National Institute of Pharmaceutical Education and Research, Guwahati (NIPER-Guwahati) established 2008, is an Indian public Pharmacy research university, and a part of the seven schools, under India's Ministry of Chemicals and Fertilizers. It is located at Sila Katamur, Changsari in Kamrup district of Assam. The institute offers Masters and Doctoral degrees in pharmaceutical sciences. As an Institute of National Importance it plays an important role in the Human Resource Development for the ever-growing Indian Pharmaceutical industry, which has been in the forefront of India’s science-based industries with wide-ranging capabilities in this important field of drug manufacture.
The current study aims to optimize an RP-HPLC method for the simultaneous estimation of iguratimod (IGU) and methotrexate (MTX) using a quality-by-design (QbD) approach and to validate it in accordance with ICH Q2(R2). The method was developed based on QbD principles using a 4-factor 2-level full-factorial design (24 FFD). The analysis was performed on a ZORBAX Eclipse Plus C18 column (4.6 × 250 mm, 5 μm). The estimation of IGU and MTX was performed using a mobile phase of acetonitrile and orthophosphoric acid buffer (pH 3.0) in gradient mode at a flow rate of 1.0 mL/min. The detection was performed at the isosbestic wavelength of 276 nm. A forced degradation study (acid/base hydrolysis, heat, light, UV radiation) was performed to identify degradation pathways and products. The greenness assessment was done using AGREEprep and AGREE tools. The method was applied to determine the drug content of iguratimod and methotrexate in the Self-Emulsifying Drug Delivery System. The retention times for methotrexate and iguratimod were obtained at 4.4 and 6.9 min, respectively. The developed RP-HPLC method demonstrated linearity over 0.4–6.0 µg/mL (R² = 0.9999), as well as precision, accuracy, selectivity, and robustness. The limit of detection (LOD) and limit of quantification (LOQ) for methotrexate were 12.19 ng/mL and 36.94 ng/mL, respectively. For iguratimod, these limits were 30.24 ng/mL and 91.65 ng/mL, respectively. The developed method was identified as a green method based on AGREEprep (0.63) and AGREE (0.64) scores. The study concludes that the developed method is precise, accurate, simple, robust, and environmentally friendly. This is useful for the simultaneous estimation of iguratimod and methotrexate in lipid-based formulations and other pharmaceutical dosage forms.
Cabazitaxel (CBZ) is a semi-synthetic anti-cancer drug and belongs to BCS class IV category with poor water solubility and low permeability. Its clinical effectiveness is further limited by extensive metabolism mediated by CYP3A4 and CYP2C8 enzymes. Liposome-based drug delivery systems offer a promising strategy to overcome these limitations by enhancing aqueous solubility and bioavailability, while potentially reducing CYP-mediated metabolism. However, recent studies suggest that CBZ may have therapeutic potential for breast cancer. The present study aimed to develop CBZ-loaded drug delivery and enhance cytotoxicity in MCF-7 (breast cancer cells) using TPGS coated liposomes. TPGS-CBZ-Liposomes were prepared by the thin-film hydration method followed by probe ultrasonication. TPGS-CBZ-liposome demonstrated mean particle sizes of 146.8 ± 3.09 nm (PDI 0.035 ± 0.008) and (zeta potential − 3.70 ± 0.68 mV). Compared with pure CBZ, TPGS-CBZ-liposomes showed improved stability and achieved encapsulation efficiency greater than 98
This study addresses the rising incidence of breast cancer by developing advanced therapeutic and analytical solutions. The anticancer potential of biochanin A and quercetin was assessed through in silico molecular docking against hormone-positive breast cancer receptors, with docking scores ranging from − 5.63 to − 6.85 kcal/mol, indicating binding affinities towards hormone positive breast cancer receptors. An analytical quality-by-design (AQbD) approach guided the development of a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous identification and quantification of both compounds. Key method parameters were identified using an Ishikawa fishbone diagram and optimized using a four-factor two-level fractional factorial design. The optimal chromatographic conditions employed a C18 column with a mobile phase of 0.1
Turmeric, a rhizomatous plant, contains curcumin, which is responsible for its yellow hue and various pharmacological activities such as anti-bacterial, anti-inflammatory wound healing, etc. However, curcumin’s pharmacological activities heavily hampered due to its low aqueous solubility (7.80 µg/mL), and poor bioavailability (0.051 µg/L). This investigation explores the possibility of developing topical emulgel formulation based on carbopol and neoteric solvent like camphor menthol based natural hydrophobic deep eutectic solvent. Keeping the camphor-menthol, tween-80, glycerin and water at the constant values of 5
IntroductionHepatic cancer cells regulate reactive oxygen species (ROS) and lipid kinases to promote proliferation and survival. The role of phosphatidylinositol-4-phosphate-5-kinase (PIP5K) in modulating the autophagy–Nrf2 antioxidant pathway remains unclear. In this study, we investigated the impact of PIP5K on the ROS-dependent autophagy–Nrf2 axis using specific isoform inhibitors (PIP5K1A: ISA-201IB; PIP5K1B: IITZ01) and further identified NG-TZ-17 and NG-TZ-20, which are analogs of IITZ01, as novel inhibitors of the PIP5KB isoform.MethodsThe association between PIP5K and the ROS–autophagy–Nrf2 pathway was examined in hepatocellular carcinoma (HCC) tissue samples (n = 36) and hepatic cancer cell lines. In vitro, HepG2 cells (expressing high PIP5K levels) were treated with PIP5K isoform-specific inhibitors, autophagy inhibitors, and Nrf2 inhibitors in the presence of hydrogen peroxide (H2O2). The effects on ROS generation, proliferation, autophagy, antioxidant defense, and apoptosis were assessed using MitoSOX staining, immunofluorescence, and Western blot analysis. In vivo, SCID mice xenografted with GFP-HepG2 cells were treated orally with PIP5K inhibitors (IITZ01 and NG-TZ-17; 50 mg/kg) or sorafenib (60 mg/kg). Tumor progression was monitored through animal imaging, survival analysis, tumor volume measurement, and Western blotting of excised tumors.ResultsPIP5K isoforms, Beclin-1, and Nrf2 expression increased with advancing HCC grade. Autophagy induction upregulated PIP5K isoforms, Nrf2, HO-1, and SOD2, thereby protecting cells from hydrogen peroxide-induced apoptosis. PIP5K inhibition enhanced ROS-mediated apoptosis by suppressing proliferation, autophagy, and Nrf2 signaling. In vivo, NG-TZ-17 and IITZ01 significantly reduced tumor burden, with efficacy comparable to sorafenib (p < 0.001 vs. vehicle control).ConclusionPIP5K isoforms promote hepatic cancer cell proliferation under oxidative stress conditions. Targeting PIP5K sensitizes cells to ROS-mediated apoptosis through modulation of the PI3K/AKT/mTOR and autophagy pathways, highlighting PIP5K as a promising therapeutic target in hepatocellular carcinoma.
