Drug Metabolism and Bioanalysis Letters - Volume 18, Issue 1, 2025
Volume 18, Issue 1, 2025
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Recent Advances and Opportunities in Cancer Cell Targeting by Surface Decoration: A Review
More LessRecently, polymeric systems have emerged as the most practical and adaptable delivery method for targeted cancer therapy. Surface functionalization of polymers is one of the delivery methods of targeted drugs. For instance, to increase the selectivity and affinity of polymers for cancer cells, targeting moieties are covalently bonded on their surface. The surface decoration of polymers with a particular tumor-homing ligand, such as an antibody, an antibody fragment, a peptide, an aptamer, a polysaccharide, a saccharide, folic acid, etc. may also increase drug retention and accumulation in the tumor vasculature as well as promote efficient internalization by target tumor cells. This study discusses the recent development of polymeric systems coupled with particular targeting ligands for cancer cell targeting. Additionally, attention is given to the various polymers utilized in cancer therapy and how their surface decoration contributes to cancer cell targeting. We conclude that the surface-modified polymeric system in cancer cell targeting has emerged as a promising platform for safe and effective cancer therapy with the potential to maximize therapeutic efficacy while minimizing systemic side effects.
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Understanding DNA and PARP in Cancer: Tackling Inhibitor Resistance
More LessDeoxyribonucleic acid (DNA) is the crucial molecule that stores and transmits genetic information in living organisms. DNA can incur damage from various sources, necessitating efficient DNA repair mechanisms to maintain genomic stability. Cells employ multiple repair pathways, including single-strand repair and double-strand break repair, each involving specific proteins and enzymes. PARPs play a fundamental role in the repair of DNA to detect damage to DNA and facilitate the repair process. PARPi are drugs that inhibit PARP activity, leading to DNA damage accumulation and cell death, particularly in cancer cells with impairments in DNA repair pathways, such as BRCA1/2 mutations. Additionally, PARPi is promising in treating cancer, offering a targeted therapeutic approach. Resistance to PARP inhibitors continues to be an issue in a major clinical challenge. Mechanisms of resistance include homologous recombination repair restoration, increased drug efflux, and mutations in the PARP1 enzyme. Moreover, to overcome this resistance, researchers are investigating combination therapies, targeted therapies that inhibit complementary DNA repair pathways, and novel agents that can counteract resistance mechanisms. Future perspectives focus on enhancing our understanding of resistance mechanisms, developing more effective and selective PARP inhibitors, and identifying predictive biomarkers for therapy response. These advancements aim to improve the efficacy and durability of PARP inhibitor-based treatments, ultimately leading to better outcomes for cancer patients. This review article focuses on the reasons for the evolution of PARP inhibitors, the mechanisms behind resistance, and new strategies to overcome this resistance.
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Sphingolipids in Cancer: Metabolism, Signaling, and Clinical Implications
More LessAuthors: Sharav A. Desai, Sandip D. Nagare, Vipul P. Patel, Nishant B. Pagare and Tejas C. JangamSphingolipids are bioactive lipids that are essential for cellular functions like signaling, apoptosis, and proliferation. They are also important in the biology of cancer. The complex dynamics of sphingolipid metabolism and its consequences for the advancement of cancer are examined in this review. It highlights the regulatory functions of important enzymes such as ceramide kinase (CERK) and sphingosine kinases (SPHKs) in preserving the equilibrium between sphingosine-1-phosphate (S1P), a pro-survival chemical, and ceramides, which encourage cell death. Tumour growth, metastasis, and treatment resistance are all significantly affected by disturbances in this equilibrium. The review emphasizes the potential of sphingolipids as biomarkers for cancer prognosis and stratification, providing information on the course of the disease and the effectiveness of treatment. Their crucial functions in cellular signalling pathways that affect angiogenesis, immunological evasion, and drug resistance, all of which are linked to cancer, are also reviewed. Their role in the tumor microenvironment further highlights sphingolipids' significance as targets for novel therapeutic approaches. Improved clinical results and personalized cancer treatments are made possible by developments in sphingolipid biology and their potential as biomarkers. This thorough synthesis provides the groundwork for further studies that will use sphingolipid metabolism and signalling to create potent cancer treatments. In the fight against cancer, we can improve therapeutic efficacy and diagnostic accuracy by understanding these intricate relationships.
