| BackgroundFlavonoids are abundantly available in nature and they are well-acceptable bioactive compounds.Flavonoids have been reported to have many health benefits and anti-disease activities.At the same time,it was also verified that flavonoids are unstable at physiological conditions,thus it may show limited bioavailability and bioactivity in biological models.However,plenty of efforts have been invested to improve and/or preserve the bioactivity of natural compounds.Among them,the encapsulation of natural products using a nanoliposomal drug delivery system is a promising approach.Studies reported on the liposomal delivery of natural products are mostly designed for the intravenous route.Moreover,most of the available reports on oral delivery of natural compounds using the liposomal system are superficial and fractional that demand more in-depth investigation and exploration.To date,no work has been reported on the gastrointestinal(GI)delivery of anthocyanin and neohesperidin through the liposomal system and controlled release profiling and bioactivity retention ability of liposome in the GI tract.On the other hand,liposome itself is unstable at gastric p H and could be undergone to oxidative degradation during storage.The improvement of liposomal stability is another challenging issue if liposomes are considered for the oral delivery of flavonoids.Furthermore,the chemical structure of flavonoids can also alter the physicochemical characteristics of liposomal vesicles that might also affect its stability.The application of surface modification approach through layer-by-layer(LBL)electrostatic interaction is a promising way to improve the stability of nanoparticle at physiological conditions and prolong the half-life in blood circulation.For this purpose,charged natural biopolymers(e.g.polysaccharides,proteins)can be employed to alter the surface characteristics of the existing carrier system.Depending upon the physicochemical features of the polymer,the stability and functionality of a modified carrier can be varied.Thus,it is very important to choose the suitable polymer,understanding the binding mechanism,and study the surface saturation behavior during optimization of polymer concentration.ObjectivesThis study aimed to develop a stabilized and functionalized nanoliposomal system to improve the stability,controlled release features,and bioactivity retention of neohesperidin(lipophilic)and pelargonidin-3-O-glucoside(hydrophilic anthocyanin)in a biological system.For this purpose,a nanoliposomal vesicular system has been developed using thin-film hydration and probe sonication approach.To improve the stability and functionality of nanoliposome,natural biopolymers,i.e.CH and P has been subsequently bonded over the particle surface using LBL electrostatic approach.Neohesperidin(lipophilic)and pelargonidin-3-O-glucoside(hydrophilic)were the model flavonoids used in this study.The particle characterization was performed using dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FTIR),high performance liquid chromatography(HPLC),transmission electron microscopy(TEM),and differential scanning calorimetry(DSC).Major findings1.The DLS results exhibited that the particle size of NL,CH-NL,and P-CH-NL were varied from 70.42-89.94,191.1-251.23,and 225.2-444.77 ?m,respectively.While the zeta potential of these carriers was-24.4 to-31.40,+20.1 to +23.47,and-19.2 to-23.1 m V,respectively.The increase of particle size and change of zeta potential confirmed the proper binding of biopolymers over the carrier surface.The FTIR results also proved the successful deposition of CH and then P layer onto NL.According to DSC results,the coating of a biopolymer improved the thermal stability of nanoliposomes.TEM imaging analysis showed that nanoliposomal vesicles were predominantly unilamellar and spheric form.2.The in vitro digestion study revealed that the conjugation of P and CH over NL significantly improved the controlled release of NH.The NH release kinetics from P-CH-NL followed the anomalous diffusion mechanism.Conjugated NH-loaded carriers represented greater efficiency in preserving the DPPH and FRAP activity,while P-CH-NH-NL possessed maximum ABTS antioxidant activity.Biopolymer conjugation improved the cellular uptake,while P-CH-NL was the most efficient carrier exhibited the highest deposition of Rh123 into Caco-2 cells.In vitro cytotoxicity study exhibited greater protection of Caco-2 cells by conjugated NL carriers from AA-induced cytotoxicity and ROS formation.3.P-CH-NL had better physical stability to different salt concentrations and p H conditions as well as greater P3 G retention efficiency under oxidative,thermal,and UV-light condition than that of CH-NL and NL.Nanoliposomal carriers were more stable at refrigerated conditions and ensured good retention of P3G(>96%).In vitro mucoadhesion study revealed that CH-P3G-NL showed better mucin adsorption efficiency(59.72%).CH-NL had less turbidity indicating better stability to serum,and P-CH-NL showed a minimum release ratio of P3 G suggesting better protection of P3 G at serum.4.Both in enzymatic and non-enzymatic digestion,functionalized nanoliposomes were more efficient in P3 G retention than NL.P3 G release from nanoliposomal carriers followed the Fickian diffusion mechanism both in food simulants and digestion models.Digested nanoliposomes exhibited P3 G release-based antioxidant activity,in which P-CH-NL revealed higher scavenging properties at SIF and SCF stages.Furthermore,the antidiabetic potential of digested nanoliposomes was significantly(P <0.05)higher than that of non-digested samples.It was also found that functionalized nanoliposomes can possess better antidiabetic potential during the digestion process than the traditional nanoliposome.5.Taken together,the developed functionalized nanoliposome is promising for colon-targeted delivery of both hydrophilic and lipophilic compounds with a controlled-release functionality and it may also be useful in functional foods or beverages. |
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