Belinostat loaded lipid–polymer hybrid nanoparticulate delivery system for breast cancer: improved pharmacokinetics and biodistribution in a tumor model

文献信息

发布日期 2023-10-27
DOI 10.1039/D3TB01317K
影响因子 6.331
作者

Kommera Sai Pradyuth, Shubham A. Salunkhe, Arihant Kumar Singh, Deepak Chitkara, Anupama Mittal


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摘要

Despite various treatment modalities for breast cancer, it still persists as one of the most diagnosed types of cancer in females. The recent investigations in the epigenetics of breast cancer reveal several aberrations in the expression levels of various HDAC enzymes. Henceforth, the present work entails the formulation and characterization of a lipid polymer-based hybrid nanoparticulate (LPN) system for delivery of an epigenetic modulator drug, Belinostat, for its clinical application in breast cancer. The size of Belinostat nanoparticles prepared using a modified hot homogenization method was found to be 166.6 ± 19.95 nm with an encapsulation efficiency of 94.5 ± 5.1%. In vitro characterization for cytotoxicity, cellular uptake, and protein expression in two different breast cancer cells, 4T1 and MCF 7, revealed the superiority of the formulation in comparison with the free drug in MCF 7 cells. Subsequently, the behaviour of the formulation in in vivo settings of healthy and breast cancer xenograft bearing animals was analyzed using pharmacokinetic and biodistribution studies. The results revealed that the formulation demonstrated multi-fold improvement in the pharmacokinetic parameters in tumor bearing animals when compared with the free drug while no difference in pharmacokinetic behaviour was observed in healthy animals indicating the altered biodistribution and specificity of the formulation in breast tumor. This was confirmed by the biodistribution studies exhibiting 20-fold improved uptake and retention of the nanoparticulate formulation in tumor tissues of the animal model at the end of 4 h. Thus, the developed LPN system holds potential to act as a novel drug delivery system for Belinostat with several advantages over the free drug.

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来源期刊

Journal of Materials Chemistry B

Journal of Materials Chemistry B
CiteScore: 12
自引率: 4.9%
年发文量: 831

Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. The journals have a strong history of publishing quality reports of interest to interdisciplinary communities and providing an efficient and rigorous service through peer review and publication. The journals are led by an international team of Editors-in-Chief and Associate Editors who are all active researchers in their fields. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C. More than one Journal of Materials Chemistry journal may be suitable for certain fields and researchers are encouraged to submit their paper to the journal that they feel best fits for their particular article. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive. Antifouling coatings Biocompatible materials Bioelectronics Bioimaging Biomimetics Biomineralisation Bionics Biosensors Diagnostics Drug delivery Gene delivery Immunobiology Nanomedicine Regenerative medicine & Tissue engineering Scaffolds Soft robotics Stem cells Therapeutic devices image block All articles published in Journal of Materials Chemistry B from 2019 onwards will be indexed in MEDLINE®. Articles that primarily focus on providing insight into the underlying science and performance of biomaterials within a biological environment are more suited to our companion journal, Biomaterials Science.

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