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Dasatinib (DST) is a tyrosine kinase inhibitor with established antiproliferative activity in Triple-negative breast cancer. Conventional treatment strategies with DST have several pitfalls related to the development of resistance, lower cellular uptake and unwanted adverse effects. To address these issues, we have prepared P-selectin-targeted nanoparticles of DST with fucoidan (FUC) as a ligand. Poly lactide-co-glycolide nanoparticles of DST were coated with chitosan (CH) and FUC via electrostatic interaction (DST-CH-FUC-NPs). The mean particle size of 210.36 ± 0.66 nm and a polydispersity index of 0.234 ± 0.013 was observed for DST-CH-FUC-NPs. TEM and FTIR analysis proved CH coating followed by an FUC layer on nanoparticles. DST-CH-FUC-NPs showed a sustained release profile up to 120 h and 2.9 times less hemolytic potential than free DST suspension. DST-CH-FUC-NPs demonstrated 8-fold higher cytotoxicity compared to free DST in MDA-MB-231 cells. Rhodamine-CH-FUC- NPs showed 19 times and 3 times higher cellular uptake than free Rhodamine and Rhodamine-CH-NPs, respectively. DST-CH-FUC-NPs also displayed increased ROS production and mitochondrial membrane potential damage. Apoptosis study revealed a 7.5-fold higher apoptosis index for DST-CH-FUC-NPs than free DST. Subsequently, the DST-CH-FUC-NPs showed increased inhibition of cell migration, where approximately 5 % wound closure was noted. Further, DST-CH-FUC-NPs confirmed higher disruption of lysosomal membrane integrity, which is well correlated with apoptosis results. In addition, developed NPs were nontoxic on MCF 10 A normal cells. All these findings suggest that fabricated DST-CH-FUC-NPs are promising biocompatible carriers for tumor-targeted delivery and enhanced efficacy of dasatinib., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated. Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study. Results: DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC 50 (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC 0-t for the DST-S-SNEDDS group than free DST. Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Breast cancer (BC) is the most extensively accounted malignancy among the women across the globe and is treatable in 70-80% of patients with early-stage, non-metastatic cancer. The current available therapies have been found to be less effective to treat distant organ metastases and advanced breast cancers. The clinical efficacy hugely suffers from chemoresistance, non-specific toxicity, relapse and other associated adverse effects. Furthermore, lack of controlled delivery and effective temporospatial presence of chemotherapeutics has resulted in suboptimal therapeutic response. Nanotechnology based approaches have been widely used over the period as they are nanometric, offer controlled and site-specific drug release along with reduced toxicity, improved half-life, and stability. Lipid-based nanoplatforms have grabbed a tremendous attention for delivering cancer therapeutics as they are cost-effective, scalable and provide better entrapment efficiency. In this review, all the promising applications of lipid-engineered nanotechnological tools for breast cancer will be summarized and discussed. Subsequently, BC therapy achieved with the aid of chemotherapeutics, phytomedicine, genes, peptides, photosensitizers, diagnostic and immunogenic agents etc. will be reviewed and discussed. This review gives tabular information on all the results obtained pertaining to the physicochemical properties of the lipidic nanocarrier, in vitro studies conferring to mechanistic drug release profile, cell viability, cellular apoptosis and in vivo studies referring to cellular internalisation, reduction of tumor volume, PK-PD profile, bioavailability achieved and anti-tumor activity in detail. It also gives complete information on the most relevant clinical trials done on lipidic nanoplatforms over two decades in tabular form. The review highlights the current status and future prospects of lipidic nanoplatforms with streamlined focus on cancer nanotherapeutics., (Copyright © 2022 Elsevier B.V. All rights reserved.)