Tripalmitin Research Articles

Optimization and characterization of quercetin-loaded solid lipid nanoparticles for biomedical application in colorectal cancer

BackgroundColorectal cancer (CRC) is a type of cancer that affects the colon or rectum and occurs in individuals over the age of 50, although it can affect people of all ages. Quercetin is a flavonoid, which is a type of plant pigment with antioxidant and anti-inflammatory properties. Some studies have explored the potential of quercetin as an adjuvant therapy to enhance the effectiveness of chemotherapy or radiation therapy.MethodologyIn the proposed work, the nano-biomaterials of solid lipids such as stearic acid (SA) and tripalmitin (TpN) as well as the surfactants tween 80 and span 80 were used to prepare novel quercetin (QuR)-loaded-solid lipid nanoparticles (QuR-SLNs) for medical applications in colorectal cancer (CRC). The resulting bio-nano SLNs’ mean entrapment efficiency (EE) and particle size (PS) were optimized by Box–Behnken design (BBD) approach based on the response-like surface methodology (RSM). The variables include lipid ratio (X1), surfactant ratio (X2), QuR-to-lipid ratio (X3), the sonication time (X4), and the homogenization time (X5). Requirements on the maximum EE (%) and minimum PS (nm) were optimized for the preparation of QuR-SLN. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) were then used to analyze the optimized SLN and to find the crystalline state of QuR with lipid relationship. In addition, on the Caco-2 cells, at IC50 (49 µM/mL), in vitro cytotoxicity was attained.ResultsThe optimized QuR-SLN had practically spherical shapes, with % EE and a PS of 97.8 ± 1.16% and 132.16 ± 4.1 nm, respectively. In aqueous media, the degree of lipid crystallinity and the lipid modification was investigated, and the QuR incorporation and release patterns showed high correlations with both. The results showed that over 41.12 ± 1.6% of the bio-nano QuR-SLNs was released gradually over the course of 48 h, demonstrating effective QuR delayed release. Results on apoptotic observations indicate that apoptosis accounts for the majority of cell death, while necrosis, a type of cell death, constitutes a very minor portion. In conclusion, the prepared bio-nano QuR-SLNs might improve cytotoxicity and can act as an ideal carrier for the delivery of QuR and this preparation is used in the treatment of CRC.

Computational assessment of lipid facilitated membrane permeation of vancomycin using force-probe molecular dynamic simulation

In this study the efficacy of different edible lipids for drug permeation enhancement of vancomycin through biological membrane was investigated using molecular dynamic simulation. In this regard, at first the ability of the lipids for complex formation with the drug was evaluated for number of most common edible lipids including tripalmitin (TPA), trimyristin (TMY), labrafil (LAB), glycerol monostearate (GMS), glycerol monooleate (GMO), Distearoylphosphorylethanolamine (DSPE), dipalmitoylphosphatidylethanolamine (DPPE), Dipalmitoylphosphatidylcholine (DPPC), cholesterol (CL), stearic acid (SA), palmitic acid (PA) and oleic acid (OA). Then the complexes were pulled thorough a bilayer membrane while the changes in force were probed. The results showed that besides the SA, PA and OA the other examined lipids were able to perform a perfect molecular complex with the drug. Also the results of pulling simulation revealed that the least of force was needed for drug transmittance through the membrane when it was covered by LAB, TMY and DSPE. These results indicated that these lipids can be the excellent materials of choice as permeation enhancer for preparing a proper oral formulation of vancomycin. Communicated by Ramaswamy H. Sarma

Methotrexate-loaded polymeric lipid hybrid nanoparticles (PLHNPs): a reliable drug delivery system for the treatment of glioblastoma

Polymeric lipid hybrid nanoparticles (PHLNPs) are core-shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) and glyceryl tripalmitate prepared using solvent injection and homogenisation method for a glioblastoma treatment option. The MTX-loaded PLHNPs optimised by Box–Behnken design to minimise particle size, higher entrapment efficacy and maximise MTX concentration in the brain at 4 h. The particle size, entrapment efficacy, concentration of drug in the brain at 4 h, zeta potential, and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51–233.37 nm, 70.56–86.34%, 6.38–12.38 μg/mL, 25.78–36.31 mV and 1.02–5.32. In-vitro drug release studies, cellular internalisation of optimised formulation against U-87 MG shows good anticancer effects.

