Stability of β-Lapachone upon Exposure to Various Stress Conditions: Resultant Efficacy and Cytotoxicity

Abstract

Even though β-lapachone is a promising compound with antitumor, antiinflammatory, antineoplastic, and wound-healing effects, there are still issues concerning its chemical stability and degradation mechanisms. The objective of this study was to obtain degradation profiles of β-lapachone and evaluate its chemical stability under various stress conditions. Moreover, the correlation between stability and efficacy was evaluated. The degradation study of β-lapachone was performed using heat, acid, base, oxidation, and light conditions. Kinetics and degradation profiles were investigated with HPLC and LC-MS. The stability indicated in the LC method was validated according to the International Conference on Harmonization guidelines. Human dermal fibroblast (HDF) cells were cultured with the standard and its degraded samples in the cellular activity and cytotoxicity test. β-Lapachone was relatively unstable upon exposure to light, and its photodegradation was accelerated with high relative humidity. Three degradants were identified, and their degradation followed zero-order kinetics. It was shown to degrade to phthalic acid under oxidative conditions, and the degradation kinetics were dependent on the concentration of hydrogen peroxide. Two degradation products were identified upon exposure to basic conditions, which followed first-order kinetics. β-Lapachone was relatively stable under acidic and thermal conditions. It increased the synthesis of collagen compared with the control. However, as the contents decreased, the synthesis of collagen also decreased in the photodegraded samples. β-Lapachone did not exert cytotoxic effects at the effective concentration in the cytotoxicity test. Therefore, in order to ensure efficacy and safety, the chemical stability of β-lapachone needs to be controlled carefully while considering instability mechanisms.

Deciphering the Peculiar Behavior of β-Lapachone in Lipid Monolayers and Bilayers

“…β-Lapachone (β-Lap) is a natural compound extracted from the lapacho tree abundantly found in Brazil. It exhibits a large variety of promising pharmacological effects including antiparasitic, anti-inflammatory, antibacterial, , and antitumor. , β-Lapachone has been shown to induce apoptosis in prostate, lung, pancreatic, and breast cancer cells. − Despite its acknowledged therapeutic potential, its poor stability and low water solubility (160 μM) on the one hand and its toxicity at high doses on the other hand have limited its clinical use so far . A clear need has emerged that, as a drug, β-Lap should be properly formulated.…”

“…7−11 Despite its acknowledged therapeutic potential, its poor stability and low water solubility (160 μM) on the one hand and its toxicity at high doses 12 on the other hand have limited its clinical use so far. 13 A clear need has emerged that, as a drug, β-Lap should be properly formulated. Cavalcanti et al 14 reported its encapsulation into unilamellar vesicles consisting of soybean lecithin (containing about 92% PC(18:2/18:2)), cholesterol (CHOL), and stearylamine (SA) in a 7:2:1 molar ratio at pH 7.4.…”