Digestion Of Triglycerides Research Articles

Interfacial behaviour of human bile and its substitution for in vitro lipolysis studies

This study examined the interfacial evolution of individual bile salts (BSs) and their blends with phosphatidylcholine (BS/PC) to simulate the complex behaviour of human bile (HB) during lipolysis at the triglyceride/water interface. Using adsorption and desorption cycles, mimicking exposure to small intestinal fluids, we demonstrate that the interfacial behaviour of HB can be replicated using simple mixtures of BSs and PC. Interfacial tension (IFT) measurements after lipolysis and desorption showed no significant differences (P > 0.05) between HB samples and BS/PC mixtures across the total BS concentrations analysed (2.23–7.81 mM). However, individual BSs without PC yielded significantly different IFT results (P < 0.01) compared to HB, highlighting the importance of phospholipids. Dilatation rheology further emphasised the need for accurate phospholipid representation in bile models. Our results suggest that phospholipids in HB and BS/PC systems enhance resistance to desorption, potentially affecting lipolysis. This is important, as current in vitro digestion models often replicate only intestinal BS concentrations to mimic the behaviour HB in the intestinal lumen. Furthermore, the specific composition of BSs in HB appears less critical than the overall BS and phospholipid content, suggesting that the kinetics of triglyceride digestion is influenced by the combined luminal concentrations of these components. These findings have significant implications for understanding the role of bile in digestion and offer insights for designing more accurate in vitro models to study food emulsions and lipid-based delivery systems.

The effect of citral loading and fatty acid distribution on the oleogels: Physicochemical properties and in vitro digestion

Oleogels containing bioactive substances such as citral (CT) are used as functional food ingredients. However, little information is available on the influence of different oleogel network structure caused by CT addition and fatty acid distribution on its digestion behavior. Coconut oil, palm oil, high oleic peanut oil, safflower seed oil, and perilla seed oil were used in this study. The results showed that perilla seed oil-CT-based oleogels had the highest oil-holding capacity (99.03 ± 0.3), whereas CT addition higher than 10 wt% could lead to the morphology collapse of oleogels. Physical and thermodynamic analyses revealed that CT could reduce oleogel hardness and higher unsaturated fatty acid content is more likely to form oleogel with stable and tight crystalline network. Moreover, the dense structure of oleogels hinders the contact between oleogels and lipase, thus weakening triglyceride digestion. These findings provide valuable insights into the design of oleogels loading with CT.

Characterizations on a GRAS Electrospun Lipid-Polymer Composite Loaded with Tetrahydrocurcumin.

Electrospun/sprayed fiber films and nanoparticles were broadly studied as encapsulation techniques for bioactive compounds. Nevertheless, many of them involved using non-volatile toxic solvents or non-biodegradable polymers that were not suitable for oral consumption, thus rather limiting their application. In this research, a novel electrospun lipid-polymer composite (ELPC) was fabricated with whole generally recognized as safe (GRAS) materials including gelatin, medium chain triglyceride (MCT) and lecithin. A water-insoluble bioactive compound, tetrahydrocurcumin (TC), was encapsulated in the ELPC to enhance its delivery. Confocal laser scanning microscopy (CLSM) was utilized to examine the morphology of this ELPC and found that it was in a status between electrospun fibers and electrosprayed particles. It was able to form self-assembled emulsions (droplets visualized by CLSM) to deliver active compounds. In addition, this gelatin-based ELPC self-assembled emulsion was able to form a special emulsion gel. CLSM observation of this gel displayed that the lipophilic contents of the ELPC were encapsulated within the cluster of the hydrophilic gelatin gel network. The FTIR spectrum of the TC-loaded ELPC did not show the fingerprint pattern of crystalline TC, while it displayed the aliphatic hydrocarbon stretches from MCT and lecithin. The dissolution experiment demonstrated a relatively linear release profile of TC from the ELPC. The lipid digestion assay displayed a rapid digestion of triglycerides in the first 3-6 min, with a high extent of lipolysis. A Caco-2 intestinal monolayer transport study was performed. The ELPC delivered more TC in the upward direction than downwards. MTT study results did not report cytotoxicity for both pure TC and the ELPC-encapsulated TC under 15 μg/mL. Caco-2 cellular uptake was visualized by CLSM and semi-quantified to estimate the accumulation rate of TC in the cells over time.

