Abstract
Inflammatory cascade plays a pivotal role in the onset and progression of major depressive disorder (MDD) and glioblastoma multiforme (GBM). Therefore, questing natural compounds with anti-inflammatory activity such as diosgenin can act as a double-edged sword targeting cancer and cancer-induced inflammation simultaneously. The blood–brain barrier limits the therapeutic efficiency of the drugs against intracranial pathologies including depression and brain cancers. Encapsulating a drug molecule in lipid nanoparticles can overcome this obstacle. The current study has thus investigated the anticancer and antidepressant effect of Tween 80 (P80) coated stearic acid solid lipid nanoparticles (SLNPs) encapsulating the diosgenin. Physio-chemical characterizations of SLNPs were performed to assess their stability, monodispersity, and entrapment efficiency. In vitro cytotoxic analysis of naked and drug encapsulated SLNPs on U-87 cell line indicated diosgenin IC50 value to be 194.4 μM, while diosgenin encapsulation in nanoparticles slightly decreases the toxicity. Antidepressant effects of encapsulated and non-encapsulated diosgenin were comprehensively evaluated in the concanavalin-A–induced sickness behavior mouse model. Behavior test results indicate that diosgenin and diosgenin encapsulated nanoparticles significantly alleviated anxiety-like and depressive behavior. Diosgenin incorporated SLNPs also improved grooming behavior and social interaction as well as showed normal levels of neutrophils and leukocytes with no toxicity indication. In conclusion, diosgenin and diosgenin encapsulated solid lipid nanoparticles proved successful in decreasing in vitro cancer cell proliferation and improving sickness behavioral phenotype and thus merit further exploration.
Highlights
Depression contributes to poor quality of life in cancer patients, leading to dismal prognosis, increased mortality rate, and risk of suicide (Pinquart and Duberstein, 2010; Linden et al, 2012)
Lecithin and reagent-grade stearic acid (95%) were from SigmaAldrich; polysorbate-80 was from Sigma-Aldrich; isopropanol, phosphate-buffered saline (PBS), HPLC-grade acetonitrile, and diosgenin (93% purity) were from Sigma; formaldehyde solution (37%) was from Riedel-de Haen; extra pure chloroform was from Riedel-de Haen; paraformaldehyde was from Daejung; DMEM (1 × ) + GlutaMAX (1 g/L D-glucose, 110 mg/L sodium pyruvate) was from Gibco; 10% fetal bovine serum was from Gibco; Penstrep was from Gibco; and 0.4% trypan blue was from Gibco
Scanning Electron Microscopy (SEM) images of blank and diosgenin loaded solid lipid nanoparticles were taken at × 20,000 magnifications with size ranging up to 200 nm. (E) Blank solid lipid nanoparticles. (F) Diosgenin incorporated solid lipid nanoparticles. Both blank SLNP and diosgenin incorporated SLNP can be observed from images to be spherical in shape
Summary
Depression contributes to poor quality of life in cancer patients, leading to dismal prognosis, increased mortality rate, and risk of suicide (Pinquart and Duberstein, 2010; Linden et al, 2012). Immune dysregulation is proposed as one of the pivotal components of the bidirectional relationship between cancer and depression. Several signaling pathways have been proposed for the explanation of this bidirectional relationship. Inflammation-induced dysregulation of the kynurenine pathway and changes in IDO1 activity have been documented in cancer and major depressive disorder (MDD) (Raison et al, 2010). Concomitant therapy with currently available antidepressants has been shown to interact with anticancer chemotherapeutic agents and affect treatment outcomes (Grassi et al, 2018). Their use in terminally ill patients is compromised by their slow onset of action and treatment resistance (Block, 2000)
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