Lipid-Based Nanocarriers Provide Prolonged Anticancer Activity for Palbociclib: In Vitro and in Vivo Evaluations Publisher



Hassanzadeh P^{1, 2} ; Arbabi E³ ; Rostami F³ Show Affiliations
Source: Acta Medica Iranica Published:2021

Abstract

Breast cancer therapy has remained one of the major healthcare challenges. Based on the critical role of cyclin-dependent kinase 4/6 (CDK 4/6) in cell cycle progression, targeting this signaling appears promising for cancer therapy. Palbociclib, a selective CDKs 4/6 inhibitor, is the first-line treatment for estrogen receptor-positive breast cancer. However, poor absorption or side effects may negatively affect its efficiency. This prompted us to incorporate palbociclib into the nanostructured lipid carriers (NLCs) and evaluate the anticancer effect of the nanoformulation (Pa-NLCs) in in vitro and in vivo models of breast cancer. Pa-NLCs were developed by high-pressure homogenization followed by assessment of the physicochemical characteristics and bioactivities in MCF-7 breast cancer cells and female Wistar rats exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The prepared Pa-NLCs demonstrated suitable physicochemical characteristics, including the controlled release pattern, efficient cellular uptake, and cytotoxicity, while free palbociclib failed to show significant effects. Rats treated with Pa-NLCs exhibited significantly reduced tumor volumes, increased survival rates, and histopathological improvement. Free palbociclib was significantly less efficient than Pa-NLCs. Pa-NLCs, by improving the pharmacological profile of palbociclib and providing longer-lasting effects, can be considered as a promising nanoformulation against breast cancer. © 2021 Tehran University of Medical Sciences. All rights reserved.