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

被引:2
|
作者
Murugan, Raghul [1 ]
Nayak, S. P. Ramya Ranjan [2 ]
Haridevamuthu, B. [2 ]
Priya, D. [3 ]
Rajagopal, Rajakrishnan [4 ]
Pasupuleti, Mukesh [5 ,6 ]
Guru, Ajay [7 ]
Kumaradoss, Kathiravan Muthu [3 ]
Arockiaraj, Jesu [2 ]
机构
[1] Saveetha Inst Med & Tech Sci SIMATS, Saveetha Dent Coll, Dept Pharmacol, Chennai 600077, Tamil Nadu, India
[2] SRM Inst Sci & Technol, Fac Sci & Humanities, Dept Biotechnol, Toxicol & Pharmacol Lab, Kattankulatur 603203, Tamil Nadu, India
[3] SRM Inst Sci & Technol, SRM Coll Pharm, Dept Pharmaceut Chem, Dr APJ Abdul Kalam Res Lab, Kattankulathur 603203, Tamil Nadu, India
[4] King Saud Univ, Coll Sci, Dept Bot & Microbiol, Riyadh 11451, Saudi Arabia
[5] Cent Drug Res Inst CDRI, CSIR, Div Mol Microbiol & Immunol, Sitapur Rd,Sect 10,Janakipuram Extens, Lucknow 226031, Uttar Pradesh, India
[6] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India
[7] Saveetha Dent Coll & Hosp, SIMATS, Dept Cariol, Chennai 600077, Tamil Nadu, India
关键词
Pyrazole; Chitosan; Nanoparticles; Salivary gland tumor; Wistar rat; BREAST-CANCER; CHITOSAN; PHARMACOKINETICS; WARFARIN;
D O I
10.1016/j.ijbiomac.2024.137702
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:10
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