The bile salt/phospholipid ratio determines the extent of in vitro intestinal lipolysis of triglycerides: Interfacial and emulsion studies

This study focused on the protein-stabilised triglyceride (TG)/water interfaces and oil-in-water emulsions, and explored the influence of varying molar ratios of bile salts (BSs) and phospholipids (PLs) on the intestinal lipolysis of TGs. The presence of these two major groups of biosurfactants delivered with human bile to the physiological environment of intestinal digestion was replicated in our experiments by using mixtures of individual BSs and PLs under in vitro small intestinal lipolysis conditions. Conducted initially, retrospective analysis of available scientific literature revealed that an average molar ratio of 9:4 for BSs to PLs (BS/PL) can be considered physiological in the postprandial adult human small intestine. Our experimental data showed that combining BSs and PLs synergistically enhanced interfacial activity, substantially reducing oil–water interfacial tension (IFT) during interfacial lipolysis experiments with pancreatic lipase, especially at the BS/PL–9:4 ratio. Other BS/PL molar proportions (BS/PL–6.5:6.5 and BS/PL–4:9) and an equimolar amount of BSs (BS–13) followed in IFT reduction efficiency, while using PLs alone as biosurfactants was the least efficient. In the following emulsion lipolysis experiments, BS/PL–9:4 outperformed other BS/PL mixtures in terms of enhancing the TG digestion extent. The degree of TG conversion and the desorption efficiency of interfacial material post-lipolysis correlated directly with the BS/PL ratio, decreasing as the PL proportion increased. In conclusion, this study highlights the crucial role of biliary PLs, alongside BSs, in replicating the physiological function of bile in intestinal lipolysis of emulsified TGs. Our results showed different contributions of PLs and BSs to lipolysis, strongly suggesting that any future in vitro studies aiming to simulate the human digestion conditions should take into account the impact of biliary PLs – not just BSs – to accurately mimic the physiological role of bile in intestinal lipolysis. This is particularly crucial given the fact that existing in vitro digestion protocols typically focus solely on applying specific concentrations and/or compositions of BSs to simulate the action of human bile during intestinal digestion, while overlooking the presence and concentration of biliary PLs under physiological gut conditions.

Comparative study on the in vitro digestion of different lipids in starch-based Pickering emulsions

Starch-based Pickering stabilizer has attracted more attentions due to its health-friendly attribute. Lipid digestion in Pickering emulsion is the key to its delivery ability for active substances. Herein, in vitro oral-gastric-intestinal digestions of Pickering emulsions stabilized by starch particles with different oil phases (e.g., coconut, corn, olive, and sunflower oils) were investigated. The highest rate of lipid digestion was coconut oil (25.71 %), followed by olive (12.64 %), corn (11.16 %), and sunflower (8.99 %) oils. The lipid digestibility was influenced by saturation of fatty acids: coconut (91.41 %)>olive (16.58 %)>corn (14.63 %)>sunflower (10.85 %) oils. The increase of starch concentration (0.5 % – 4.0 %, w/w) had positive effects, while the increase of oil fraction (25 % – 70 %, v/v) had negative impacts on free fatty acid release due to the formation of different initial droplet sizes. The microstructures observed using confocal laser scanning microscope indicated that starch-based Pickering emulsion possessed super stability against oral and gastric digestions, which made it a superior delivery system for lipophilic active substances under severe gastric environment. These results may promote the design of functional food emulsions stabilized by starch particles which can regulate digestion of triglycerides.

