Complexity of confined water vitrification and its glass transition temperature.

The ability of vitrification when crossing the glass transition temperature (Tg) of confined and bulk water is crucial for myriad phenomena in diverse fields, ranging from the cryopreservation of organs and food to the development of cryoenzymatic reactions, frost damage to buildings, and atmospheric water. However, determining water's Tg remains a major challenge. Here, we elucidate the glass transition of water by analyzing the calorimetric behavior of nano-confined water across various pore topologies (diameters: 0.3 to 2.5 nm). Our approach involves subjecting confined water to annealing protocols to identify the temperature and time evolution of nonequilibrium glass kinetics. Furthermore, we complement this calorimetric approach with the dynamics of confined water, as seen by broadband dielectric spectroscopy and linear calorimetric measurements, including the fast scanning technique. This study demonstrated that confined water undergoes a glass transition in the temperature range of 170 to 200 K, depending on the confinement size and the interaction with the confinement walls. Moreover, we also show that the thermal event observed at ~136 K must be interpreted as an annealing prepeak, also referred to as the "shadow glass transition." Calorimetric measurements also allow the detection of a specific heat step above 200 K, which is insensitive to annealing and, thereby, interpreted as a true thermodynamic transition. Finally, by connecting our results to bulk water behavior, we offer a comprehensive understanding of confined water vitrification with potential implications for numerous applications.

A retrospective study of resting energy expenditure in children hospitalized with different nutritional status.

Background: Resting energy expenditure (REE) refers to the energy consumption of the body in a resting state without skeletal muscle activity. This study aimed to examine the REE among children hospitalized with varying nutritional status. Methods: This was a retrospective study. We enrolled 109 pediatric cases that underwent indirect calorimetry (IC) and divided into four groups: mild malnutrition group (15 cases), moderate malnutrition group (30 cases), severe malnutrition group (32 cases), and obesity group (32 cases). We compared and analyzed the measured REE (mREE) using IC with the predicted REE (pREE) using five energy equations. The paired t-test was used to compare the results of two samples. Pearson analysis was used to assess the correlation between two values. The agreement analysis was performed using the Bland-Altman method. Results: There was no significant difference in mREE between the mild, moderate, and severe malnutrition groups, but each differed significantly from the obesity group. All populations exhibited significant correlation between the mREEs and all five energy equations, and the equation with the highest predictive accuracy was the Schofield equation, which achieved an accuracy of 47.7%. In subgroup analysis, there was no significant difference between mREE and pREE for each of the five equations in the mild, moderate malnutrition groups. Only the prediction result of the Liu equation was not significantly different from the mREE in the severe malnutrition group. The prediction accuracy of the Liu equation was relatively the highest (34.4%). However, in the obese group, there were significant differences in pREE and mREE between the Liu equation and Mifflin equation. Under different nutritional statuses, the results of the Bland-Altman analysis suggested that deviation values between REEs predicted by each equation and mREE were greater than ±10%. Conclusions: There were differences in REE among children with different nutritional status. The results obtained from the five predictive energy equations deviated from the IC results. When REE cannot be measured by IC, it is essential to choose an appropriate predictive energy equation based on the nutritional status of the individual.

Energy utilization in lactating Jersey cows consuming a mixture of DDGS and straw replacing alfalfa hay.

Some forages require significant amounts of water to grow, causing the dairy industry to be dependent on a limited resource. Feeding crop residues and feed coproducts in dairy rations may represent opportunities when alfalfa is not readily available, and to reduce the industry's use of water. A study using indirect calorimetry and 12 multiparous lactating Jersey cows (BW = 447.5 ± 43.7 kg; DIM = 71 ± 11 d, mean ± SD) was conducted to determine the effect of feeding dried distillers grains and solubles (DDGS) and straw in replacement of alfalfa hay on milk production and energy utilization. A triplicated 4 × 4 Latin square design was used to evaluate the replacement of alfalfa hay with a coproduct mixture (COP) of wheat straw and DDGS. Animals were blocked by milk yield and randomly assigned to 1 of 4 experimental treatments including (proportions on a DM basis): a control diet (CON) containing 18.2% of alfalfa hay, a low-coproduct diet (LCOP) that contained 8.1% of COP, a medium-coproduct diet (MCOP) that contained 16.3% of COP, and a high-coproduct diet (HCOP) that contained 24.3% of COP. No differences were observed for daily dry matter intake or milk yield (mean ± SEM) 19.5 kg ± 0.60, 29.6 kg ± 0.91, respectively. A quadratic tendency was observed where increasing inclusion of COP up to 16.3% maintained ECM and milk fat yield but decreased when animals were fed 24.3% COP. Total methane production decreased linearly from 429.4 to 345.0 ± 22.8 L/d from CON to HCOP diets, respectively. The digestibility of CP increased linearly from 64.0 to 70.4 ± 0.95% and N balance increased linearly from 43.3 to 90.7 ± 15.0 g/d in animals consuming CON to HCOP diets. Total time spent ruminating was lowest in animals consuming the HCOP diet. A linear increasing tendency in digestible and metabolizable energy of 2.92 to 3.02 ± 0.041 Mcal/kg and 2.58 to 2.70 ± 0.047 Mcal/kg was observed in animals consuming CON to HCOP. The proportion ME from DE (ME/DE) tended to linearly increase from 88.3 to 89.4 ± 0.454 when COP was added to the diet. Results of this study indicate that alfalfa hay with a mixture of straw and DDGS can maintain milk production and DMI, but the partial or full replacement of alfalfa with the COP mixture may result in differences in energy utilization in part driven by effects on CH4 reduction.

