Tripalmitin

Comparing cefotaxime and ceftriaxone in combating meningitis through nose-to-brain delivery using bio/chemoinformatics tools.[Pubmed:33277611]

Sci Rep. 2020 Dec 4;10(1):21250.

Bio/chemoinformatics tools can be deployed to compare antimicrobial agents aiming to select an efficient nose-to-brain formulation targeting the meningitis disease by utilizing the differences in the main structural, topological and electronic descriptors of the drugs. Cefotaxime and ceftriaxone were compared at the formulation level (by comparing the loading in gelatin and Tripalmitin matrices as bases for the formation of nanoparticulate systems), at the biopharmaceutical level (through the interaction with mucin and the P-gp efflux pumps) and at the therapeutic level (through studying the interaction with S. pneumoniae bacterial receptors). GROMACS v4.6.5 software package was used to carry-out all-atom molecular dynamics simulations. Higher affinity of ceftriaxone was observed compared to cefotaxime on the investigated biopharmaceutical and therapeutic macromolecules. Both drugs showed successful docking on mucin, P-gp efflux pump and S. pneumoniae PBP1a and 2b; but ceftriaxone showed higher affinity to the P-gp efflux pump proteins and higher docking on mucin. Ceftriaxone showed less out-of-matrix diffusion and higher entrapment on the gelatin and the Tripalmitin matrices. Accordingly, Ceftriaxone gelatin nanospheres or Tripalmitin solid lipid nanoparticles may pose a more feasible and efficient nose-to-brain formulation targeting the meningitis disease compared to the cefotaxime counterparts.

Solvent-free enzymatic synthesis of 1,2-dipalmitoylgalloylglycerol: Characterization and optimization of reaction condition.[Pubmed:33243556]

Food Chem. 2020 Nov 17:128604.

A novel diacylglycerol-based galloyl structured lipid, 1,2-dipalmitoylgalloylglycerol (DPGG), was synthesized using the enzymatic transesterification of propyl gallate (PG) and Tripalmitin under solvent-free condition. An immobilized and commercially available food-grade Candida antarctica lipase B, Lipozyme(R) 435, was used as the biocatalyst. The reaction variables that affect the yield of DPGG were optimized using a 3(3) full factorial design. At 70 degrees C, DPGG was obtained at a yield of 33.0 +/- 2.0% with PG conversion at 44.8 +/- 1.8% when the following condition was used: 25 substrate molar ratio of Tripalmitin to PG, 120 h reaction time, and 25% enzyme load relative to the total substrate weight. The structure of reaction product was elucidated using Fourier-transform infrared spectroscopy (FT-IR), electrospray ionization high-resolution accurate-mass tandem mass spectrometry (ESI-HRAM-MS/MS), and 1D and 2D nuclear magnetic resonance spectroscopy (NMR). The effects of different lipases and galloyl donors/acceptors on the transesterification were also investigated.

Multiple beta Forms of Saturated Monoacid Triacylglycerol Crystals.[Pubmed:33147818]

Molecules. 2020 Nov 2;25(21). pii: molecules25215086.

We have investigated the polymorphism of triacylglycerol (TAG) crystals as they affect the qualities such as shelf life, mouth feel, and texture of chocolate and other products. Saturated monoacid TAGs, like trilaurin, are considered as models for TAG crystallization; however, there is still debate about the number of their polymorphs that exist. In this study, we characterized a set of novel polymorphs, beta forms of saturated monoacid TAGs, which were obtained via different pathways depending on the crystallization history, by polarized light microscopy, X-ray diffraction, and differential scanning calorimetry. Saturated monoacid TAGs were crystallized as the unstable polymorphs, the alpha or beta' forms first, and then they were transformed into beta forms by solid-solid transformations. The beta form that had transformed from beta' changed its morphology by a polymorphic transformation, while the beta form made from the alpha form kept its spherulite morphology. The beta forms obtained showed different melting points. Additional heat treatment promoted further polymorphic transformation. Four novel beta forms were found for each of the saturated monoacid TAGs, trilaurin, trimyristin, Tripalmitin, and tristearin. They showed similar polymorphism with the same subcell packing.

Filgrastim loading in PLGA and SLN nanoparticulate system: a bioinformatics approach.[Pubmed:32643442]

Drug Dev Ind Pharm. 2020 Aug;46(8):1354-1361.