Crystallization-Induced Network Formation of Tri- and Monopalmitin at the Middle-Chain Triglyceride Oil/Air Interface.

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.

Construction of a Hydrogel Pectin-Based Triglyceride Optical Biosensor with Immobilized Lipase Enzymes.

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 μg. 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.

Interesterification Does Not Alter Postprandial Absorption or Oxidation of Dietary Fats, as Measured Using Stable Isotopes Analysis (P08-104-19)

ObjectivesAltering the structure of lipids by interesterification is largely replacing partial hydrogenation in the production of solid form vegetable-based fats. While proposed to be much healthier than the trans-fat containing alternatives, very little mechanistic work has been done to determine how these interesterified (IE) fats act in the human body. This study aimed to describe the physiological handling of commonly consumed IE fats during and after digestion compared to a non-IE equivalent and a control oil. MethodsIn a randomized, double-blinded controlled trial, healthy adults (n = 20) aged 45–75 years were assessed for postprandial triglyceride (TG) responses following consumption of 3 test meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate). Each meal contained 50 g of IE fat (80:20 palm stearin/palm kernel fat), the equivalent non-IE fat, or high-monounsaturated oil (canola oil, CO). A subsample of the study group (n = 9) consumed 75 mg of 1–13C glyceryl tripalmitate to trace the metabolic fate of the saturated fats consumed. Blood and breath samples were collected at baseline, and hourly thereafter for 8 h. Samples were analyzed for 13C:12C ratio by isotope ratio mass spectrometry and expressed as % dose recovered (PDR). ResultsNo differences were observed for palmitate oxidation as measured by PDR in breath CO2. Similarly, no difference in PDR of plasma 13C-palmitate in the postprandial period was observed between IE or non-IE fats (P = 0.439). Recovery of 13C-palmitate was ∼2.5-fold higher for the CO versus non-IE and IE treatments (P < 0.0001). We speculate this difference was due mainly to the differences in total solid fats at body temperature (37°C) and possibly the higher 13C-palmitate: total palmitate ratio in the CO meal. The levels of solid fat at 37°C were 21%, 16% and 0% for non-IE, IE and CO, respectively. As a function of the total palmitate found in the 50 g of fats consumed, non-IE, IE and CO were labelled with 13C palmitate at 0.26%, 0.26%, and 2.3%, respectively. While it is unlikely tracer enrichment was responsible, both factors may have collectively contributed to the higher isotope recovery in the CO meal. ConclusionsRates of palmitate absorption and oxidation were not affected by interesterification. The degree of saturation likely affect absorption due to the proportion of solid fat at body temperature. Funding SourcesBBSRC DRINC (UK). Supporting Tables, Images and/or Graphs▪▪

1-Laurin-3-Palmitin as a Novel Matrix of Solid Lipid Particles: Higher Loading Capacity of Thymol and Better Stability of Dispersions Than Those of Glyceryl Monostearate and Glyceryl Tripalmitate.

To develop solid lipid nanoparticles (SLNs) with a new lipid matrix for delivery of hydrophobic bioactive molecules, high purity 1-laurin-3-palmitin (1,3-LP) was synthesized and the prepared 1,3-LP SLNs were compared with those of two common SLN matrices in glyceryl monostearate (GMS) and glyceryl tripalmitate (PPP). Conditions of preparing SLNs were first optimized by evaluating the particle size, polydispersity index (PDI), zeta-potential, and stability. Thereafter, the performance of SLN loading of a model compound in thymol was studied. The loading capacity of thymol in 1,3-LP SLNs was 16% of lipids and higher than 4% and 12% for GMS- and PPP-SLNs, respectively. The 1,3-LP SLNs also had the best efficiency to entrapment thymol during the prolonged storage. X-ray diffraction (XRD) analyses confirmed the excellent crystalline stability of 1,3-LP leading to the stable entrapment efficiency and better stability of thymol-loaded SLNs. Conversely, the polymorphic transformation of GMS and PPP resulted in the declined entrapment efficiency of thymol in the corresponding SLNs. This work indicated the 1,3-diacylglycerol (DAG) SLNs could be used as a promising delivery system for the encapsulation of hydrophobic bioactive molecules with high loading capacity and stability.

Systematic approach for the formulation and optimization of atorvastatin loaded solid lipid NANOAPARTICLES using response surface methodology.