Long Short-Term Memory-Based Multiomics Reveal Lactobacillus casei-Derived Postbiotics Inhibiting Lipids Digestion via Mediating the Upregulation of α-Helices in Lipase.

The antiobesity function of probiotics has been declared, while the application in high-risk patients and coding side effect has focused attention to postbiotics. This investigation profiles the mechanism of postbiotics affecting lipid digestion at molecular level, and establishes a momentous foundation for the clinical application of postbiotics in obesity suppression. An operational framework for butter digestion is constructed to collect the digests in the intestine at 0, 40, 80, and 120min with various postbiotics supplement. A total of 227 lipids and 414 metabolites are detected by pseudo-targeted lipidomics integrated with the long short-term memory-based metabolomics, and the triacylglycerol (TG, from 134.1 to 184.7mg kg-1 ) and diacylglycerol (DG, from 4.2 to 8.4mgkg-1 ) are identified as significantly different lipids with or without postbiotics supplement. A total of eight substances related to the inhibition of gastric lipase and pancreatic lipase are screened through the molecular simulation computation in silicon and enzymatic reaction kinetics, and thus curtailing the bioaccessibility of lipids. Lactobacillus casei JCM1134-derived postbiotics propel the structure of lipase to aggregate by increasing the α-helix, and thus hampering the digestion of triglycerides through noncompetitive inhibition.

Design, Synthesis, Molecular Modelling and in Vitro Evaluation of Indolyl Ketohydrazide-Hydrazone Analogs as Potential Pancreatic Lipase Inhibitors.

Inhibition of Pancreatic lipase (PL) is considered to be a promising target for the management of obesity, owing to its crucial role in the digestion of dietary triglycerides. A series of 31 indolyl ketohydrazide-hydrazone analogs (5 aa-cm) were designed, synthesized and evaluated for their PL inhibitory potential. The analogs were designed using molecular modelling studies. The designed analogs were then synthesized by condensation of indolyl oxoacetohydrazide with various substituted benzaldehydes. All the synthesized analogs showed PL inhibitory activity in the range of 4.13-48.35 μM, as compared with orlistat (0.86±0.09 μM). The most potent analog 5 bi (IC50 =4.13±0.95 μM) was found to show a competitive type of inhibition with Ki value of 0.725 μM. Additionally, the molecular docking study proved the binding of analog 5 bi at the active site of PL (PDB ID: 1LPB) with MolDock score of -141.279 kcal/mol. It also exhibited various interactions with the key amino acids namely Phe77, Phe215, Tyr114, Ser152, Arg256, His263, etc. Furthermore, the protein-ligand complex of analog 5 bi was found to be stable in molecular dynamics simulation for 100 ns with RMSD of less than 3.2 and 4 Å for the protein and ligand, respectively. The current work hereby provides a basis for the potential role of indolyl ketohydrazide-hydrazone analogs in PL inhibition and further optimization could result in the generation of new leads as anti-obesity agents.

Anti-Lipase and Antioxidant Activities of the Selected Plant Materials

Pancreatic lipase plays an important role in the efficient digestion of triglycerides. Its action on lipids produces fatty acids, accumulating in excess into various tissues leading to dyslipidaemia and associated co-morbidities. Thus, inhibition of pancreatic lipase is one of the preferable ways to prevent such conditions. The present study is aimed to evaluate the anti-lipase and antioxidant activities of the leaves of Magnifera indica L. (mango), Psidium guajava L. (guava) and Moringa olifera L. (moringa), and fresh rhizomes of Zingiber officinale R. (ginger), Curcuma longa L. (turmeric), and Curcuma amada R. (mango ginger). The selected samples were dehydrated, powdered, and extracted using absolute ethanol. The extracts were analysed for total phenols, flavonoids, DPPH radical scavenging activity and anti-lipase activity. Among the selected leaves, mango leaves had the highest total phenolic content (6300 mg GAE /100 g), total flavonoid content (6930 mg RE /100 g) and highest DPPH radical scavenging activity (14497.3 mgTE /100 g). The highest lipase inhibition (89.07%) was observed in guava leaves. In rhizomes, turmeric contained the highest total phenolic content (6570 mg GAE /100 g) and flavonoid content (14760 mg RE /100 g). Mango ginger possessed the highest DPPH radical scavenging activity of 9038.7 mg TE /100 g and lipase inhibition of 44.83%. The study concludes that guava leaves and mango ginger possess the highest anti-lipase activity among the selected leaves and rhizomes.

