一种新型顺铂包封植酸接枝壳聚糖纳米载体用于部位特异性宫颈癌治疗:体外和体内评估。

IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Ivy Saha, Jitu Halder, Tushar Kanti Rajwar, Vineet Kumar Rai, Deepak Pradhan, Ajit Mishra, Ritu Mahanty, Priyanka Dash, Chandan Das, Bibhanwita Satpathy, Salim Manoharadas, Subramanian Palanisamy, Saurjit Mohapatra, Biswakanth Kar, Goutam Ghosh, Goutam Rath
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引用次数: 0

摘要

黏附阴道给药系统为减轻宫颈癌化疗相关的全身毒性提供了一种有前途的策略。金属酶如超氧化物歧化酶2 (SOD2)和过氧化氢酶负责维持癌细胞中的氧化-抗氧化平衡。本研究提出了一种制备顺铂负载植酸交联壳聚糖纳米颗粒(CisPANP)的新方法。CisPANP粒径为278.24±15.64 nm, zeta电位为+39±2.46 mV。纳米颗粒具有较好的缓释性能,24 h内释药量为86.85±6.38%。与未处理的细胞相比,CisPANP显著下调SOD和过氧化氢酶的表达,分别下调3.5倍和1.7倍。CisPANP进一步提高ROS水平,抑制HeLa细胞活力。在EAC细胞系诱导的宫颈癌小鼠模型上评价CisPANP的体内抗癌作用。与纯顺铂相比,顺铂组的肿瘤体积明显减少。CisPANP保留良好,可在阴道内使用顺铂。从组织病理学上看,CisPANP治疗肿瘤周围组织未见明显不良反应,提示其安全性。从本研究的观察结果来看,CisPANP可作为宫颈癌局部治疗的潜在候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel mucoadhesive phytic acid grafted chitosan nanocarrier encapsulated with cisplatin for site-specific cervical cancer therapy: in vitro and in vivo assessments.

A mucoadhesive vaginal drug delivery system offers a promising strategy to mitigate chemotherapy-associated systemic toxicity in cervical cancer (CC). Metalloenzymes like superoxide dismutase 2 (SOD2) and catalase are responsible for maintaining oxidant-antioxidant balance in cancer cells. The present study proposed a new approach to prepare cisplatin-loaded phytic acid crosslinked chitosan nanoparticles (CisPANP). CisPANP exhibited a particle size (PS) of 278.24 ± 15.64 nm with a zeta potential of +39 ± 2.46 mV. The nanoparticles demonstrated a sustained drug release behaviour, i.e. 86.85 ± 6.38% drug was released in 24 h. CisPANP were observed to significantly downregulate the expression of SOD and catalase by 3.5 and 1.7-fold, respectively, as compared to untreated cells. CisPANP further increased ROS level and inhibited HeLa cell viability. The in vivo anti-cancer efficacy of CisPANP was evaluated in EAC cell line-induced CC mice model. The tumour volume in CisPANP was significantly reduced as compared to pure cisplatin (pure Cis). CisPANP was well-retained making Cis available in the vagina. From the histopathology, significant adverse effects were not observed in the surrounding tissue of tumour treated with CisPANP, indicating its safety. From the observations of the present investigation, CisPANP could serve as a potential candidate for the localised treatment of CC.

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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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