Lipid-Nanopotentiated Combinatorial Delivery of Tamoxifen and Sulforaphane: Ex Vivo, In Vivo and Toxicity Studies

Abstract

Aim: This study aims to load tamoxifen (TAM) and sulforaphane (SFN) into nanostructured lipid carriers (NLCs) to enhance their oral delivery. Materials & methods: TAM-SFN-NLCs were prepared using Precirol^® ATO5 and Transcutol^® HP, characterized and evaluated in vitro and ex vivo to assess the drug release profile and intestinal permeability, respectively. In vivo pharmacokinetic and acute toxicity assessment was performed in Wistar rats. Results: Optimized TAM-SFN-NLCs exhibited a particle size of 121.9 ± 6.42 nm and zeta potential of -21.2 ± 2.91 mV. The NLCs enhanced intestinal permeability of TAM and SFN and augmented oral bioavailability of TAM and SFN 5.2-fold and 4.8-fold, respectively. SFN significantly reduced TAM-associated toxicity in vivo. Conclusion: This coencapsulation of a chemotherapeutic agent with a herbal bioactive in NLCs could pave a novel treatment approach against cancer.

Graphical abstract

Keywords::

• acute toxicity study
• box-Behnken design
• breast cancer
• nanostructured lipid carriers
• sulforaphane
• tamoxifen

Financial & competing interests disclosure

The authors are thankful to the Department of Science and Technology, New Delhi, India, for providing fellowship in the form of INSPIRE (DST-INSPIRE) award to B Mangla. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Blinded for review

Experiments on animals were performed as per the approved protocol by Jamia Hamdard (Institutional Animal Ethics Committee [IAEC], Protocol No. 1605). This study was performed as per the approved protocol by Jamia Hamdard (IAEC, Protocol No. 1605) in which female Wistar rats (200–250 g) were housed in a regular laboratory environment with temperature and relative humidity of 25 ± 2°C and 55 ± 5%, respectively.

Additional information

Funding

The authors are thankful to the Department of Science and Technology, New Delhi, India, for providing fellowship in the form of INSPIRE (DST-INSPIRE) award to B Mangla. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.