Atorvastatin is a lipid lowering agent with poor oral bioavailability (12%) because of poor solubility and extensive first pass hepatic metabolism. In order to overcome these issues, atorvastatin loaded solid lipid nanoparticles (ATOR-SLNs) were prepared by using glyceryl tripalmitate as lipid carrier, poloxamer 407 as surfactant and soya lecithin as emulsifier. The purpose of this work was to optimize the formulation with the application of response surface methodology to improve the physicochemical properties. The central composite rotatable design consisting of three factored factorial design with three levels was used for the optimization of the formulations. The optimized formulation was composed of drug/lipid ratio of 1:3.64, surfactant concentration of 1.5% with 5 min time for sonication. Fourier transforms infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the compatibility of drug and lipid in the formulation. The optimized ATOR- SLNs showed almost spherical shape with a mean particle size of 338.5 nm, zeta potential of -24.7mV, DL of 17.7% and EE of 81.06% respectively. The in vitro drug release study showed a burst release at the initial stage followed by the prolongation of drug release from lipid matrix. Stability study revealed that ATOR-SLNs were more stable at 4±2˚C when compared with storage at 25±2˚C/60±5% RH during the six months storage period. These results indicated that the developed ATOR-SLNs is a promising approach for increment of bioavailability by improving the physicochemical properties.

Thermal Behavior of 19F Nuclear Magnetic Resonance Signal of 19F-Containing Compound in Lipid Nano-Emulsion for Potential Tumor Diagnosis.

We developed carriers of a 19F magnetic resonance imaging (19F MRI) agent, capable of responding to the temperature difference for cancer diagnosis. The carriers were based on high melting point (mp) neutral lipids, namely, tripalmitin (TPT) and tristearin (TSR) and triarachidin (TAC). Lipid nano-emulsions (LNEs) containing a fluorine compound, i.e., a modified α-tocopherol (19F-TP), were respectively prepared as TPT-LNE, TSR-LNE, TAC-LNE1, and TAC-LNE2 and studied by 19F NMR spectroscopy. In LNE prepared with soybean oil as a control, the full width at half maximum (FWHM) values of the 19F NMR signal of 19F-TP remained constant at 25, 37, and 42°C, while those of the LNEs prepared from a neutral lipid with a high mp showed a sharp decrease between 25 and 37°C. The magnitude of the decrease followed the order: TPT-LNE < TSR-LNE < TAC-LNE1. However, TAC-LNE2, for which the amount of encapsulated 19F-TP was one third less than that of TAC-LNE1, showed a sharp decline in the FWHM between 37 and 42°C. To examine these changes, the 19F spin-lattice (T1) and spin-spin (T2) relaxation times of 19F-TP were measured. TAC-LNE2 in particular showed a substantial change in its T2 value between 37 and 42°C compared with the change of its T1 value. This result was attributed to activation of the molecular motion of 19F-TP in TAC-LNE2 from 37 to 42°C. Thus, TAC-LNE showed potential for use as a carrier for cancer diagnosis using 19F MRI.

Physicochemical Characterization of Chrysin‐Derivative‐Loaded Nanostructured Lipid Carriers with Special Reference to Anticancer Activity

AbstractHomologues long‐chain chrysin derivatives (LCD, C n: 8–18) were synthesized and incorporated into nanostructured lipid carriers (NLC) with the aim to treat human neuroblastoma. Mutual miscibility and attractive interactions among the NLC components, namely tripalmitin (TP), cetyl palmitate (CP), oleic acid (OA), and the chrysin (CHR) derivatives (LCD) at the air–water interface were assessed by the Langmuir monolayer approach. Optimum combination for the NLC formulations was found to be 2:2:1 (M/M/M) for TP/CP/OA, respectively. NLC formulations, both in the absence and presence of LCD, were characterized by combined dynamic light scattering, electron microscopy, atomic force microscopy, and differential scanning calorimetry. The size and zeta potential of the NLC formulations were found in the range 200–350 nm and −12 to −18 mV, respectively. Encapsulation efficiency and release kinetics of CHR and LCD when loaded into NLC were also evaluated. LCD exhibited maximum incorporation, drug‐loading capacity, and sustained release because of its enhanced hydrophobicity. Superior incorporation efficiency and sustained‐release profile of LCD were able to enhance their anticancer activity against human neuroblastoma cell lines, compared to CHR, making them promising agents in combating cancer.

Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers

Olanzapine is an atypical antipsychotic, undergoes extensive first pass metabolism, also has poor aqueous solubility and belongs to BCS (Biopharmaceutical Classification System) Class II drug) exhibit low oral bioavailability. To overcome this and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited through Nano structured lipid carriers (NLCs). The NLCs were formulated by solvent diffusion method using solid lipid (glyceryl tripalmitate), liquid lipid (castor oil) and surfactants (Pluronic F-68, Soylecithin). The formulated NLCs were characterized for physico-chemical properties, in-vitro release studies and in-vivo oral bioavailability. F6 has shown average particle size of 158.5 nm with PI of 0.115 indicating narrow particle size distribution and follows uni modal distribution. It was found that the batch with stearyl amine has a zeta potential of 28.39 mV which confers stability to the dispersion. Bioavailability studies indicate that there was more than 5½-fold increase in oral bioavailability in case of NLCs (F6) compared to olanzapine suspension which indicates that NLCs provided sustained release of the drugs, and these systems can be the preferred as drug carriers for lipophilic drugs in long term disease conditions such as schizophrenia for enhanced bioavailability.

Decomposition products of glycidyl esters of fatty acids by heating.

In this study, decomposition products of glycidyl palmitate (GP) of fatty acids heated at high temperature such as deep frying were investigated. When GP and tripalmitin (TP) were heated at 180 and 200°C, they were decreased with heating time. The weight of GP was less than that of TP, although both GP and TP were converted to polar compounds after heating. The decomposition rate of GP was higher than TP. Both GP and TP produced considerable amounts of hydrocarbons and aldehydes during heating. Aldehydes produced from GP and TP included saturated aldehydes with carbon chain length of 3-10, while hydrocarbons consisted of carbon chain length of 8-15. It was observed that major hydrocarbons produced from GP during heating were pentadecane. Moreover, the level of carbon dioxide (CO2) released from GP was higher than that of TP. It was suggested that fatty acids in GE might be susceptible to decarboxylation. From these results, GP might be quickly decomposed to hydrocarbons, aldehydes and CO2 besides polar compounds by heating, in comparison with TP.

Enhanced brain targeting efficacy of Olanzapine through solid lipid nanoparticles

Olanzapine (OLZ) is a typical anti-psychotic drug, which is highly lipophilic in nature, belongs to Biopharmaceutical Classification System (BCS) class II category. Though OLZ is an effective agent in the treatment of Schizophrenia, but it exhibits poor bioavailability (57%) due to extensive first-pass metabolism resulted in high dose is required to achieve therapeutic concentration in brain. Emerging evidences are indicating that high dose administration of OLZ may cause Extrapyramidal symptoms (EPS) in the psychotic patients. Hence, the present study is designed to develop Olanzapine solid lipid (OLZ-SLNs) using minimal dose of OLZ thereby enhancing the brain efficacy as well as to reduce the side effects associated with OLZ. OLZ-SLNs have been prepared by “solvent diffusion method” using lipids, such as glyceryl monostearate (GMS), tripalmitin (TP), Tween 80, and Stearyl amine as positive charge inducer. The prepared OLZ-SLNs were subjected to particle size analysis, zeta potential, and poly dispersity index measurement by using Malvern Zetasizer. Pharmacokinetics assessments of OLZ-SLNs were carried in conscious male Wistar rats through intravenous administration. Results have shown that average particle size and zeta potential of SLNs of GMS and TP were ranged from 165.1 ± 2.2 to 110.5 ± 0.5 and 35.29 ± 1.2 and 66.50 ± 0.7 mV, respectively. Relative bioavailability of OLZ in the brain was increased up to 23-fold and clearance was decreased when OLZ-SLNs while administrated intravenously. The area under the curve (AUC) and mean residence time (MRT) of OLZ-SLNs in brain were higher than OLZ suspension. These results indicate that SLNs are a promising drug delivery for OLZ. It may be an effective tool to enhance the bioavailability of OLZ in the brain with less dose administration, which could reduce the EPS associated with OLZ.

