Evaluation of Nanoencapsulated Silymarin in Protecting Testicular Tissue from Immunosuppressive Drug-Induced Oxidative Damage

Abstract

Immunosuppressive chemotherapeutics, in particular cyclophosphamide (CP), are well known to compromise male fertility through oxidative injury of the testicular tissue. Silymarin, a flavonolignan complex extracted from Silybum marianum, is a potent natural antioxidant, but its very poor aqueous solubility limits its clinical usefulness. In the present work we prepared silymarin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles by a modified emulsion solvent-evaporation method and assessed their protective effect against CP-induced testicular damage in adult male albino rats. The nanoparticles displayed a mean hydrodynamic diameter of about 148 nm with a narrow polydispersity (PDI 0.18), a zeta potential of −24.6 mV and an encapsulation efficiency close to 86 %. Forty rats were randomly assigned to four equal groups: control, CP (200 mg/kg, i.p., single dose), CP + free silymarin (100 mg/kg/day, p.o., 14 days), and CP + nanoencapsulated silymarin (Nano-SM, 50 mg/kg/day, p.o., 14 days). Cyclophosphamide produced a marked loss of body and testicular weight, depressed sperm count, motility and viability, raised testicular malondialdehyde and dropped glutathione, superoxide dismutase and catalase. Serum testosterone fell sharply while FSH and LH rose, consistent with primary testicular failure. Free silymarin offered partial recovery, whereas Nano-SM restored most of the measured parameters to near-control values and largely preserved the cytoarchitecture of the seminiferous tubules. The nanoformulation, despite the lower administered dose, was clearly more effective, presumably because of its better intestinal absorption and sustained release. The findings support nanoencapsulated silymarin as a promising adjuvant for protecting fertility in patients receiving immunosuppressive therapy.

Highlights
 Silymarin-loaded PLGA nanoparticles (≈148 nm, EE ≈ 86 %) were prepared and characterized.
 Cyclophosphamide markedly increased testicular MDA and depleted GSH, SOD and CAT.
 Nanoencapsulated silymarin (50 mg/kg) outperformed free silymarin (100 mg/kg).
 Sperm count, motility and serum testosterone were restored toward control values.
 Findings suggest a fertility-sparing role of nano-silymarin during immunosuppressive therapy.