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Fisetin (FST), a naturally occurring bioactive phytochemical with illustrious pharmacological activities, has appeared as a potential compound with antioxidant, anti-inflammatory as well as anti-proliferative activity. Benign prostatic hypertrophy is one of the most common urinary diseases affecting men mostly after the age of 50. It is reported that Fisetin can ameliorate prostatic cancer. To the best of our knowledge, there is no issued information yet concerning the formulation of FST as chitosan oligosaccharide-TPP (COS-TPP) nanoparticles (NPs) as a protective regimen against benign prostatic hypertrophy (BPH). Hence, FST-loaded COS-TPP NPs were successfully prepared to evaluate their efficacy as a prophylactic regimen against BPH. Comprehensive in vitroand in vivoevaluations were conducted. The optimized COS-TPP NPs formula revealed low particle size of 133.06 ± 1.35 nm, low particle size distribution of 0.32 ± 0.18, high zeta potential of +33.95 ± 0.56 mV, high entrapment efficiency % of 63.04 ± 2.33 %, and high mucoadhesive strength of 47.55 ± 1.84 %. Moreover, it displayed a sustained in vitrorelease pattern of FST. Scrupulous in vivoassessment comprising histopathology, prostatic index, sperm count, and immunohistochemistry of orally administered FST-loaded COS-TPP NPs formula was performed to scout out its momentous activity against testosterone induced BPH in rats. The results elicited a prodigious in vivoanti-proliferative and protective efficacy compared to both FST alone and plain COS-TPP NPs. For the first time, COS was found to synergize the effect of FST in the prevention of prostatic hyperplasia. In conclusion, this novel phytopharmaceutical delivery system could be considered as a prospective promising one for management of BPH.

Hesperidin (Hsd), a promising bioactive phytomedicine, possesses a wound-healing activity. However, its poor solubility necessitates frequent topical application of high doses. Hence, this study aimed to prepare and characterize Hsd-loaded hybrid nanoparticles (Hsd-HNPs), followed by surface coating with chitosan (CS) to overcome such obstacles.