Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines

Md Khalid Anwer; Farhat Fatima; Mohammed Muqtader Ahmed; Mohammed F Aldawsari; Amer S Alali; Mohd Abul Kalam; Aws Alshamsan; Musaed Alkholief; Abdul Malik; Alanazi Az; Ramadan Al-Shdefat

doi:10.1016/j.jsps.2022.03.019

Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines

Saudi Pharm J. 2022 Jun;30(6):726-734. doi: 10.1016/j.jsps.2022.03.019. Epub 2022 Apr 6.

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.
² Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
⁴ Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid, Jordan.

Abstract

Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3-842.2 nm), PDI (0.448-0.853), ζP (-8.21 to -19.7 mV), %EE (48.45-79.36%) and %DL (7.69-19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.

Keywords: Abemaciclib; Biocompatibility; Cytotoxicity; Ethylcellulose; Nanosponges.