{"title":"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。","authors":"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","doi":"10.1080/1061186X.2025.2519599","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>in vivo</i> 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.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-17"},"PeriodicalIF":4.3000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A novel mucoadhesive phytic acid grafted chitosan nanocarrier encapsulated with cisplatin for site-specific cervical cancer therapy: <i>in vitro</i> and <i>in vivo</i> assessments.\",\"authors\":\"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\",\"doi\":\"10.1080/1061186X.2025.2519599\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>in vivo</i> 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.</p>\",\"PeriodicalId\":15573,\"journal\":{\"name\":\"Journal of Drug Targeting\",\"volume\":\" \",\"pages\":\"1-17\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-06-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Targeting\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1061186X.2025.2519599\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Targeting","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1061186X.2025.2519599","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.