| Liposomes are formed by the self-assembly of phospholipid bilayers.They are cell-ressembly vesicles,which can simultaneously embed hydrophilic and lipophilic substances,and have functions of transport,protection,controlled release and targeting.However,due to the liposome is easy to aggregate and sensitive to changes in the external environment,which limits the wide application of the liposome.Numerous studies have shown that the gels can load more embedding materials by adjusting its charge and hydrophobic force.Therefore,it is effectively diffusing the solute in the gel to improve its biodegradability and achieve multi-level release.Some scholars have combined liposomes with gels,but most of them are focus on the field of medicinal or materials science such as sustained release of skin,and few studies on the liposome in gels during the digestive tract of human body.It is still unknown whether the gels can better protect the sustained materials releasing embedded in liposomes during the entire digestion.In this study,a novel delivery system liposome in gel(named"lipogels")was constructed to improve the protective effect of trophic factor quercetin,and the cross-linking and in vitro digestion behavior of quercetin lipogel were studied.The main research contents and results are as follws:(1)IPN gels was constructed by chitosan,gelatin and mTG enzyme,and the quercetin-loaded liposomes(-0.72±0.49 mV)was electrostatically interacted with the three-dimensional network structure of IPN gels.The two materials are cross-linked to form a novel carrier system quercetin lipogels,which plays a "double-layer protection" effect on the core quercetin.Two quercetin lipogels with different hardness were constructed,which were 1:1 chitosan and gelatin,10 mg/mL mTG,was 28.67 ± 0.92 N.Chitosan and gelatin ratio was 1:1,and the mTG enzyme concentration was 10 mg/mL,which formed the optimum formula with the hardness 12.65 ± 1.02 N.The encapsulation efficiency of quercetin liposomes was 62.25 ± 1.67%.(2)The crosslinking of IPN gel and quercetin liposome is chemical cross-linking,which generates complex covalent bonds and hydrogen bonds by destroying a series of functional groups.The network structure in the IPN gel has been filled with the vesicle structure of the liposome,and the C=O,P=O bond in the liposome forms an amine group with the ammonia and heterocycle in the IPN gels.High-magnification TEM images showed that quercetin liposomes adsorbed to the gels to form a thick layer,and the gels appeared to be cross-linked with the protein-coated liposomes through the surface.(3)Quercetin lipogels was simulated in oral cavity disruption at 8.7 Hz,and first sheared for 5 s,and then stirred followed by shearing for another 5 s.The results were more in line with real human chewing data.Phosphorus release kinetics of quercetin lipogels with different hardness and quercetin release kinetics showed very low release levels after simulated oral digestion,respectively.Phosphorus release by hard gelatin was 1.65 ± 0.11%,soft gel was 0.61 ± 0.34%.Quercetin release by hard gel was 0.93 ±0.23%and soft gel was 1.02 ± 0.75%.Quercetin liposomes are embedded in network and firmly bound to the gels,and simple mechanical disruption did not effectively release quercetin liposomes.(4)In the in vitro simulated gastrointestinal digestive system,the oral-digested quercetin lipogels particles were mechanically broken by the artificial stomach and the hydrolysis of various enzymes,respectively.Compared with the traditional static digestion(water bath shake model),the artificial stomach can diversify the quercetin lipogels more significantly.Artificial can produce more abundant particle size distribution,which is less than 1 mm.The granules are emptied into the small intestine for further digestion.The release of quercetin in high-hardness lipogels increased from 11.27 ± 1.64%to 73.42 ± 3.49%during gastrointestinal digestion;the release of low-hardness gel increased from 3.65 ±2.51%to 62.98±4.18%.The traditional static digestion model can quickly release quercetin around 61.07 ± 3.57%in 5～10 min.This is due to the injection of pepsin,trypsin and bile salts in the artificial stomach and intestine system,and the traditional digestion is the total amount in the initial digestion.(5)In the in vitro simulated gastrointestinal digestion system,the release of phosphorus from the high-hardness quercetin lipogels increased from 52.07 ± 2.34%to 93.42 ± 4.68%;while soft lipogels was from 70.02± 2.67%to 94.65± 3.19%.Compared with the quercetin liposomes,the lipogels has protective effect comparing with quercetin liposomes by nearly 40%.The results showed that the gels structure plays a key role in the release of quercetin liposomes during gastric digestion.The polypeptide aggregate formed by disulfide bonds and hydrophobic interaction forces can protect the release of quercetin liposomes from the microgel particle structure.The higher hardness quercetin lipogels is more resistant to hydrolysis by pepsin and mechanical extrusion due to higher collagen content.Due to its physical strength and chemical cross-linking with liposomes,the gels play a good protective role in the complex digestion system such as oral cavity breaking,gastric acid,gastric enzyme,trypsin and bile salts.Thus,in the small intestine can be sustained release of the embedded trophic factor-quercetin.The results of this study indicated that the binding of quercetin liposomes to IPN gels is chemical cross-linking.Quercetin lipogels can mimic the release of quercetin liposome in the simulated oral and gastrointestinal digestion system in vitro.The enzyme and bile salts destroy the bimolecular structure of the phospholipid to release quercetin.High-hardness quercetin liposome gels formed more peptides during digestion,mainly through disulfide bonds or hydrophobic interactions,which will increase the cross-linking of peptides(especially disulfides)and decomposes for better controll release. |
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