Features of nutrition in exocrine pancreatic insufficiency and metabolic syndrome

The review presents literature data on the importance of nutritional goals, which include ensuring sufficient intake of macro- and micronutrients, reducing indigestion, the degree of malabsorption, and other risk factors in order to prevent or treat malnutrition associated with exocrine pancreatic insufficiency. Nutritional status and nutritional interventions depend on this. Attention is drawn to the indication of different nutritional options depending on the severity of the course of exocrine insufficiency and the presence of diabetes (10–15% need oral nutritional supplements, 5% — enteral nutrition through a tube, and about 1% — parenteral nutrition). The European Society for Clinical Nutrition and Metabolism (ESPEN) Guidelines for Nutritional Screening are presented. The question of the impact of chronic pancreatitis and exocrine pancreatic insufficiency on digestion with the development of maldigestion and malabsorption and the importance of these factors for the quality of life is discussed. The author reviewed in detail the metabolism of carbohydrates, proteins, and fats in enzyme pancreatic insufficiency and the importance of this knowledge in providing nutritional recommendations. The digestion of lipids in the lumen of the small intestine depends on pancreatic lipase and cofactors such as colipase and bile acids. Lipases of the stomach and salivary glands play a minor role in the digestion of triglycerides and cannot compensate for the insufficient fat digestion. There are no enzyme systems for digesting triglycerides in the brush border membrane. Therefore, lipid digestion is reduced due to insufficient secretion of lipase and a decrease in the concentration of bile acids in the lumen. Attention is paid to research methods that determine the state of fat, lean mass, muscle state, bone health, and resting energy expenditure, provide an opportunity to conduct a detailed assessment of current and usual food consumption, which promotes successful treatment.

Single particle investigation of triolein digestion using optical manipulation, polarized video microscopy, and SAXS

Hypothesis: Understanding how soft colloids, such as food emulsion droplets, transform based on their environment is critical for various applications, including drug and nutrient delivery and biotechnology. However, the mechanisms behind colloidal transformations within individual oil droplets still need to be better understood.Experiments: This study employs optical micromanipulation with microfluidics and polarized optical video microscopy to investigate the pancreatic lipase- and pH-triggered colloidal transformations in a single triolein droplet. Small-angle X-ray scattering (SAXS) provides complementary statistical insights and allows for detailed structural assignment.Findings: Optical video microscopy recorded the transformation of individual triolein emulsion droplets, with the smooth surface of these spherical particles becoming rough and the entire volume eventually being affected. The polarized microscopy revealed the coexistence of at least two distinct structures in a single particle during digestion, with their ratio and distribution altered by pH. The SAXS analysis assigned the optical anisotropy to emulsified inverse hexagonal- and multilamellar phases, coexisting with isotropic structures such as the micellar cubic phase. These results can help understand the phase transformations inside an emulsion droplet during triglyceride digestion and guide the design of advanced food emulsions.

Appraisal of Pancreatic Lipase Inhibitory Potential of Ziziphus oenoplia (L.)Mill. Leaves by In Vitro and In Silico Approaches.

