الفهرس | Only 14 pages are availabe for public view |
Abstract FST (3,7,3′,4′-tetrahydroxyflavone) is a naturally occurring flavonol that has recently come to light as a potential compound able to modulate different pleiotropic pathways. Accordingly, it could exert a plethora of biological effects comprising anti-inflammatory, anti-oxidant, anti-angiogenic, hypoglycemic, hypolipidemic, neuroprotective, senotherapeutic and anti-tumor effects. Hence, it is considered a good candidate for treating numerous diseases. According to Biopharmaceutical Classification System (BCS), FST is a class II drug with low solubility and high permeability. Despite FST’s insightful health –enhancing effects, its oral delivery is still knotty as the low aqueous solubility (less than 1.0 mg/mL) puts a break on its dissolution and oral bioavailability. Therefore, it is imperative to develop suitable drug delivery systems to enhance the oral delivery of FST as well as its therapeutic efficacy. Consequently, the work in this thesis involves the pharmaceutical study on improving the solubility of FST by using a pH modifier tromethamine (Tris) and subsequently an increase in its dissolution rate. It also involves the pharmaceutical study on the potential use of Lipid polymer hybrid nanoparticles (LPHNPs) and polymeric nanoparticles (PNPs) as promising delivery systems for prospective management of severe acute pancreatitis (SAP) and benign prostatic hypertrophy (BPH), respectively. To fulfill these goals, this thesis comprises the following two parts: Part I: Assessing the appropriateness of Fisetin-loaded lipid-polymer hybrid nanoparticles as a prophylactic regimen against severe acute pancreatitis in rats. This part includes the detailed studies on in vitro and in vivo evaluations of different LPHNPs for FST were investigated for management of SAP. Part II: Plausible role of Fisetin-loaded chitosan oligosaccharide nanoparticles in amelioration of benign prostatic hypertrophy. This part includes the detailed studies on in vitro and in vivo evaluations of different FST-loaded COS – tripolyphosphate (TPP) nanoparticles (FST-loaded COS-TPP NPs) were investigated for management of BPH. The results can be summarized as follows: • Encapsulation of FST into a LPHNPs coated with positively charged CT may be potentially considered as an effective way to target several touchpoints which can dampen pancreatic tissue damage, inflammatory cascade, and immune cell recruitment. • Indubitably, the FST-loaded COS-TPP NPs formulation (F2) conferred an astounding in vivo anti-proliferative and protective efficacy against testosterone-induced BPH in rats. |