Vol.:(0123456789) 1 3 Drug Delivery and Translational Research https://doi.org/10.1007/s13346-023-01325-8 ORIGINAL ARTICLE Cubic nanoparticles as potential carriers for a natural anticancer drug: development, in vitro and in vivo characterization Randa Abdou 1  · Mariam Mojally 2  · Hany G. Attia 3  · Mohamed Dawoud 4,5 Accepted: 6 March 2023 © Controlled Release Society 2023 Abstract Natural compounds that elicit anticancer properties are of great interest for cancer therapy. However, the low solubility and bioavailability of these compounds limit their use as efficient anticancer drugs. To avoid these drawbacks, incorporation of these compounds into cubic nanoparticles (cubosomes) was carried out. Cubosomes containing bergapten which is a natural anticancer compound isolated from Ficus carica were prepared by the homogenization technique using monoolein and poloxamer. These cubosomes were characterized for size, zeta potential, entrapment efficiency, small angle X-ray diffraction, in vitro release, in vitro cytotoxicity, cellular uptake, and antitumor activity. Particle size of cubosomes was 220 ± 3.6 nm with almost neutral zeta potential − 5 ± 1.2 mV and X-ray measurements confirmed the existence of the cubic structure. Additionally, more than 90% of the natural anticancer drug was entrapped within the cubosomes. A sustained release over 30 h was obtained for these cubosomes. Finally, these cubosomes illustrated higher in vitro cytotoxicity and in vivo tumor inhibition compared with the free natural anticancer compound. Thus, cubosomes could be promising car- riers for enhancement of antitumor efficiency of this natural compound. Keywords Cubic nanoparticles; Bergapten · Natural anticancer drug · Acceptor multilamellar vesicles · In vitro cytotoxicity · In vivo tumor inhibition Introduction Cancer represents a major cause of mortality and is expected to spread annually [1]. Several studies have shown that thyroid cancer ranks the second highest cause of cancer among women in Saudi Arabia [2]. Accordingly, there is an urgent need for effective anticancer drugs. Natural products have been widely used for the treatment of many disorders including cancer [3, 4]. Natural products are a very impor- tant source for the discovery and development of anticancer agents since more than 50% of the current anticancer drugs are developed from natural sources [1]. Plants are considered a rich source of anticancer agents which can be isolated and formulated in a suitable dosage form to overcome the spread of various types of cancers. Despite the high cytotoxic potential of most of these natural products, they exhibit poor aqueous solubility and consequently poor bioavailability which in turn diminishes their therapeutic efficiency [5, 6]. Furthermore, as most anticancer drugs, they mostly exhibit toxic effects due to their non-specific distribution and poor targeting to tumor cells [7–10]. Thus, incorporation of these natural products into different lipid nanoparticles such as nanoemulsion, liposomes, and solid lipid nanoparticles is considered an important strategy to improve their clinical performance. Ficus species were employed in folk medicine for the treatment of many diseases such as gastrointestinal, car- diovascular, respiratory disorders, and cancers [11]. Stud- ies performed on Ficus carica revealed its antioxidant, cancer suppressive, and antiviral effects [12, 13]. Antimi- crobial activity of F. carica extract was reported against * Mohamed Dawoud mzdawoud@uqu.edu.sa 1 Department of Pharmacognosy, Faculty of Pharmacy, Umm Al Qura University, Holy Makkah, Kingdom of Saudi Arabia 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al Qura University, Holy Makkah, Kingdom of Saudi Arabia 3 Department of Pharmacognosy, College of Pharmacy, Najran University, 1988 Najran, Saudi Arabia 4 Department of Pharmaceutics, Faculty of Pharmacy, Umm Al Qura University, Holy Makkah, Kingdom of Saudi Arabia 5 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan-University, Cairo, Egypt