OBJECTIVE: In this research work, we hypothesized to predict the nanoparticulate system, best suited for targeted delivery of filgrastim. Significance: Targeted delivery of filgrastim to bone marrow is required to decrease the incidence of neutropenia/febrile neutropenia. This is achieved by nanoparticulate systems, duly designed by bioinformatics approach. METHOD: The targeted delivery of filgrastim in nanoparticulate system was achieved by molecular dynamics (MD) simulation studies. Two matrices comprising PLGA and SLN (Tripalmitin, core component of SLN system) were modeled separately with proposed drug filgrastim. Energy minimization of all systems was done using the steepest descent method. PLGA and Tripalmitin systems were equalized at 310 degrees C, at 1 bar pressure with Berendsen barostat for 200 ps using a v-rescale thermostat for 100 ps. Atomistic MD simulations of four model system and mass density of interacting systems were calculated. RESULTS: The mass density maps of each nanoparticle system, that is, PLGA and Tripalmitin showed an increase in density toward the end of the simulation. The contact numbers attained equilibria with the average number of approx.. 1500 contacts in case of Tripalmitin-filgrastim system. While PLGA-filgrastim system shows lesser contacts as compared to Tripalmitin with average contacts of approx. 1000.The binding free energy was predicted to be -1104 kJ/mol in Tripalmitin-filgrastim complex and -421 kJ/mol in PLGA-filgrastim system. CONCLUSION: Findings of study revealed that both nanoparticle systems assumed to be good model for drug-carrier systems. Though SLN systems were thought to be more appropriate than PLGA, still the in vivo findings could ascertain this hypothesis in futuristic work.

Biochemical Characterization of a Lipolytic Enzyme From Aspergillus oryzae That Hydrolyzes Triacylglycerol and Sterol Esters.[Pubmed:32617843]

Appl Biochem Biotechnol. 2020 Nov;192(3):910-922.

A novel lipolytic enzyme-encoding gene, lipO745, from Aspergillus oryzae RIB40 was cloned and expressed in Pichia pastoris. Purified recombinant LipO745 (rLipO745) had a molecular mass of approximately 60 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. rLipO745 exhibited maximum activity at 40 degrees C and pH 7.0 and was stable at temperatures Tripalmitin, and triolein, indicating lipase activity, and toward cholesteryl acetate, butyrate, palmitate, and oleate, indicating sterol esterase activity. Transesterification activities between tributyrin and cholesterol or between tributyrin and campesterol were also determined.

Crystallization-Induced Network Formation of Tri- and Monopalmitin at the Middle-Chain Triglyceride Oil/Air Interface.[Pubmed:32520568]

Langmuir. 2020 Jul 7;36(26):7566-7572.

Crystalline glycerides play an important role in the formation of multiphase systems such as emulsions and foams. The stabilization of oil/water interfaces by glyceride crystals has been extensively studied compared to only few studies which have been dedicated to oil/air interfaces. This study investigates the crystallization and network formation of Tripalmitin (TP) and monopalmitin (MP) at the middle-chain triglyceride (MCT) oil/air interface. TP crystals were found to crystallize in the bulk before aggregating as large rectangular crystal conglomerates at the MCT oil/air interface. This leads to the slow formation of a plastic deformable, macroscopic crystal layer with high interfacial rheological moduli. MP crystals form directly at the MCT oil/air interface resulting in a comparatively fast formation of an elastic deformable network. Crystals with tentacle-like morphology were found to be responsible for the network elasticity. In this work, we show how interfacial crystallization dynamics and mechanical strength can be linked to the molecular structure and crystallization behavior of glyceride crystals.

Hot Melt Coating of Amorphous Carvedilol.[Pubmed:32517255]

Pharmaceutics. 2020 Jun 6;12(6). pii: pharmaceutics12060519.

The use of amorphous drug delivery systems is an attractive approach to improve the bioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility. However, the pharmaceutical performance of many neat amorphous drugs is compromised by their tendency for recrystallization during storage and lumping upon dissolution, which may be improved by the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a solvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with Tripalmitin containing 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated amorphous particles were assessed in terms of their physical stability during storage and their drug release during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to be mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20% (w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core, however, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the interface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated the feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from amorphous systems but at the same time highlights the importance of surface-mediated processes for the physical stability of the amorphous form.