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A Novel Stability-Indicating HPLC Method with Kinetics Study for the Concurrent Analysis of Anti‐Hypertensive Drug Combination of Atenolol and Indapamide
More LessAuthors: Vibhuti A. Rabadiya, Nehal Shah and Ashok H. AkabariBackgroundStability-indicating methods are essential in pharmaceutical analysis to ensure the efficacy and safety of drugs throughout their shelf life. Atenolol and indapamide, both widely prescribed for hypertension, require robust analytical methods for the detection and quantification of their degradation products. Ensuring their stability is vital to maintaining therapeutic efficacy and safety, necessitating thorough analytical methods. A stability-indicating HPLC method facilitates the assessment of degradation products, contributing significantly to pharmaceutical quality control measures. HPLC is widely preferred due to its high precision, accuracy, and ability to separate complex mixtures effectively.
ObjectiveThe objective of this study was to develop and validate a sensitive and robust stability-indicating HPLC method for simultaneously identifying atenolol and indapamide, even in the presence of their degradation products. The method proposed can enable comprehensive analysis under various stress conditions to monitor the stability and efficacy of the pharmaceutical compounds.
MethodsChromatographic separation was achieved using a Shim-pack C18 column (250 × 4.6 mm i.d., 5 μm), with a mobile phase consisting of acetonitrile, methanol, and phosphate buffer (20:30:50 v/v/v) at pH 3.5. Detection was performed at 254 nm using a photodiode array (PDA) detector, with the column temperature maintained at 30°C. Atenolol and indapamide were subjected to stress testing under acidic, alkaline, oxidative, thermal, and photolytic conditions to evaluate degradation behavior. Specificity was confirmed through peak purity analysis.
ResultsThe developed HPLC method provided excellent resolution, with retention times of atenolol and indapamide being 2.69 minutes and 10.07 minutes, respectively. Both drugs showed sensitivity to acidic, basic, and oxidative conditions, but they remained stable under thermal and photolytic stress. Degradation kinetics under acidic, alkaline, and oxidative conditions demonstrated the method's effectiveness in identifying degradation pathways and products. No interference from excipients or degradation products was observed, confirming the method's specificity. The technique achieved larger eco-analytical scale (78.5) and AGREE (0.59) scores compared to previously reported methods, indicating reduced environmental impact through eco-friendly solvents, minimized waste, and improved energy efficiency.
ConclusionThe developed stability-indicating HPLC method successfully identified and quantified atenolol and indapamide in the presence of degradation products. It offered high specificity, precision, and robustness, making it ideal for routine pharmaceutical analysis. The method distinguished between the active drugs and degradation products under various stress conditions, ensuring the long-term stability and efficacy of atenolol and indapamide formulations. These findings can significantly contribute to pharmaceutical quality control, ensuring drugs’ safety and effectiveness.
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Bioanalytical Method Development and Validation for the Estimation of Metformin and Vildagliptin in K3EDTA Human Plasma Using HPLC-ESI-MS/MS
More LessAuthors: Binit Patel, Shalin Parikh, Ravi Patel, Khushbu Patel, Pinak Patel, Pravinkumar Darji, Archita Patel and Samir PatelObjectiveA unique liquid chromatography-tendon mass spectrometric technique for the determination of metformin and vildagliptin in K3EDTA human plasma was developed and verified as per the USFDA guidelines of bioanalysis.
MethodsThe chromatographic separation was achieved using a Cosmosil CN (150 x 4.6 mm, 5 µm) column with an isocratic elution pattern using 10 mM ammonium formate (pH 5.0) and methanol in the ratio of 30:70 v/v as a mobile phase. A mass spectrometer coupled with an electrospray ionization (ESI) source operating in the positive ion was used for detection. Data were obtained in the multi-reaction monitoring (MRM) acquisition mode. Metformin D6 and vildagliptin D7 were used as internal standards, with the flow rate at 1.0 mL/min throughout the experiment. The drugs were extracted by solid phase extraction (SPE) packed with Phenomenex Strata-X. Extraction of the drug was achieved using methanol: 5 mM sodium lauryl sulphate solvent mixture in equal proportions.
ResultsThe retention time for MET and VLG were 3.2 and 3.8 minutes individually. The drugs were extracted by SPE with good recovery of 89.44% and 87.57% for metformin and ISTD and 92.26% and 89.58% for vildagliptin and ISTD, respectively. Sample elution was performed using solid phase extraction (SPE), and this technique produced very pure extracts with good recovery rates. A liner calibration curve was found in the range of 0.5-400 ng/mL for MET and 0.2-160 ng/mL for VLG with a correlation coefficient r2 > 0.99.
ConclusionThe aforementioned technique is reliable and effective for monitoring bioequivalence investigations in human participants.
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