Author Response: Emphasizing Patient-centered Outcomes and Improved Exclusion Criteria in Randomized Control Trials for Clinical Nutrition in ICU.

How to cite this article: Govil D, Chandrasekaran A, Pachisia AV, Harne R, Patel SJ, Pal D. Author Response: Emphasizing Patient-centered Outcomes and Improved Exclusion Criteria in Randomized Control Trials for Clinical Nutrition in ICU. Indian J Crit Care Med 2024;28(8):806-807.

Emphasizing Patient-centered Outcomes and Improved Exclusion Criteria in Randomized Controlled Trials for Clinical Nutrition in Critically Ill Patients.

How to cite this article: Sundarsingh V, Kumar M. Emphasizing Patient-centered Outcomes and Improved Exclusion Criteria in Randomized Controlled Trials for Clinical Nutrition in Critically Ill Patients. Indian J Crit Care Med 2024;28(8):804-805.

The effect of cobalt alloying on the phase transformation kinetics of Ni-Ti alloys.

This study investigates the influence of cobalt (Co) alloying addition and heat treatment temperature on the phase transformation behaviour controlling the superelasticity and shape memory effect (SME) of Nickel-Titanium (Ni-Ti) alloys, commonly known as nitinol. The microstructural evolution upon heat treatment conducted at a temperature ranging from 440 to 560 °C was thoroughly analyzed via Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS). Increase in heat treatment temperatures from 470 °C up to 530 °C led to the dissolution of particles present in as-received (cold-worked) condition. It was determined that Co addition into the Ni-Ti alloy system resulted in a change in the nucleation and growth kinetics of Ti-rich precipitates, leading to the formation of larger and fewer particles during processing. Both binary and ternary alloys showed a decrease in austenite finish temperature (Af) with increasing heat treatment temperatures, however, the rate of decrease was found to be higher for Co containing ternary alloys. This is linked with faster structural relaxation when Co is present and evidenced by lattice size variation during heat treatment. It is highlighted that heat treatment methodology needs to be tailored to the specific alloy composition for controlling superelasticity and SME via alloy design.

The overlapping of phenotypes in Wiedemann-Steiner, Kleefstra and Coffin-Siris syndromes: a study of eleven patients.

BACKGROUND: Some chromatinopathies may present with common clinical findings (intellectual disability, brain and limb malformation, facial dysmorphism). Furthermore, one of their cardinal shared features is growth dysregulation.We aimed to assess and deepen this resemblance in three specific conditions, namely Wiedemann-Steiner (WDSTS), Kleefstra (KLEFS1) and Coffin-Siris syndrome (CSS1), with a particular focus on possible metabolic roots. METHODS: Eleven patients were enrolled, three with WDSTS, five with KLEFS1 and three with CSS1, referring to Fondazione IRCCS Ca' Granda Ospedale Maggiore, Milan, Italy. We performed both a physical examination with detailed anthropometric measurements and an evaluation of the patients' REE (rest energy expenditure) by indirect calorimetry, comparing the results with age- and sex-matched healthy controls. RESULTS: We observed new clinical features and overlap between these conditions suggesting that different disturbances of epigenetic machinery genes can converge on a common effect, leading to overlapping clinical phenotypes.The REE was not distinguishable between the three conditions and healthy controls. CONCLUSIONS: Epigenetic machinery plays an essential role both in growth regulation and in neurodevelopment; we recommend evaluating skeletal [craniovertebral junction abnormalities (CVJ) polydactyly], otolaryngological [obstructive sleep apnea syndrome (OSAs), recurrent otitis media], dental [tooth agenesis, talon cusps], and central nervous system (CNS) [olfactory bulbs and cerebellum anomalies] features. These features could be included in monitoring guidelines. Further studies are needed to deepen the knowledge about energy metabolism.