Plasma Lipid Profiles of Transgenic mice expressing the Human ApoB100XCETP are altered differentially by Diets enriched with defined Fatty Acids

Dietary fat is known to modulate plasma lipid profiles. Synthesis of high density lipoproteins (HDL), which has protective effects on vascular disease is also influenced by dietary fats, but the mechanisms are unclear. The hapoB100XCETP transgenic mouse was used to investigate the effects of fatty acids on the metabolism of plasma lipoproteins, including the pathway leading to synthesis HDL. Male transgenic mice were fed with diets formulated to provide TG (33% energy) as tripalmitin (TP), triolein (TO), tristearin (TS) or equicaloric substitution of fat with carbohydrate (sucrose) for 4 weeks. Analysis of plasma profile showed that HDL-cholesterol were 53.7+14; 64.6+8.6; 50.2+3.3; 47.0+9.2 and 45.2+4.9 mg/dL for control, oleate, palmitate, stearate and sucrose based diets, respectively. LDL-cholesterol levels were 51.7+7.0; 23.1+7.0; 38.9+2.2; 75.1+1.8 and 46.8.1.0 mg/dl, for control, TO, TP, TS and sucrose, respectively. Hepatic Lecithin-cholesterol acyltransferase (LCAT) protein levels increased by 2-fold in mice fed TS or TO diets, compared to TP, while sucrose had no effect. The scavenger receptor class B type I (SR-B1) which plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues increased in livers of animals fed TP and TO, while TS and sucrose did not have a similar effects. These results suggests that fatty acids can uniquely impact HDL, in addition, the ApoB100XCETP mouse is a useful model for the evaluation of how dietary components affect the risk of developing atherosclerosis and heart disease.

Enzymatic Interesterification of High Oleic Sunflower Oil and Tripalmitin or Tristearin

AbstractThe objective of this study was to produce low saturated, zero‐trans, interesterified fats with 20 or 30 % saturated fatty acids (SFA) such as C16:0 or C18:0. Tripalmitin (TP) or tristearin (TS) was blended with high oleic sunflower oil (HOSO) at different ratios (0.1:1, 0.3:1, and 0.5:1 [w/w]). Total C16:0 and C18:0 compositions of the resulting TP/HOSO and TS/HOSO blends, respectively, were plotted against blending ratios. Linear interpolation was used to estimate blending ratios that would yield physical blends (PB) with 20 or 30 % SFA. Interesterified blends (IB) were then synthesized from the customized PB using Lipozyme TL IM as the biocatalyst. Total and sn‐2 fatty acid compositions, triacylglycerol (TAG) molecular species, thermal behavior, and oxidative stability of PB and IB were compared. The total fatty acid compositions of PB and IB were similar but fatty acid positional distributions and TAG molecular species composition differed. IB contained 5–10 % more SFA at the sn‐2 position than corresponding PB. Furthermore, interesterification generated mono‐ and disaturated TAG species which resulted in broader melting profiles for IB. However, IB had lower oxidative stability than PB. The reformulation of food products with zero‐trans interesterified fats may be advantageous to the reduction of cardiovascular disease burden in the population.

Effect of dietary lipid on the growth, fatty acid composition and Δ5 Fads expression of abalone (Haliotis discus hannai Ino) hepatopancreas

This study investigated the effect of dietary lipid on the growth, fatty acid composition and Δ5 fatty acyl desaturase genes (Fads) expression of juvenile abalone (Haliotis discus hannai Ino) hepatopancreas. Six purified diets were formulated to contain tripalmitin (TP), olive oil (OO, 72.87% 18:1n-9), grape seed oil (GO, 68.67% 18:2n-6), linseed oil (LO, 70.48% 18:3n-3), ARA oil (AO, 41.81% ARA) or EPA oil (EO, 44.09% EPA and 23.67% DAH). No significant difference in survival rate was observed among abalone fed with different diets. Weight gain rate (WGR) and daily growth rate of shell length (DGR SL) were significantly increased in abalone fed with diets containing OO, AO and EO, but decreased in abalone fed with LO diet (P < 0.05) in comparison with those fed with TP. High level of dietary 18:2n-6 resulted in higher content of n-6 polyunsaturated fatty acids (PUFAs) in abalone fed with GO than those fed with TP, OO, LO and EO (P < 0.05). n-3 PUFAs in abalone fed with LO was significantly higher than those in abalone fed with TP, OO, GO and AO (P < 0.05). The highest contents of 20:1n-9 and 22:1n-9 were observed in abalone fed with OO. The expression of Δ5 Fads in hepatopancreas of abalone was enhanced by high concentration of 18:3n-3 and suppressed by dietary LC-PUFAs; however it was not affected by dietary high concentration of 18:1n-9 or 18:2n-6. These results provided valuable information for understanding the synthesis of LC-PUFAs and nutritional regulation of Δ5 Fads expression in abalone.

