Despite significant advancements in CNS research, CNS illnesses are the most important and serious cause of mental disability worldwide. These facts show a tremendous unmet demand for effective CNS medications and pharmacotherapy since it accounts for more hospitalizations and extended care than practically all other disorders combined. The site-targeted kinetics of the brain and, pharmacodynamics of CNS effects are determined/regulated by various mechanisms after the dose, including blood-brain barrier (BBB) transport and many other processes. These processes are condition-dependent in terms of their rate and extent because they are dynamically controlled. For effective therapy, drugs should access the CNS "at the right place, time, and concentration". Details on inter-species and inter-condition variances are required to translate target site pharmacokinetics and associated CNS effects between species and illness states, improving CNS therapeutics and drug development. The present review encircles a short discussion about the barriers that affect effective CNS treatment and precisely focuses on the pharmacokinetics aspects of efficient CNS therapeutics.
Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS1000) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS1000-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G2M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS1000-PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS1000-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.
Aim: A novel HPLC method was developed and validated for the simultaneous estimation of paclitaxel (PTX) and baicalein (BAC). Materials & methods: The analytes were resolved in a C18 column using the aqueous solution of formic acid (0.10% v/v) and MeOH (30:70 v/v). Results: The developed method was found to be linear over the concentration ranges 0.039–10 μg/ml and 0.019–10 μg/ml for PTX and BAC, respectively. The lower limits of quantification obtained were 0.042 μg/ml and 0.361 μg/ml for PTX and BAC, respectively. Conclusion: The developed method was found to be precise and accurate as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines, for simultaneous estimation of PTX and BAC, having an application in formulation development and bioanalytical studies.
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