Moisturizing effects of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using deionized and magnetized water by in vivo and in vitro methods.[Pubmed:32440320]

Iran J Basic Med Sci. 2020 Mar;23(3):337-343.

Objectives: The present study aimed to determine and compare moisturizing and occlusion effects of different solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using magnetized water and deionized water. Materials and Methods: SLN formulations were prepared using various lipids, including Tripalmitin, Compritol(R), Precirol(R), and emulsifiers including Poloxamer and Tween 80. NLC formulations were also prepared with oleic acid and the same solid lipids. Two types of formulations were prepared; first with deionized water and then with magnetized water. Formulations were prepared using high shear homogenization and ultrasound methods. The products were analyzed by PSA (particle size analyzer), DSC (differential scanning calorimetry), and TEM (transmission electron microscopy). The moisturizing effect of formulations was determined by in vivo and in vitro methods. Results: Findings of the assessments demonstrated that in products prepared with magnetized water, 5% SLN Precirol(R) had the most moisturizing effect in vivo and 5% SLN Compritol(R) had the most moisturizing effect in vitro. The use of magnetized water in formulations can improve the effectiveness and increase the stability of moisturizing products. Conclusion: In this study, all products prepared with magnetized water showed more stability, smaller size, and more moisturizing effects compared with products prepared with deionized water.

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model.[Pubmed:32117930]

Front Bioeng Biotechnol. 2020 Feb 11;8:50.

Combination chemotherapy, administrating two chemotherapeutic agents concurrently, comes into prominence, as the heterogeneity or the level of the disease necessitates a collaborative action. Curcumin, isolated from turmeric, and piperine, isolated from black long pepper, are two dietary polyphenols studied for their intrinsic anti-cancer properties against various cancer types including colorectal cancer (CRC). Furthermore, piperine improves the therapeutic effect of curcumin. Addressing this mutual behavior, this study combines curcumin and piperine within emulsome nanoformulations. Curcumin- (CurcuEmulsomes) and piperine-loaded emulsomes (PiperineEmulsomes) have established a uniform, stable, spherical dispersion with average diameters of 184.21 and 248.76 nm, respectively. The solid Tripalmitin inner core achieved encapsulation capacities of up to 0.10 mg/ml curcumin and 0.09 mg/ml piperine content. While piperine treatment alone - in its both free and emulsome forms - showed no inhibition in the proliferation of HCT116 cells in vitro, its presence as the second drug agent enhanced curcumin's effect. Combination of 7 muM PiperineEmulsome and 25 muM CurcuEmulsome concentrations was found to be most effective with an inhibition of cell proliferation of about 50% viability. Cell cycle arrest at G2/M phase and induced apoptosis verified the improved anti-cancer characteristics of the therapy. While CurcuEmulsomes achieved a fourfold increase in Caspase 3 level, combination of treatment with PiperineEulsomes achieved a sixfold increase in the level of this apoptotic marker. Combinational treatment of HCT116 cells with CurcuEmulsomes and PiperineEmulsomes improved the anticancer activity of the compounds and highlighted the potential of the approach for further in vivo studies.

Development of Lipid-Based Nanocarriers for Increasing Gastrointestinal Absorption of Lupinifolin.[Pubmed:32005042]

Planta Med. 2020 Mar;86(5):364-372.

Lupinifolin, a plant flavonoid, has been reported to possess various pharmacological effects. It most likely exerts low oral bioavailability because of poor water solubility. The objective of this study was to develop lipid nanocarriers as drug delivery systems to increase the gastrointestinal absorption of lupinifolin extracted from Albizia myriophylla. Three types of nanocarriers, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were prepared by an emulsification-sonication technique. All three types of nanocarriers loaded with lupinifolin, lupinifolin-loaded solid lipid nanoparticles, lupinifolin-loaded nanostructured lipid carriers, and lupinifolin-loaded nanoemulsions, were successfully synthesized. The lipid components chosen to formulate nanocarriers were Tripalmitin and/or medium chain triglyceride. Physicochemical characterizations along with releasing profiles of lupinifolin-loaded lipid nanocarriers were compared. It was found that the best lipid nanocarrier for lupinifolin was lupinifolin-loaded nanostructured lipid carriers, which demonstrated the particle size of 151.5 +/- 0.1 nm, monodispersity distribution with a polydispersity index of 0.24, negative surface charge at - 41.2 +/- 0.7 mV, high encapsulation (99.3%), and high loading capacity (5.0%). The obtained lupinifolin-loaded nanostructured lipid carriers exhibited prolonged release in a simulated circulatory system but produced a low release in gastrointestinal conditions (3.7%). Intestinal permeability of the nanocarriers was further evaluated in everted intestinal sacs. The results from the ex vivo study indicated that lupinifolin-loaded nanostructured lipid carriers significantly increased the absorption of lupinifolin compared to the native form. In conclusion, lupinifolin-loaded lipid nanocarriers were successfully formulated as delivery systems to enhance its oral bioavailability. Further in vivo experiments are needed to validate the results from this study.

