ABSTRACT
BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm , ATP-Binding Cassette Transporters/metabolism , Neoplasms/metabolism , Biological Transport , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/metabolismABSTRACT
Objectives: The objective of the current study was to develop an extended release (XR) tablet formulation for ranolazine using Eudragit L 100-55 and hydroxypropylmethylcellulose (HPMC) K100M in an appropriate composition. Ranolazine, an anti-anginal agent, is mainly used for treating chronic stable angina pectoris. The main advantage of this drug that it exhibits anti-ischemic effect, which was not influenced by either blood pressure or heart rate. Materials and Methods: XR tablets of ranolazine were prepared using variable amounts of Eudragit L 100-55 and HPMC K100M in various proportions as per 32 factorial design by direct compression technique. The amount of polymers with desired sustained drug release was labeled as factors. On other hand, time taken for drug dissolution was labeled as responses (t10%, t50%, t75%, t90%). Results: Nine formulations were obtained as per design, developed, and evaluated for quality control parameters. The obtained results clear that all formulations pass the compendial limits. Data obtained from the dissolution study fitted well to kinetic modeling and kinetic parameters were determined. Polynomial equations were derived for responses and checked for validity. Conclusion: RF5 composed of 31.25 mg of Eudragit L 100-55 and 31.25 mg of HPMC K100M, is the best formulation showing similarity f2: 85.78, f1: 2.32 with the marketed product (RANEXA). Formulation RF5 follows zero order, whereas the release mechanism was found to be non-fickian type (n= 0.65).