Pancreatic lipase is one of the crucial lipolytic enzymes of the gut that actively facilitates the digestion and absorption of the dietary triglycerides and cholesteryl esters. Although it has been deemed as one of the most reliable targets for the treatment of obesity and/or dyslipidemia, to date, orlistat is the only known FDA-approved, effective, oral pancreatic lipase inhibitor available for clinical use apart from the centrally acting antiobesity agents. However, it is known to be associated with adverse gastrointestinal and renal complications. In this study, we attempted to assess the antioxidant and porcine pancreatic lipase inhibitory potentials of Ziziphus oenoplia (L.)Mill. leaves through a systematic combination of in vitro and in silico approaches. Among the four different extracts including petroleum ether extract, ethyl acetate extract, ethanolic extract, and aqueous extract obtained through successive solvent extraction, the ethyl acetate extract has outperformed the other extracts and orderly displayed competent peroxide scavenging (IC50 value: 267.30 μg/mL) and porcine pancreatic lipase inhibitory (IC50 value: 444.44 μg/mL) potentials compared to the selected reference compounds: ascorbic acid (IC50 value: 251.50 μg/mL) and orlistat (IC50 value: 502.51 μg/mL) in the selected in vitro assay models. In addition, based on the molecular docking simulations of the six essential phytoconstituents of the leaves of Ziziphus oenoplia (L.)Mill. and their respective chemical analogues against the crystal structure of pancreatic lipase-colipase complex (PDB ID: 1LPB), four best-ranked molecules (PubChem CIDs: 15515703, 132582306, 11260294, and 44440845) have been proposed. Further, among these, the interaction potentials of the two top-ranked molecules (PubChem CIDs: 132582306 and 15515703) were analyzed through molecular dynamics (MD) simulations at a trajectory of 100 ns. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were theoretically predicted for all of the molecules using Swiss ADME and ADMET lab2.0. In conclusion, Ziziphus oenoplia (L.)Mill. leaves could become a prominent source for various potent bioactive compounds that may serve as prospective leads for the development of clinically cognizable pancreatic lipase inhibitors, provided their pharmacokinetic and in particular toxicity properties are thoroughly optimized.

Cellulose Nanofiber Platform for Pesticide Sequestration in the Gastrointestinal Tract.

Exploitation of nature-derived materials is an important approach to promote environmental sustainability. Among these materials, cellulose is of particular interest due to its abundance and relative ease of access. As a food ingredient, cellulose nanofibers (CNFs) have found interesting applications as emulsifiers and modulators of lipid digestion and absorption. In this report, we show that CNFs can also be modified to modulate the bioavailability of toxins, such as pesticides, in the gastrointestinal tract (GIT) by forming inclusion complexes and promoting interaction with surface hydroxyl groups. CNFs were successfully functionalized with (2-hydroxypropyl)-β-cyclodextrin (HPBCD) using citric acid as a crosslinker via esterification. Functionally, the potential for pristine and functionalized CNFs (FCNFs) to interact with a model pesticide, boscalid, was tested. Based on direct interaction studies, adsorption of boscalid saturated at around 3.09% on CNFs and at 12.62% on FCNFs. Using an in vitro GIT simulation platform, the adsorption of boscalid on CNFs/FCNFs was also studied. The presence of a high-fat food model was found to have a positive effect in binding boscalid in a simulated intestinal fluid environment. In addition, FCNFs were found to have a greater effect in retarding triglyceride digestion than CNFs (61% vs 30.6%). Overall, FCNFs were demonstrated to evoke synergistic effects of reducing fat absorption and pesticide bioavailability through inclusion complex formation and the additional binding of the pesticide onto surface hydroxyl groups on HPBCD. By adopting food-compatible materials and processes for production, FCNFs have the potential to be developed into a functional food ingredient for modulating food digestion and the uptake of toxins.

Lactobacillus casei-derived postbiotics inhibited digestion of triglycerides, glycerol phospholipids and sterol lipids via allosteric regulation of BSSL, PTL and PLA2 to prevent obesity: perspectives on deep learning integrated multi-omics.

