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

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2023-11, Vol.11 (45), p.1859-1872
• Main Authors: Pradyuth, Kommera Sai, Salunkhe, Shubham A, Singh, Arihant Kumar, Chitkara, Deepak, Mittal, Anupama
• Format: Article
• Language: English
• Subjects: Animal models; Animal tissues; Animals; Biocompatibility; Biodistribution; Breast cancer; Breast Neoplasms - drug therapy; Cell Line, Tumor; Cytotoxicity; Drug delivery; Drug delivery systems; Epigenetics; Female; Histone deacetylase; Humans; Hybrid systems; Lipids; Nanoparticles; Pharmacokinetics; Polymers; Polymers - metabolism; Tissue Distribution; Tumors; Xenotransplantation
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d3tb01317k

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. A novel lipid polymer hybrid nanoparticulate system to improve the systemic exposure of Belinostat and aid in efficient tumor uptake.