A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes.[Pubmed:31873788]

Diabetologia. 2020 Mar;63(3):611-623.

AIMS/HYPOTHESIS: Prediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes. METHODS: We evaluated the effect of a single bout of whole-body resistance exercise (seven exercises, three sets, 10-12 repetitions at 80% of one-repetition maximum) on postprandial lipid metabolism in ten middle-aged (50 +/- 9 years), overweight/obese (BMI: 33 +/- 3 kg/m(2)), sedentary men with prediabetes (HbA1c >38 but <48 mmol/mol [>5.7% but <6.5%]), or fasting plasma glucose >5.6 mmol/l but <7.0 mmol/l or 2 h OGTT glucose >7.8 mmol/l but <11.1 mmol/l). We used a randomised, crossover design with a triple-tracer mixed meal test (ingested [((13)C4)3]Tripalmitin, i.v. [U-(13)C16]palmitate and [(2)H5]glycerol) to evaluate chylomicron-TG and total triacylglycerol-rich lipoprotein (TRL)-TG kinetics. We used adipose tissue and skeletal muscle biopsies to evaluate the expression of genes regulating lipolysis and lipid oxidation, skeletal muscle respirometry to evaluate oxidative capacity, and indirect calorimetry to assess whole-body lipid oxidation. RESULTS: The single bout of resistance exercise reduced the lipaemic response to a mixed meal in obese men with prediabetes without changing chylomicron-TG or TRL-TG fractional clearance rates. However, resistance exercise reduced endogenous and meal-derived fatty acid incorporation into chylomicron-TG and TRL-TG. Resistance exercise also increased whole-body lipid oxidation, skeletal muscle mitochondrial respiration, oxidative gene expression in skeletal muscle, and the expression of key lipolysis genes in adipose tissue. CONCLUSIONS/INTERPRETATION: A single bout of resistance exercise improves postprandial lipid metabolism in obese men with prediabetes, which may mitigate the risk for cardiovascular disease and type 2 diabetes.

Construction of a Hydrogel Pectin-Based Triglyceride Optical Biosensor with Immobilized Lipase Enzymes.[Pubmed:31766218]

Biosensors (Basel). 2019 Nov 13;9(4). pii: bios9040135.

A novel and simple optical biosensor to detect triglycerides (TGs) has been successfully constructed by using pectin hydrogel membrane as the indicator pH and chromoionophore ETH 5294 (CI), with lipase as the catalyst. The enzymatic working system against TGs releasing H(+) ions will affect the color absorbance of CI. The characterization results show that a TG biosensor has the optimum condition and sensitivity at the phosphate buffer concentration of 50 mM, pH 7, and enzyme loading of 60 mug. The biosensor works at the Tripalmitin (TP) concentration range of 100-400 mg/dL. With the sensitivity of 0.001 (A/(mg/dL)), the biosensor response reaches stability after five minutes, and the limit of detection (LOD) of the TG optical biosensor is 15 mg/dL. Relative standard deviation (RSD) in a reproducibility test was 2.5%, with a 15-day lifespan.

Internal Structure of Nanometer-Sized Droplets Prepared by Antisolvent Precipitation.[Pubmed:31547660]

Langmuir. 2019 Oct 22;35(42):13578-13587.

