Atorvastatin-loaded cubosome: a repurposed targeted delivery systems for enhanced targeting against breast cancer

Abstract

Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine ¹³¹I to enable the noninvasive visualization and trafficking of the new formulae. The in vivo evaluation in solid tumor bearing mice was conducted for comparing¹³¹I-Atorvastatin solution,¹³¹I-Atorvastatin loaded cubosome and ¹³¹I-Atorvastatin chitosan coated cubosome. The in vivo biodistribution study revealed that tumor radioactivity uptake of ¹³¹I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for ¹³¹I-Atorvastatin chitosan coated cubosome was higher than that of ¹³¹I-Atorvastatin solution and ¹³¹I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.

Keywords:

• Atorvastatin
• cubosome
• radiolabelling
• ¹³¹I
• breast cancer

Ethics approval

Male Swiss Albino mice with tumours that were purchased from The National Research Centre in Egypt were used for the in-vivo biodistribution investigation. The whole animal study adhered to the guidelines and rules set forth by the EAEA's animal ethics committee (210/2021/EAEA). The guidelines established by the European Community are followed by this committee when handling experimental animals.

Authors’ contributions

Eman M El-Marakby: methodology, analysis, writing, editing, data analysis, and methodological interpretation. Hend Fayez: methodology, analysis, and interpreting the data, data analysis and editing. M A Motaleb: methodology, review, and editing. Mai Mansour: methodology, writing, interpretation of findings, scripting, and revising.

Acceptance of participation

All individuals taking part in the study gave their informed consent.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.