Preparation, characterization and protective effect of pectin/alginate nanoparticles loaded with propolis extract against doxorubicin-induced testicular toxicity.

Doxorubicin (DOX), a potent chemotherapeutic drug, exhibits testicular toxicity via inflammatory and oxidative stress pathways. Accordingly, developing novel therapeutic agents for alleviating DOX toxicity is instantly needed. Propolis extract (PE) has shown versatile biological properties for reproduction improvement. However, PE exhibits poor bioavailability and instability, hindering its applications. Hence, the present study aimed to develop a biocompatible gastric resistance nanoplatform for oral delivery of PE using pectin (PEC) and alginate (ALG) biopolymers, as well as to assess their protective and therapeutic potential against testicular toxicity caused by DOX. The optimized nanoparticles (NPs) fabricated with a 1:1 PEC to ALG mass ratio showed 145.2 nm particle size, -19.3 zeta potential, and 84.8% encapsulation efficiency, along with slow PE release in simulated gastric fluids and great stability for 6 months. Animals treated with DOX showed a significant exacerbation of oxidative stress indicators and a remarkable decrease in semen characteristics. Interestingly, co-administration of PE loaded NPs alleviated DOX-induced toxicity by significantly downregulating interleukin-6 and tumor necrosis factor-alpha and increasing anti-apoptotic Bcl-2 levels. Furthermore, as compared to DOX treated rats, PE loaded PEC/ALG NPs enhanced antioxidant enzyme activities and serum testosterone levels, as well as improved testicular tissue histological status. Moreover, PE loaded PEC/ALG NPs showed good biocompatibility as confirmed by histopathological, biochemical, and hematological assessments. This study reports the fabrication of PE loaded PEC/ALG NPs with promising potential against DOX-induced testicular toxicity, highlighting a novel biocompatible nanoformulation to protect male fertility during chemotherapy.