RESUMO
Silybin (SLB), an important flavonoid from silymarin, displays significant hepatoprotective, anticancer, antioxidant, and neuroprotective effects. However, its therapeutic efficacy is limited by its low solubility and bioavailability. To address these challenges, we engineered bovine serum albumin (BSA) nanoparticles (NP) loaded with SLB (BSA-NP/SLB) using the coacervation method. BSA-SLB NP exhibited a spherical shape, a mean size of 197 nm, a polydispersity index of 0.275, a zeta potential of -34 mV, and an entrapment efficiency of 67%. X-ray diffraction analysis indicated amorphization of SLB upon encapsulation. Formulation stability was upheld over 180 days. In vitro release assays demonstrated controlled diffusion-erosion release, with approximately 40% SLB released within 0.5 h and 100% over 12 h. Intranasal administration of BSA-NP/SLB in rats improved SLB bioavailability by fourfold compared to free SLB. These findings highlight the promising potential of intranasally administered BSA-NP/SLB as an alternative approach to enhance SLB bioavailability, paving the way for innovative therapeutic applications.
RESUMO
Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.
RESUMO
To verify the influence of ozone (O3) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud's adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O3 injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O3 did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.