Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

Abstract

Background Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated. Results NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability. Conclusions Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products. Graphical Abstract

Potential Biological Properties of Lycopene in a Self-Emulsifying Drug Delivery System

“…Lycopene purified from red guava (LPG) was previously characterized by Amorim et al [ 15 ] and Vasconcelos et al [ 17 ]. The parameters of the absorption spectrum determined by the authors corresponded to lycopene 5-Z and a yield of >90% of lycopene per dry extract weight.…”

“…The parameters of the absorption spectrum determined by the authors corresponded to lycopene 5-Z and a yield of >90% of lycopene per dry extract weight. Self-emulsifying drug delivery systems loaded with lycopene purified from red guava (nanoLPG) were produced according to Vasconcelos et al [ 17 ], using sorbitan monostearate, polysorbate 80 and coconut oil. Sorbitan monostearate and polysorbate 80 are non-ionic surfactants that are often used as emulsifiers in the food and cosmetics industries, and in nanostructured systems.…”

“…However, biotechnological applications of lycopene are limited by its instability regarding temperature, oxygen and light, and poor water solubility [ 8 , 13 ]. In this context, a self-emulsifying drug delivery system (SEDDS) loaded with lycopene purified from red guava, named nanoLPG, was developed [ 17 ]. NanoLPG was able to stabilize lycopene at 5 °C for 10 months, while free LPG degraded in the first month of storage.…”

“…NanoLPG was able to stabilize lycopene at 5 °C for 10 months, while free LPG degraded in the first month of storage. It exhibited radical scavenging activity, as shown by ABTS method, and cytotoxic activity against human prostate cancer cells [ 17 ]. Now, the present proposal aims to use nanoLPG to advance knowledge of its antioxidant and anti-inflammatory potential, and to evaluate actions on the cell morphology of the human keratinocyte-lineage HaCaT.…”

Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice

“…The use of nanostructured lipid system circumvents limitations related to the poor lycopene stability, since the carotenoid can be isomerized or degraded when exposed to light, oxygen and temperature variations. In addition, lycopene has low water solubility and poor oral bioavailability [ 35 ]. Another advantage to use the nanostructured lipid system is the possibility to have a stable pharmaceutical formulation containing two bioactive compounds (lycopene and metformin) with distinct water solubility.…”