Whole-body volume of oxygen consumption while walking: Agreement between measured and estimated values.

Predictive equations are widely employed for estimating the volume of oxygen consumption (VO2) while walking, which is ultimately employed to determine energy expenditure and tailor exercise prescription. This study aimed to test the agreement between the measured VO2 and estimated VO2 during a walking protocol on a treadmill at 3.5, 4.5, 5.5, and 6.5 km/h. Thirty-eight young adults (50% women) participated in this cross-sectional study. The Omnical (Maastricht Instruments, Maastricht, The Netherlands) and K5 (Cosmed, Rome, Italy) metabolic systems were used to measure VO2. To determine the predictive equations, a comprehensive literature search was conducted using the MEDLINE database from May 2022 to July 2023. Seven predictive equations were found and included for estimating VO2 values. We calculated the mean bias (mean difference between measured VO2 and estimated VO2) obtained at each speed using one-sample t-tests. We compared the VO2 measured and estimated values using repeated measures analysis of variance and the Bland-Altman method. One-sample t-tests showed that all score errors were different from zero (ranging from 1.1 to 5.4 mL/kg/min). Thus, no predictive equation estimated similar VO2 values in comparison with the Omnical and K5 metabolic systems at all intensities. However, the Weyand equation showed the lowest bias across all intensities (score error of 1.1 mL/kg/min). This study showed a lack of agreement between the Omnical and K5 systems compared to diverse predictive equations specially designed to estimate VO2 during walking. Nevertheless, based on our results, the Weyand equation should be the preferred option.

Use of Differential ScanninTableg Calorimetry as a Rapid, Effective In-process Check Method for Impurity Quantitation of an Early Clinical Batch of Giredestrant (GDC-9545).

Giredestrant (GDC-9545) is a selective estrogen receptor degrader (SERD) that was developed for treatment of ER+/HER2- metastatic breast cancer. An anhydrous crystalline tartrate salt was identified as the solid form suitable for clinical development. An early clinical batch of the active pharmaceutical ingredient (API)/drug substance failed to pass the GMP purity specifications owing to the presence of a substantial amount of high molecular weight impurities (oligomers), as determined by size exclusion chromatography. Several trial rework batches were manufactured using various re-slurry and recrystallization conditions to purge impurities in the drug substance to adhere to purity specifications. Based on the melting point depression of the API in presence of oligomers in these rework batches, a differential scanning calorimetry method was developed to quantify impurity content as a function of melting point onset of the API. This thermal analysis method was used as a surrogate for chromatography as a rapid, effective in-process check method for impurity quantitation to enable the timely release of the final reworked clinical batch. Post release, the % w/w oligomer value determined by calorimetry was in excellent agreement to that obtained by size exclusion chromatography.

Solvation free energy in governing equations for DNA hybridization, protein-ligand binding, and protein folding.

This work examines the thermodynamics of model biomolecular interactions using a governing equation that accounts for the participation of bulk water in the equilibria. In the first example, the binding affinities of two DNA duplexes, one of nine and one of 10 base pairs in length, are measured and characterized by isothermal titration calorimetry (ITC) as a function of concentration. The results indicate that the change in solvation free energy that accompanies duplex formation (ΔGS) is large and unfavorable. The duplex with the larger number of G:C pairings yields the largest change in solvation free energy, ΔGS = +460 kcal·mol-1per base pair at 25 °C. A van't Hoff analysis of the data is complicated by the varying degree of intramolecular base stacking within each DNA strand as a function of temperature. A modeling study reveals how the solvation free energy alters the output of a typical ITC experiment and leads to a good, though misleading, fit to the classical equilibrium equation. The same thermodynamic framework is applied to a model protein-ligand interaction, the binding of ribonuclease A with the nucleotide inhibitor 3'-UMP, and to a conformational equilibrium, the change in tertiary structure of α-lactalbumin in molar guanidinium chloride solutions. The ribonuclease study yields a value of ΔGS = +160 kcal·mol-1, whereas the folding equilibrium yields ΔGS ≈ 0, an apparent characteristic of hydrophobic interactions. These examples provide insight on the role of solvation energy in binding equilibria and suggest a pivot in the fundamental application of thermodynamics to solution chemistry.