Influence of surfactant and lipid type on the physicochemical properties and biocompatibility of solid lipid nanoparticles.

Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around −11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results.

In vitro comparative evaluation of monolayered multipolymeric films embedded with didanosine-loaded solid lipid nanoparticles: a potential buccal drug delivery system for ARV therapy

Drug delivery via the buccal route has emerged as a promising alternative to oral drug delivery. Didanosine (DDI) undergoes rapid degradation in the gastrointestinal tract, has a short half-life and low oral bioavailability, making DDI a suitable candidate for buccal delivery. Recent developments in buccal drug delivery show an increased interest toward nano-enabled delivery systems. The advantages of buccal drug delivery can be combined with that of nanoparticulate delivery systems to provide a superior delivery system. The aim of this study was to design and evaluate the preparation of novel nano-enabled films for buccal delivery of DDI. Solid lipid nanoparticles (SLNs) were prepared via hot homogenization followed by ultrasonication and were characterized before being incorporated into nano-enabled monolayered multipolymeric films (MMFs). Glyceryl tripalmitate with Poloxamer 188 was identified as most suitable for the preparation of DDI-loaded SLNs. SLNs with desired particle size (PS) (201 nm), polydispersity index (PDI) (0.168) and zeta potential (−18.8 mV) were incorporated into MMFs and characterized. Conventional and nano-enabled MMFs were prepared via solvent casting/evaporation using Eudragit RS100 and hydroxypropyl methylcellulose. Drug release from the nano-enabled films was found to be faster (56% versus 20% in first hour). Conventional MMFs exhibited higher mucoadhesion and mechanical strength than nano-enabled MMFs. SLNs did not adversely affect the steady state flux (71.63 ± 13.54 µg/cm2 h versus 74.39 ± 15.95 µg/cm2 h) thereby confirming the potential transbuccal delivery of DDI using nano-enabled MMFs. Nano-enabled buccal films for delivery of DDI can be successfully prepared, and these physico-mechanical studies serve as a platform for future formulation optimization work in this emerging field.

Preparation and Characterization of Protein-loaded Lipid-polymer Hybrid Nanoparticles with Polycaprolactone as Polymeric Core Material

Lipid–polymer hybrid nanoparticles (LPNs) have emerged as a potent therapeutic nano-carrier alternative to liposomes and polymeric nanoparticles. In this work, lipid–polymer hybrid nanoparticles were prepared using polycaprolactone, phosphatidylcholine: glyceryl tripalmitate mixture and lysozyme as the polymer, lipids and model protein, respectively. Uniform nanoparticles with about 100 nm in size were obtained using the modified emulsification solvent evaporation method. The results indicated that LPNs showed higher encapsulation efficiency compared with naked polycaprolactone nanoparticles. According to the results of bioactivity assay, 63.86% bioactive lysozyme was recovered from the LPNs. These results indicated that modification of polycaprolactone nanoparticles with lipids could considerably increase the drug-delivery efficiency and LPNs had potential in the delivery of peptides and proteins.

Methods of analysis for 2-dodecylcyclobutanone and studies to support its role as a unique marker of food irradiation

Methods of analysis for 2-dodecylcyclobutanone (2-DCB) using gas chromatography with mass spectrometric detection (GC–MS), liquid chromatography with time-of-flight mass spectrometric detection (LC–TOF-MS) and LC with tandem MS (MS/MS) detection have been developed and optimised for maximum sensitivity to allow very low irradiation doses to be detected. The LC–MS/MS method, following derivatisation with 2,4-dinitrophenylhydrazine, was found to be the most sensitive technique and was used to determine the amount of 2-DCB formed from the model compounds palmitic acid, glyceryl tripalmitate and 1,3-dipalmitoyl-2-oleoylglycerol irradiated over a range of doses by two different irradiation sources (gamma and electron beam). The model compounds were also treated with a number of non-irradiation based processing techniques including heating in the presence and absence of oxygen, light, and redox active metal salts, in a conventional oven, microwave oven and pressure cooker. No 2-DCB was detected in any of the processed non-irradiated model compounds, reaffirming the hypothesis that 2-DCB is a unique radiolytic product that can be used as a marker of irradiation in foodstuffs.