Fabrication and Assessment of Diosgenin Encapsulated Stearic Acid Solid Lipid Nanoparticles for Its Anticancer and Antidepressant Effects Using in vitro and in vivo Models

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.

Glioblastoma Multiforme: Probing Solutions to Systemic Toxicity towards High-Dose Chemotherapy and Inflammatory Influence in Resistance against Temozolomide

“…For the preparation of blank SLNPs, the same procedure was followed, excluding the drug. SLNPs were prepared in a horizontal laminar flow hood under sterile conditions to perform the in-vitro cell line studies [ 22 ].…”

Nanoformulation, Chracterization and In vivo Pharmacokinetic Studies of Diosgenin and Emodin-loaded Polymeric Nanoparticles

“…This resulting lower EE for DG in PLGA is attributed due to the strong hydrophobic nature of DG versus ED. However, better EE (56±5%) has been achieved by Khan et al (2022) for DG using the steric acid solid lipid nanoparticle (SLNP) with solvent emulsi cation/evaporation method [10]. The surface zeta potential value attributed to both formulations lay in a range between +25 mV to -25mV which is the indication of some degree of agglomeration due to van der Waals attractions [6].…”

“…Diosgenin (DG) extensively occurred in Dioscoreaceae and Agavaceae family and is the sugar-free (aglycone) hydrolysis product of dioscin which has anti-oxidative, anti-in ammatory, and other pharmacological activities in attenuation and cure of a variety of cancers, cardiovascular diseases, atherosclerosis, and neurological diseases. Despite the potential pharmacological activities, the pharmacokinetic properties and clinical applications of DG have been severely hampered due to its hydrophobic nature, insolubility in water, poor bioavailability, and fast biotransformation in physiological conditions [9][10][11]. Several nanotechnology-based formulations including DG nanocrystals and eight-arm-PEG-DG conjugate nanoparticles demonstrated the improved bioavailability, pharmacokinetic pro le, and enhanced solubility of DG which further signi cantly enhanced therapeutic e ciency to prevent and treatment of arterial and venous thrombus [9].…”

“…The pharmaceutical nanocarriers have a great bene t against present approaches to avoid the bloodbrain barrier and GI tract, to advance the bioavailability of drugs [2,10]. Several biodegradable natural and synthetic polymers such as collagen, brin, chitosan [5], dextran, polylactic acid (PLA), polyglycolic acid (PGA), PLGA [4,7,17,18], polyesters, etc., have been used in drug delivery [19].…”

“…Several nanotechnology-based formulations including DG nanocrystals and eight-arm-PEG-DG conjugate nanoparticles demonstrated the improved bioavailability, pharmacokinetic pro le, and enhanced solubility of DG which further signi cantly enhanced therapeutic e ciency to prevent and treatment of arterial and venous thrombus [9]. Recently, fabricated solid lipid nanoparticles (SLNPs) with DG demonstrated improved antitumor activity of DG against glioma cell lines [10]. Moreover, these SLNPs coated with tween 80 reported signi cant improvements in Con-A-induced sickness behavior in an animal model.…”