A quality-by-design approach to develop abemaciclib solid lipid nanoparticles for targeting breast cancer cell lines
Bonnie Chin1, Wei Meng Lim2, Samah Hamed Almurisi3,4
1School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.
Aim:
Abemaciclib (ABE) is an anticancer drug that suffers from low bioavailability and multidrug resistance. This study aims to develop ABE-loaded solid lipid nanoparticles (ABE-SLNs), which will enhance drug solubility and lead to increased cellular uptake and enhanced cytotoxicity when delivering tumor cells.
Methods:
Melt emulsification followed by ultrasonication was used as a method of preparation and Quality-by-Design (QbD) was utilized to optimize ABE-SLNs.
Results:
The optimized ABE-SLNs consist of Precirol-ATO5 as a lipid and Brij-58 as a surfactant. The particle size, PDI value, and zeta potential of the optimized formulation were 170.4 ± 0.49 nm, 0.25 ± 0.014, and -26.4 ± 0.1 mV, respectively. It also showed sustained release behavior and a high entrapment efficiency of 79.96%. ABE-SLNs exhibited enhanced anticancer activity in the MDA-MB-231 and T47D breast cancer cell lines compared to pure ABE. In Caco-2 human colonic cell lines, ABE-SLNs also showed increased cellular uptake.
Conclusion:
The use of QbD to achieve high entrapment efficiency and sustained release in ABE-SLNs, coupled with enhanced cellular uptake and cytotoxicity, represents a novel approach that could set a new standard for nanoparticle-based drug delivery systems.
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