falls between 99 and 100%, it was shown to be accurate without interfering. Measurements of intra-day and inter-day precision showed that the medicines' RSD was less than 2%. For Evogliptin tartrate, the LOD and LOQ were 0.047 µg/mL and 0.143 µg/mL, while for Metformin HCl, they were 5.81 µg/mL and 17.61 µg/mL. The technique's capacity to identify stability for both medications was confirmed when it was able to distinguish the degradation products. The developed RP-HPLC method has an AGREE score of 0.63 and In GAPI pictogram showing only three red zones which corresponding to Physico-chemical properties, non- greener solvent used and no waste treatment.

Conclusion

The proposed method effectively optimized by using BBD. After being evaluated by ICH requirements, the proposed method was determined to be robust, straightforward, specific, precise, and accurate. It will be appropriate for regular quality control and stability studies, guaranteeing the product's ongoing safety and effectiveness. The developed method was evaluated using AGREE and GAPI tools and both of which showed excellent green characteristics.

Summary

Rana-2PN, identified as the first member of the Ranatuerin antimicrobial peptide family, has been reported to exhibit lipopolysaccharide neutralization, anti-inflammatory effects, and broad-spectrum antimicrobial properties. Besides these biological activities, the potential interactions and effects of this compound on cancer cell lines remain unexplored. In this study, our results indicate that Rana-2PN inhibits the proliferation of K562 cells (IC₅₀ = 4.52 μΜ) and induces significant morphological changes. Flow cytometric analysis using FITC-labeled Rana-2PN revealed its concentration-dependent binding to K562 cells. Furthermore, Rana-2PN treatment upregulated the mRNA expression of key necroptosis markers RIPK1, RIPK3, and MLKL, as quantified by RT-PCR, and promoted necroptotic cell death, which was confirmed by Annexin V-FITC/PI staining and partially inhibited by necrostatin-1. Mechanistically, Rana-2PN induced mitochondrial dysfunction, evidenced by loss of mitochondrial membrane potential (detected by JC-1 staining) and increased mitochondrial permeability (measured by Calcein-AM assay), accompanied by concentration-dependent ROS accumulation (using DCFH-DA staining). In summary, our study provides the possibility of future development of Rana-2PN as a novel therapeutic candidate for the treatment of chronic myelogenous leukemia, particularly in cases where resistance to conventional therapies may develop.

Background

Acne vulgaris, a chronic inflammatory condition of sebaceous glands, is often linked to microbial colonization (e.g., Cutibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus) and inflammatory factors. This study explores the potential of Eucalyptus galbie and green tea (Camellia sinensis) extracts, delivered via niosomes, to combat acne. Niosomes, non-ionic surfactant vesicles, offer targeted drug delivery and improved pharmaceutical properties, particularly for topical applications.

Methods

Eucalyptus and green tea extracts were obtained via hot maceration, standardized for phenolic and flavonoid content, respectively. Niosomes, encapsulating 2% (w/v) of Eucalyptus and green tea extract (EGTN) were provided using the thin-film hydration method. Three selected EGTNs were characterized for particle size, physical stability, extract retention, and release study. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were performed against S. aureus and S. epidermidis to evaluate antimicrobial activity.

Results

Optimal EGTNs with varying ratios of cholesterol, tween 40, span 40, tween 60, and span 60 were prepared. The combination of ST40/cholesterol (70:30) (EGTN of E1) exhibited the most promising antimicrobial activity, favorable particle size, stability, retention, and sustained release of the plant extracts. The MIC and MBC values against S. aureus and S. epidermidis were approximately 1250 µg/mL and 312.5 µg/mL, respectively.

Conclusion

In conclusion, niosomal structures enhance antibacterial effect, stability, and release profile of plant extracts compared to the non-niosomal form. The E1 niosome showed promise as an anti-acne product, warranting further toxicological and clinical evaluation.

In this paper, a novel framework called DeepFusionNet is presented. It is intended to accurately classify lung diseases using multi-modal imaging data, including CT, MRI, and X-ray images. Modern deep learning methods, such as TrifectaNet for reliable illness categorization and LungSegNet + + for precise lung segmentation, are integrated into the system. The suggested approach includes pre-processing, deep learning-based detection, feature extraction, feature selection, and identification of regions of interest. To be more precise, it uses median filtering to reduce noise, bilinear interpolation to resample, and Gamma Correlated Contrast Limited Adaptive Histogram Equalization (G-CLAHE) to normalize intensity across all modalities. In addition, the system makes use of modality-specific characteristics for thorough feature extraction, including statistical moments, Local Binary Patterns, edge detection, density histograms, and shape descriptors. The Hybrid Pufferfish-based Coati Optimization (HPCO) method is used for feature selection in order to find the most informative characteristics. Ultimately, SqueezeNet, Bidirectional Recurrent Neural Network (Bi-RNN), and Triplet Siamese Network models work together in a TrifectaNet ensemble model to perform classification, and Grad-CAM-based visualization is used to analyze and explain the classification choices. Compared to the current methods, the suggested model outperformed them, achieving 99.28% accuracy for 80% of the training set.

Purpose

The aim of the current study was to develop and evaluate the therapeutic potential of apocynin loaded pH-sensitive nanoparticles (APO-NPs) based transdermal hydrogel for management of rheumatoid arthritis (RA). 

Methods

Slightly modified nanoprecipitation technique was used for preparation of polymeric nanoparticles. Optimization was done through design expert software. Optimized APO-NPs were loaded into carbopol-934 based hydrogel as final dosage form.

Results

Optimized APO-NPs formulation showed a minimum particle size 63.44 nm, polydisperibility index 0.161, and zeta potential − 15mV, along with a maximum encapsulation efficiency 89%. In-vitro and ex vivo studies of APO-NPs based hydrogel were performed at pH 5.5 (pH of normal skin) and 6.8 (pH of inflamed joint) showed a pH-responsive sustained drug release and increased penetration in comparison to free APO based hydrogel. The stability studies of APO-NPs based hydrogel were performed to strengthen the potential use of the prepared formulation through transdermal route. Assessment and therapeutic efficacy of prepared pH-sensitive nanocarriers system was evaluated in chronic RA mice model. Parameters associated with chronic inflammation were investigated including behavioral changes, histopathological, and radiological x-rays images of joints of mice hand paws. In vivo study depicts improvement in the behavioral parameter, decline in synovial hyperplasia and bone structure restoration.

Conclusion

thus, the APO-NPs based transdermal hydrogel is a promising carrier system that can effectively manage RA.

Graphical Abstract