The anti-obesity potential of probiotics has been widely reported, however their utilization in high-risk patients and potential adverse reactions have led researchers to focus their attention on postbiotics. Herein, pseudo-targeted lipidomics linked with deep learning-based metabolomics was utilized to dynamically characterize the postbiotic potential of heat-inactivated Lactobacillus casei JCM1134 supplementation after a high-fat diet in treating obesity. MG (ranged from 423.0 ± 1.4 mg L-1 to 331.45 ± 2.3 mg L-1), LPC (ranged from 13.1 ± 0.08 mg L-1 to 10.2 ± 0.1 mg L-1) and Cho (ranged from 9.0 ± 0.3 mg L-1 to 5.7 ± 0.2 mg L-1) in intestinal digestive products were significantly decreased, indicating that the digestion of lipid was inhibited. 8-C-glucosylorobol, from Lactobacillus casei, was confirmed from quantitative results and molecular simulation calculations to inhibit the transformation of TG, DG, and ChE through weakening hydrogen bonds between enzymes and substrates and reducing the binding energy. Pristimerin and 2,4-quinolinediol can effectively reduce the hydrogen bonding force between PC and phospholipase A2, which were related to the obstruction of phosphatidylcholine digestion. This research deepened the understanding of the mechanism underlying the inactivated probiotics affecting lipid digestion, establishing the critical groundwork for clinical application of probiotics in inhibiting obesity.

Coconut oil as a therapeutic treatment for alzheimer's disease: a review

The coconut tree ( Cocos nucifera ) which is also known as the “Tree of life” has its own values in each part of the tree and coconut oil is more prestigious among them. At present, the consumption of coconut oil is booming all around the world owing to its tremendous health benefits. The unique chemical composition of coconut oil enriched with medium chain fatty acids (MCFAs) has led to the exploration of these nutritional and therapeutic influences. Unlike the long chain fatty acids (LCFAs), the MCFAs generated from the digestion of medium chain triglycerides (MCTs) has a specific pathway for the metabolism, as it bypasses the lymphatic system and enter the liver directly through the portal vein. Due to such distinct attributes in absorption and metabolism, MCTs are readily capable of forming ketone bodies than other triglycerides. These ketone bodies are a competent energy source for the brains, especially those having cognitive impairments like Alzheimer's disease (AD). AD is a neurodegenerative disease characterized clinically by accelerating shortfalls in memory and behavioral changes. The principal biochemical hallmarks behind the pathogenesis of AD are the development of extracellular amyloid β plaques and the accumulation of intracellular neurofibrillary tangles. Occurrence of Cardiovascular diseases (CVD) with elevated LDL levels, hypertension, Type 2 diabetes, obesity, and insulin resistance are some key risk factors that are responsible for the increasing prevalence and incidence of AD. There is sufficient evidence to prove that MCTs in coconut oil are metabolized and absorbed in such a way that retards the severity of these physiological risk factors. Besides, coconut oil is endowed with many polyphenolic compounds that are serving as antioxidants by combating oxidative stress and inflammation, which in turn downregulates the etiology of AD. But depending on the different processing conditions applied in extraction techniques of coconut oil, variations in antioxidant capacity can take place. Even though there are inadequacies in peer-reviewed large cohort clinical data for the long run, this article reviews that coconut oil, its constituents, and metabolism have positive findings on the potentiality to treat AD as a nutritional supplement.

Molecular dynamics revealed the effect of epoxy group on triglyceride digestion

The digestion behavior of epoxy triglyceride, the main cytotoxic product of deep-frying oil, remains unknown, which may affect its biosafety. In this study, epoxy triglyceride (EGT) and triglyceride (GT) were used to reveal the effect of epoxy group on digestion. Digestibility rate analysis showed that the free fatty acids release rate of EGT was slower. To clarify this phenomenon, binding ability with salt ions in digestive juice and particle size were also been studied. Cluster size analysis indicated that epoxy group increased triglyceride particle size, resulting in smaller contact area between EGT and lipase. Interface behaviors displayed EGT decreased binding ability with salt ions in digestive juice. Spectroscopic analysis showed EGT caused the red shift of lipase peak, indicating that epoxy group changed lipase structure. Molecular dynamics simulation suggested EGT leads to loosen lipase structure. In conclusion, this study highlights that epoxy group could weaken the triglyceride digestion.