Antisolvent precipitation (AP) is a low-cost and less-invasive preparation alternative for organic nanoparticles compared to top-down methods such as high-pressure homogenization or milling. Here we report on particularly small organic nanoparticles (NPs) prepared by AP. It has been found for various materials that these NPs in their liquid state exhibit a significant degree of molecular order at their interface toward the dispersion medium including ubiquinones (coenzyme Q10), triglycerides (trimyristin, Tripalmitin), and alkanes (tetracosane). This finding is independent of the use of a stabilizer in the formulation. While this is obviously a quite general interfacial structuring effect, the respective structural details of specific NPs systems might differ. Here, a detailed structural characterization of very small liquid coenzyme Q10 (Q10) NPs is presented as a particular example for this phenomenon. The Q10 NPs have been prepared by AP in the presence of two different stabilizers, sodium dodecyl sulfate (SDS) and pentaethylene glycol monododecyl ether (C12E5), respectively, and without any stabilizer. The NPs' size is initially analyzed by photon correlation spectroscopy (PCS). The SDS-stabilized Q10 NPs have been studied further by differential scanning calorimetry (DSC), small-angle X-ray and neutron scattering (SAXS, SANS), wide-angle X-ray scattering (WAXS), and cryogenic transmission electron microscopy (CryoTEM). A simultaneous analysis of SAXS and contrast variation SANS studies revealed the molecular arrangement within the interface between the NPs and the dispersion medium. The Q10 NPs stabilized by SDS and C12E5, respectively, are small (down to 19.9 nm) and stable (for at least 16 months) even when no stabilizer is used. The SDS-stabilized Q10 NPs reported here, are therewith, to the best of our knowledge, the smallest organic NPs which have been reported to be prepared by AP so far. In particular, these NPs exhibit a core-shell structure consisting of an amorphous Q10 core and a surrounding shell, which is mainly composed of oriented Q10 molecules and aligned SDS molecules. This structure suggests a significant amphiphilic behavior and a rather unexpected stabilizing role of Q10 molecules.

On the Structure of Solid Lipid Nanoparticles.[Pubmed:31532892]

Small. 2019 Nov;15(45):e1903156.

Solid lipid nanoparticles (SLNs) have a crystalline lipid core which is stabilized by interfacial surfactants. SLNs are considered favorable candidates for drug delivery vehicles since their ability to store and release organic molecules can be tailored through the identity of the lipids and surfactants used. When stored, polymorphic transitions in the core of drug-loaded SLNs lead to the premature release of drug molecules. Significant experimental studies have been conducted with the aim of investigating the physicochemical properties of SLNs, however, no molecular scale investigations have been reported on the behaviors that drive SLN formation and their polymorphic transitions. A combination of small angle neutron scattering and all-atom molecular dynamics simulations is therefore used to yield a detailed atomistic description of the internal structure of an SLN comprising triglyceride, Tripalmitin, and the nonionic surfactant, Brij O10 (C18:1 E10 ). The molecular scale mechanisms by which the surfactants stabilize the crystalline structure of the SLN lipid core are uncovered. By comparing these results to simulated liquid and solid aggregates of Tripalmitin lipids, how the morphology of the lipids vary between these systems is demonstrated providing further insight into the mechanisms that control drug encapsulation and release from SLNs.

Solvent-Free Alcoholysis of Tripalmitin to Produce 2-Monoglyceride as Precursor for 1, 3-Oleoyl-2-Palmitoylglycerol.[Pubmed:31506906]

Appl Biochem Biotechnol. 2020 Mar;190(3):867-879.

2-monoglyceride (2-MAG) was essential to produce high purity of 1, 3-Oleoyl-2-palmitoylglycerol (OPO), an important infant formula additive. Traditional synthesis of 2-MAG requires chemical solvent to solve the high melting point substrate, yielding the risk of solvent residue in OPO. This paper developed a solvent-free synthesis route of 2-MAG by alcoholysis of high melting point Tripalmitin (PPP). Ethyl palmitate (EP), one of the reaction byproducts, was added in the beginning of alcoholysis process to promote the solubleness of high melting point PPP, avoiding the addition of toxic chemical solvent. The product of alcoholysis was separated by two-step molecular distillations. Separated DAG was used to produce 2-MAG and the final conversion of 2-MAG reached about 85.90%, with the purity of 92.36%. 2-MAG was trans-esterified to OPO with ethyl oleate, and the yield of OPO was up to 85.06% with 80.17% palmitic acid located on sn-2 position. The solvent-free synthesis route avoids the usage of hazardous chemical solvents, providing safer infant formula additive.