Formulation of lipid polymer hybrid nanoparticles of the phytochemical Fisetin and its in vivo assessment against severe acute pancreatitis

Abstract

Fisetin (FST) is a naturally occurring flavonol that has recently emerged as a bioactive phytochemical with an impressive array of biological activities. To the author knowledge, boosting the activity of FST against severe acute pancreatitis (SAP) through a nanostructured delivery system (Nanophytomedicine) has not been achieved before. Thereupon, FST-loaded lipid polymer hybrid nanoparticles (FST-loaded LPHNPs) were prepared through conjoined ultrasonication and double emulsion (w/o/w) techniques. Comprehensive in vitro and in vivo evaluations were conducted. The optimized nanoparticle formula displayed a high entrapment efficiency % of 61.76 ± 1.254%, high loading capacity % of 32.18 ± 0.734, low particle size of 125.39 ± 0.924 nm, low particle size distribution of 0.357 ± 0.012, high zeta potential of + 30.16 ± 1.416 mV, and high mucoadhesive strength of 35.64 ± 0.548%. In addition, it exhibited a sustained in vitro release pattern of FST. In the in vivo study, oral pre-treatment of FST-loaded LPHNPs protected against l-arginine induced SAP and multiple organ injuries in rats compared to both FST alone and plain LPHNPs, as well as the untreated group, proven by both biochemical studies, that included both amylase and lipase activities, and histochemical studies of pancreas, liver, kidney and lungs. Therefore, the study could conclude the potential efficacy of the novel phytopharmaceutical delivery system of FST as a prophylactic regimen for SAP and consequently, associated multiple organ injuries.

Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity

“…Then, the obtained spectra were compared with ASDs and ASIs spectra to determine possible interactions between components. The characteristic absorption bands of FIS appear in the range of 400-1800 cm −1 (Figure 4, black line) and 3200-3600 cm −1 [24,85,86]. The assignments of the FIS bands were collected and compiled in Tables S1 and S2 (Supplementary Materials).…”

“…Files in appropriate formats were prepared using OpenBabel 3.1.1. [86]. The preparation of AChE/BChE and FIS utilized MGLTools 1.5.6 with AutoDock 4.2 (ADT; Scripps Research Institute, La Jolla, San Diego, CA, USA) [87].…”

The development of nanocarriers for natural products

“…Moreover, these FST-loaded LPHNPs significantly reduced inflammatory damage in the liver, kidneys, and lung tissues in an L-arginine-induced acute pancreatitis (SAP) rat model. They enhanced the solubility and efficacy of FST, highlighting their potential in medical applications (Awadeen et al, 2023).…”