Multifaceted evaluation of pyrazole derivative (T4)-chitosan (CS) nanoparticles: Morphology, drug release, and anti-tumor efficacy in a rat model

Abstract

The development of targeted nanotherapeutics has emerged as a pivotal advancement in cancer treatment, aiming to enhance the efficacy and specificity of drug delivery while minimizing systemic toxicity. Due to their biocompatibility and modifiable surface properties, Chitosan-based nanoparticles have shown considerable promise in encapsulating and delivering therapeutic agents directly to tumor sites. This study investigates the potential of 1,5-diary pyrazole derivative (T4)-loaded chitosan (CS) nanoparticles as a novel anticancer agent, evaluating their physical characteristics, in vivo biodistribution, and therapeutic efficacy against cancerous cells. SEM morphological analysis confirmed chitosan-based nanoparticles' smooth, spherical structure, with aggregation patterns typical of high surface energy nanoparticle synthesis. UV-visible spectroscopy and XRD analysis validated the successful incorporation of T4, showing characteristic absorption peaks and indicating a reduction in crystallinity desirable for enhanced drug release. In vivo imaging demonstrated the rapid systemic distribution of T4-CS nanoparticles, essential for delivering therapeutic agents effectively. The cytotoxic potential of T4-CS nanoparticles was significantly higher against cancer cells compared to controls, confirmed by MTT and scratch assays, indicating enhanced anti-cancer activity and potential inhibition of cancer metastasis. Furthermore, histological and gene expression analyses supported the anti-tumor and pro-apoptotic capabilities of T4-CS nanoparticles, showing reduced proliferation markers and inflammatory pathways. Behavioral assessments in rats highlighted the neuroprotective effects of T4-CS nanoparticles against 7,12-dimethyl benzanthracene (DMBA) induced neurotoxicity, suggesting their utility as both anticancer and neuroprotective agents. This multifaceted evaluation underscores the versatility and therapeutic potential of T4-CS nanoparticles, warranting further investigation into their mechanistic effects and clinical applications.

Keywords: Chitosan; Nanoparticles; Pyrazole; Salivary gland tumor; Wistar rat.