Identification of novel potent pancreatic lipase inhibitors from Ficus racemosa

Introduction and Aim: Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It is considered to be main reason for a number of physiological changes that resulting in many metabolic disorders such as cardiovascular diseases, diabetes, musculoskeletal disorders and various cancer types. Obesity develops from long-termed physiological imbalances in energy expenditure.. One of the therapeutic strategies in managing obesity is inhibition of pancreatic lipase, a key enzyme responsible for the digestion of fats and triglycerides. The aim of the present study was to synthesize silver nanoparticles (Ag-NP) from Ficus racemosa fruit extract and to analyze its activity on pancreatic lipase enzyme using spectroscopic, in vitro and in silico methods.&#x0D; Materials and Methods: The phytoconstituent were separated in Ficus racemosa fruit extract by thin layer chromatography technique. The bioactive compound was also identified by gas chromatography-mass spectrometry analysis. Pancreatic lipase inhibition assay was performed in vitro and confirmed by molecular docking analysis. &#x0D; Results: The F. racemosa fruit showed the highest pancreatic lipase inhibitory activity. Molecular docking studies also exhibited good binding affinity of compounds (Diethyl Phthalate) with pancreatic lipase enzymes. &#x0D; Conclusion: Finally, it is concluded that further derivation of such compounds could serve as the new templates for obesity.

Bovine Milk-Derived Emulsifiers Increase Triglyceride Absorption in Newborn Formula-Fed Pigs.

Efficient lipid digestion in formula-fed infants is required to ensure the availability of fatty acids for normal organ development. Previous studies suggest that the efficiency of lipid digestion may depend on whether lipids are emulsified with soy lecithin or fractions derived from bovine milk. This study, therefore, aimed to determine whether emulsification with bovine milk-derived emulsifiers or soy lecithin (SL) influenced lipid digestion in vitro and in vivo. Lipid digestibility was determined in vitro in oil-in-water emulsions using four different milk-derived emulsifiers or SL, and the ultrastructural appearance of the emulsions was assessed using electron microscopy. Subsequently, selected emulsions were added to a base diet and fed to preterm neonatal piglets. Initially, preterm pigs equipped with an ileostomy were fed experimental formulas for seven days and stoma output was collected quantitatively. Next, lipid absorption kinetics was studied in preterm pigs given pure emulsions. Finally, complete formulas with different emulsions were fed for four days, and the post-bolus plasma triglyceride level was determined. Milk-derived emulsifiers (containing protein and phospholipids from milk fat globule membranes and extracellular vesicles) showed increased effects on fat digestion compared to SL in an in vitro digestion model. Further, milk-derived emulsifiers significantly increased the digestion of triglyceride in the preterm piglet model compared with SL. Ultra-structural images indicated a more regular and smooth surface of fat droplets emulsified with milk-derived emulsifiers relative to SL. We conclude that, relative to SL, milk-derived emulsifiers lead to a different surface ultrastructure on the lipid droplets, and increase lipid digestion.

The impact of emulsion droplet size on in vitro lipolysis rate and in vivo plasma uptake kinetics of triglycerides and vitamin D3 in rats.

