Hesperidin nanoparticles for prostate cancer therapy: preparation, characterization and cytotoxic activity.

Hesperidin, a phytochemical renowned for its therapeutic effects including anticancer, antioxidant, and anti-inflammatory properties, encounters a significant limitation in its application due to its low bioavailability and restricted solubility in water. To surmount these challenges, we employed a spontaneous emulsification method to produce hesperidin nanoparticles. These nanoparticles, averaging 197.2 ± 2.8 nm, exhibited uniform dispersion (polydispersity index: 0.13), a zeta potential (ZP) of -28 mV, encapsulation efficiency of 84.04 ± 1.3%, and demonstrated stable and controlled release across various environments. Assessment of the nanoemulsions stability revealed remarkably high stability levels. Cytotoxicity evaluations (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-2-H-tetrazolium bromide, neutral red, trypan blue, and lactate dehydrogenase) indicated that cancer cell viability following treatment with hesperidin nanoemulsion was concentration and time-dependent, significantly lower compared to cells treated with free hesperidin. The colony formation assay and cell morphology evaluation further corroborated the heightened efficacy of hesperidin in its nano form compared to the free form. In summary, hesperidin nanoparticles not only exhibited more potent anticancer activity than free hesperidin but also demonstrated high biocompatibility with minimal cytotoxic effects on healthy cells. These findings underscore the potential for further exploration of hesperidin nanoparticles as an adjunctive therapy in prostate cancer therapy.

Mannosylated polylactic-co-glycolic acid (MN-PLGA) nanoparticles induce potent anti-tumor immunity in murine model of breast cancer.

Nanoparticle-based cancer immunotherapy is considered a novel and promising therapeutic strategy aimed at stimulating host immune responses against tumors. To this end, in the present study, mannan-decorated polylactic-co-glycolic acid (PLGA) nanoparticles containing tumor cell lysate (TCL) and poly riboinosinic polycytidylic acid (poly I:C) were used as antigen delivery systems to immunize breast tumor-bearing Balb/c mice. PLGA nanoparticles were fabricated employing a double emulsion solvent evaporation method. The formation of spherical and uniform nanoparticles (NPs) ranging 150-250 nm was detected by field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS). Four nanoformulation were used to treat mice and vaccination-induced immunological responses. Tumor regression and overall survival rate were evaluated in four experimental groups. Tumor cell lysate and poly I:C loaded mannan-decorated nanoparticles (TCL-Poly I:C) NP-MN caused a significant decrease in tumor growth and 2- to 3-fold improvement in survival times of the treated mice. The NPs with or without mannan decoration elicited stronger responses in terms of lymphocyte proliferation, delayed-type hypersensitivity and CD107a expression. Moreover, our data indicated that the production of IFN-γ and IL-2 increased while the production of IL-4 and IL-10 decreased in splenocytes culture supernatants. In the pathological evaluations, we found that necrosis and immune cells infiltration rate in the tumor tissue of the treated mice was elevated, while tumor cellularity and lung metastases significantly decreased in particular in the group that received (TCL-Poly I:C) NP-MN. Altogether, our findings suggested that the mannan-decorated PLGA NPs antigen delivery system had significant anti-tumor effects against the murine model of breast cancer and it could be considered as a step forward to human breast cancer immunotherapy.

Silymarin attenuates mycophenolate mofetil-induced duodenal disorders in rats.

OBJECTIVE: The protective effect of silymarin (SMN) on mycophenolate mofetil (MMF)-induced duodenal disorders was investigated. MATERIALS AND METHODS: Forty-two Wistar rats were assigned to seven groups including control and test groups. The control animals received saline and the test animals were treated with MMF (30 mg/kg, orally) and saline, MMF and SMN (25, 50, and 100 mg/kg, orally), MMF and Celecoxib (CLX, 50 mg/kg, orally), and MMF and SMN plus CLX for 14 consecutive days. The antioxidant status and myeloperoxidase activity were determined and the histopathological examinations on duodenal section also were performed. RESULTS: Biochemical analyses revealed that SMN and CLX individually and in combination therapy could reduce the MMF-increased nitric oxide (NO) content, myeloperoxidase (MPA) activity, and malondialdehyde (MDA) level, while the MMF-reduced level of total thiol molecules (TTM) was increased significantly (p<0.05) by given compounds. Concurrent administration of SMN and CLX resulted in a synergistic effect on the reduction of MDA level and MPO activity. SMN and CLX were able to improve the MMF-induced histopathological damages including the villus atrophy and inflammatory cells infiltration. CONCLUSION: Our data suggest that the MMF-induced duodenal disorders may attribute to the elevated NO and MDA levels and myeloperoxidase activity that resulted in pathological injuries. Moreover, the biochemical alterations and histopathological injuries due to MMF administration were reduced by SMN alone or in combination with CLX indicating its protective effect.

Mycophenolate mofetil alters the antioxidant status in duodenum of rats: Implication for silymarin usage in mycophenolate mofetil-induced gastrointestinal disorders.

Mycophenolate mofetil (MMF) as an immunosuppressive agent is used to prevent graft rejection. One of the adverse effects of long time administration of MMF is the gastrointestinal disorder. This study aimed to investigate the gastroprotective effect of silymarin (SMN) on MMF-induced gastrointestinal (GI) disorders. Twenty-four adult female Wistar rats were assigned into three groups including the control and test groups. The control animals received saline (5 mL kg(-1)) and the test animals were treated with MMF (40 mg kg(-1), orally) and saline, MMF and silymarin (SMN, 50 mg kg(-1), orally) for 14 consecutive days, respectively. To evaluate the GI disorders due to the MMF-induced oxidative stress and subsequently the protective effect of SMN, malondialdehyde (MDA), total thiol molecules (TTM) levels and total anti-oxidant capacity (TAC) were determined. Additionally, histopathological examinations in the duodenal region of small intestine were performed. The MMF-increased level of MDA was reduced by SMN administration, while the MMF-reduced level of TTM increased significantly (p < 0.05) by SMN administration. Histopathological examinations showed the goblet cell reduction and congestion in the MMF-received animals; while SMN was able to improve the MMF-induced goblet cell reduction and congestion. Our data suggest that the MMF-induced GI disorders are characterized by changes in antioxidant status, which presented by the elevation of MDA level and reduction of TTM concentration. Moreover, the improved biochemical alterations and histopathologic damages by SMN indicating its gastroprotective and antioxidant effects.