Physicochemical characterization, cytotoxic effect and toxicity evaluation of nanostructured lipid carrier loaded with eucalyptol

Abstract

Background Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu. Methods Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model. Results As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of − 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents. Conclusions This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.

Phytochemical Profile, Preliminary Toxicity, and Antioxidant Capacity of the Essential Oils of Myrciaria floribunda (H. West ex Willd.) O. Berg. and Myrcia sylvatica (G. Mey) DC. (Myrtaceae)

“…According to Caldas et al [ 101 ] and Izham et al [ 102 ], 1,8-cineole, the major component of the present sample, showed no indication of toxicity in tests performed with mice. Izham et al [ 102 ] also highlighted that 1,8-cineole had a cytotoxic effect against breast cancer cells without harming the health of the mice subjected to the test.…”

“…According to Caldas et al [ 101 ] and Izham et al [ 102 ], 1,8-cineole, the major component of the present sample, showed no indication of toxicity in tests performed with mice. Izham et al [ 102 ] also highlighted that 1,8-cineole had a cytotoxic effect against breast cancer cells without harming the health of the mice subjected to the test. Elmhalli et al [ 103 ] showed that the EOs of Salvadora persica and Rosmarinus officinalis , which contain 1,8-cineole as a major constituent, have moderate toxicity against nymphs of Ixodes ricinus.…”

Essential oils and their nanoformulations for breast cancer therapy

“…Accumulating evidence suggests that the lipophilicity of EOs is suitable for the encapsulation in NLCs which can enhance their therapeutic efficiency by improving stability, bioavailability, and controlled release (Katopodi & Detsi, 2021). Izham et al (2021) (Nordin et al, 2019). In a subsequent study, the same group further revealed the mechanisms of NLC-citral in a 4T1 mice BC model.…”

Dependence of the Core–Shell Structure on the Lipid Composition of Nanostructured Lipid Carriers: Implications for Drug Carrier Design

“…Most of the recent studies on NLCs are based on their application as drug delivery systems (DDSs) for various functions, such as cancer therapy, − brain targeting, and antioxidant and anti-inflammatory activities. , Moreover, several researchers have reported the potency of NLC in different administration routes such as skin, − oral, parenteral, and intramuscular routes . NLCs have also been reported to exhibit advantages in some nucleic acid-based products such as siRNA from a collagen scaffold as a wound healing material and RNA-based vaccines. , These reports have revealed numerous promising applications of NLCs.…”