Emulsions play an important role in the process of triglyceride (TG) digestion (lipolysis). Through emulsification, the oil-water interface is increased by orders of magnitude. This often leads to faster and more efficient lipolysis, which is potentially beneficial for the intestinal uptake of oils and lipophilic compounds. In this paper, we first examined the effect of emulsion droplet size on the in vitro lipolysis rate. Then an in vivo experiment was performed, to examine the plasma uptake kinetics of TGs and vitamin D3 (vitD3) over a 24 hours period after oral administration of the emulsions in rats. Basic corn oil emulsions loaded with vitD3 were prepared using polysorbate 80 as the emulsifier, with three different droplet sizes (D[3,2]): ∼3 μm (large), ∼1 μm (medium) and ∼0.3 μm (small). In vitro lipolysis experiments showed, as expected, that smaller droplets were lipolyzed more rapidly. However, the medium emulsion had by far the highest rate of lipolysis per surface area. This was attributed to bile salt limitation, polysorbate 80 lipolysis inhibition and TG digestion product accumulation. In vivo, the two smallest emulsions showed the highest uptake (Cmax and AUC) of vitD3 and TG, while the largest emulsion and bulk oil control showed lower values. However, only the (incremental) TG plasma values and kinetics displayed some statistically significant differences. These findings may have relevance for the formulation of functional foods/beverages or delivery units containing oils or lipophilic bioactives.

Hydrolysis of Triglycerides in Cream Using Porcine Pancreatic Lipase

The development of an enzyme-mediated reaction for the first-year general, organic, and biological chemistry (GOB) teaching laboratory is of significant importance so that the factors that affect enzyme-mediated reactions can be adequately demonstrated, reinforcing the lecture portion of the GOB course. Some of the factors that affect these types of reactions include, but are not limited to, enzyme concentration, substrate concentration, and temperature. The experiment reported herein utilizes porcine pancreatic lipase (PPL) to catalyze the hydrolysis of triglycerides within cream. The amount of time required to afford triglyceride hydrolysis was probed by altering the concentration of PPL and the temperature at which the reaction was performed. In addition, to provide the students with a hands-on demonstration of how bile salts aid in the digestion of triglycerides, various trials were performed to explore the effect of altering bile salt concentration. Finally, the data obtained from the enzyme concentration trials, the temperature trials, and the bile salt concentration trials were graphed to provide a visual representation of how triglyceride hydrolysis, mediated by PPL, is affected by these various factors.

Impact of Ferroquine on the Solubilization of Artefenomel (OZ439) during in Vitro Lipolysis in Milk and Implications for Oral Combination Therapy for Malaria.

Milk is an attractive lipid-based formulation for the delivery of poorly water-soluble drugs to pediatric populations. We recently observed that solubilization of artefenomel (OZ439) during in vitro intestinal lipolysis was driven by digestion of triglycerides in full-cream bovine milk, reflecting the ability of milk to act as an enabling formulation in the clinic. However, when OZ439 was co-administered with a second antimalarial drug, ferroquine (FQ) the exposure of OZ439 was reduced. The current study therefore aimed to understand the impact of the presence of FQ on the solubilization of OZ439 in milk during in vitro intestinal digestion. Synchrotron small-angle X-ray scattering was used for in situ monitoring of drug solubilization (inferred via decreases in the intensity of drug diffraction peaks) and polymorphic transformations that occurred during the course of digestion. Quantification of the amount of each drug solubilized over time and analysis of their distributions across the separated phases of digested milk were determined using high-performance liquid chromatography. The results show that FQ reduced the solubilization of OZ439 during milk digestion, which may be due to competitive binding of FQ to the digested milk products. Interactions between the protonated FQ-H+ and ionized liberated free fatty acids resulted in the formation of amorphous salts, which removes the low-energy crystalline state as a barrier to dissolution of FQ, while inhibiting the solubilization of OZ439. We conclude that although milk could enhance the solubilization of poorly water-soluble OZ439 during in vitro digestion principally due to the formation of fatty acids, the solubilization efficiency was reduced by the presence of FQ by competition for the available fatty acids. Assessment of the solubilization of both drugs during digestion of fixed-dose combination lipid formulations (such as milk) is important and may rationalize changes in bioavailability when compared to that of the individual drugs in the same formulation.