Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

Abstract

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as “flavonosome”. Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA–phosphatidylcholine) through four different methods of synthesis – bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug–carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA–phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of −39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

Antioxidant, α‐amylase and α‐glucosidase activity of various solvent fractions of I. obliquus and the preventive role of active fraction against H2O2 induced damage in hepatic L02 cells as fungisome

“…In comparison with the other spectra, marked changes were observed in EAPC, which confirmed the successful formation of Fungisome. The results were in accordance with the IR spectra of previously reported phytosomes (Karthivashan et al., 2016; El‐Fattah et al., 2017; Rathee & Kamboj, 2018; Telange et al., 2017).…”

“…In this study, the ς potential value of EAPC comes under ±40 to ±60 mV colloid stability, which indicates the good stability condition (Mahajan & Ramana, 2014). Liposome that possess zeta potential <−30 mV are considered as the optimum formulation (Hadian, Sahari, Moghimi, & Barzegar, 2014; Karthivashan et al., 2016). Generally, the suspensions with high ς potential values, either positive or negative were electrically stable due to the high electrostatic repulsion forces among the particles whereas the low ς potential values tend to coagulate/aggregate results in poor stability (Hadian et al., 2014).…”

“…The synthesis of active solvent fractions of IO phytosome was prepared according to the previous literature (Karthivashan et al., 2016). Briefly, the ethyl acetate fraction of IO and soy‐derived phosphatidyl cholines (PC) was dissolved in dichloromethane (DCM), 1:2 as milligram ratio in a 50 mL round bottomed flask and sonicated at 40 °C for 30 min.…”

“…Thus, in this research we aimed to determine the bioactive solvent fractions of IO and increase its bioavailability via synthesizing it as a phospholipid complex (fungisome). This attempt will enhance the bioavailability and absorption of hydrophilic constituents present in the active fraction that retards diffusion through lipid membranes (Ghanbarzadeh, Babazadeh, & Hamishehkar, 2016; Karthivashan, Masarudin, Kura, Abas, & Fakurazi, 2016). As the largest parenchymal organ of the human body, the liver is an important organ for glucose and lipid metabolism in the body and one of the main target organs for insulin action.…”

<p>Novel Drug Delivery Systems for Loading of Natural Plant Extracts and Their Biomedical Applications</p>

“…After checking for many physicochemical properties, they suggested that this three-in-one flavonosome with sustained activity is a good candidate as an antioxidant, hepatoprotective, and heat supplement agent. 169 More examples of herbal loaded NE are presented in Table 1. [170][171][172][173][174][175] Self Nanoemulsifying Drug Delivery System (SNEDDS) SNEDDS is a lipid-based anhydrous isotropic mixture of oil, surfactant(s) and cosurfactant(s) with a particle size of 20-200 nm ( Figure 11).…”