Title : Fabrication of anti-EGFR-grafted lipid nanoparticles for effective delivery of anti-cancer drug: A multifaceted approach combating breast cancer
Abstract:
Background: Cabazitaxel, US-FDA synthetic taxane has been highly recognized in treatment of metastatic prostate cancer. Clinical evidences show the drug also exhibit potency in treatment of breast cancer. Despite numerous advantages this drug undergoes various challenges like low solubility, poor drug permeation, rapid plasma clearance.
Objectives: This study focuses on designing nanotechnology based targeted drug delivery system for repurposing of drug and reducing its challenges for the treatment of breast cancer.
Methods: The work involve preparation and optimization of solid lipid nanoparticle using solvent evaporation method. This formulation was further modified using chitosan for enhancing stability and further coated with EGFR for targeted delivery.
Results: Characterization studies revealed that the SLNs had a particle size of 220±0.75 nm with a drug entrapment efficiency of 89.42±0.35%. On comparison with the marketed formulation the studies reveal that invitro release of the formulation offered a higher drug release rate at pH 5.6 (88.89%) than at pH 7.4 .The lipidic formulation showed lower IC50,values in breast cancer cell lines MDA-MB231 in comparison with the plain and marketed formulations. The 3D model spheroids-based studies have also confirmed that formulation exhibits more than 7 times more efficacy than plain cabazitaxel and 5 times than marketed formulations. Moreover, hemolysis studies revealed the blood-compatible nature of the nanoconjugate, indicating its safety for intravenous administration Pharmacokinetic studies showed that the developed system offered higher bioavailability and decreased drug clearance from the system compared to the plain drug.
Conclusion: The comprehensive data reveals that EGFR-targeted nanoformulation significantly improved the safety and efficacy of cabazitaxel in combating breast cancer.
