Dasatinib loaded mucoadhesive lecithin-chitosan hybrid nanoparticles for its augmented oral delivery, in-vitro efficacy and safety.

Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS's oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.

Applications of lipid-engineered nanoplatforms in the delivery of various cancer therapeutics to surmount breast cancer.

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.