Relationship between energetic gap and sensitivity to anti-programmed cell death 1 immune checkpoint inhibitors in non-small cell lung cancer patients: The ELY-2 study.

BACKGROUND & AIMS: We previously reported in the ELY prospective study that increased resting energy expenditure (REE) - so-called hypermetabolism - worsened tumor response, 6-month progression-free (PFS) and overall survival (OS) in metastatic non-small cell lung cancer (mNSCLC) patients treated with immune checkpoint inhibitors (ICI). Here, we investigated the effect of caloric coverage on the sensitivity to ICI. METHODS: We retrospectively analysed a multicentric database of mNSCLC patients treated with ICI. All patients had a baseline nutritional assessment including REE measured with indirect calorimetry and a dietitian estimation of food intakes. Measured/theoretical REE ≥110% defined hypermetabolism. Intakes ≥90% of estimated needs defined caloric coverage. The primary endpoint was PFS. Secondary endpoints included response rate and OS. RESULTS: Among 162 patients, 84 (51.9%) were normometabolic, and 78 (48.1%) hypermetabolic. In hypermetabolic patients, 40 (51.3%) met their caloric needs (group A) while 38 (48.7%) did not (group B). Median PFS was 4.3 vs. 1.9 months in groups A and B, respectively (HR: 0.49, 95%CI [0.31-0.80], p = 0.004). The PFS achieved in the group A and in normometabolic patients were similar (HR: 0.99, 95%CI [0.65-1.51], p = 0.95). In multivariate analysis, caloric coverage was independently associated with improved PFS in hypermetabolic patients (HR: 0.56, 95%CI [0.31-0.99], p = 0.048). Among hypermetabolic patients, the median OS was higher in the group A (HR: 0.58, 95%CI [0.35-0.95], p = 0.03). CONCLUSION: Energy supply is a critical determinant of the sensitivity to ICI in NSCLC patients. A randomized study to evaluate the benefit of early nutritional intervention is warranted.

Oxidative Stability of Fish Oil-Loaded Nanocapsules Produced by Electrospraying Using Kafirin or Zein Proteins as Wall Materials.

The encapsulation of fish oil by monoaxial electrospraying using kafirin or zein proteins as hydrophobic wall materials was investigated. Kafirin resulted in spherical fish oil-loaded nanocapsules (>50% of capsules below 1 µm), whereas zein led to fish oil-loaded nanocapsules with non-spherical morphology (>80% of capsules below 1 µm). Both hydrophobic encapsulating materials interacted with fish oil, successfully entrapping the oil within the protein matrix as indicated by Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopy results. FTIR also suggested hydrogen bonding between fish oil and the proteins. Trapped radicals in the encapsulation matrix that were detected by electron paramagnetic resonance (EPR), indicated oxidation during electrospraying and storage. Results from isothermal (140 °C) differential scanning calorimetry (DSC) denoted that the encapsulation of fish oil by electrospraying using both kafirin or zein as wall materials protected fish oil from oxidation. In particular, the zein-based nanocapsules were 3.3 times more oxidatively stable than the kafirin-based nanocapsules, which correlates with the higher oil encapsulation efficiency found for zein-based capsules. Thus, this study shows that kafirin might be considered a hydrophobic wall material for the encapsulation of fish oil by electrospraying, although it prevented lipid oxidation to a lower extent when compared to zein.

New, Optimized Skin Calorimeter Version for Measuring Thermal Responses of Localized Skin Areas during Physical Activity.

We present an optimized version of the skin calorimeter for measuring localized skin thermal responses during physical activity. Enhancements include a new holding system, more sensitive thermopiles, and an upgraded spiked heat sink for improved efficiency. In addition, we used a new, improved calorimetric model that takes into account all the variables that influence the measurement process. Resolution in power measurement is 1 mW. Performance tests under air currents and movement disturbances showed that the device maintains high accuracy; the deviation produced by these significant disturbances is less than 5%. Human subject tests, both at rest and during exercise, confirmed its ability to accurately measure localized skin heat flux, heat capacity, and thermal resistance (less than 5% uncertainty). These findings highlight the calorimeter's potential for applications in sports medicine and physiological studies.

Synergetic Effect of ß-Cyclodextrin and Its Simple Carbohydrate Substituents on Complexation of Folic Acid and Its Structural Analog Methotrexate.

Folic acid (FA) and its structural analog, anticancer medicine methotrexate (MTX), are known to form host/guest complexes with native cyclodextrins, of which the most stable are formed with the medium-sized ß-cyclodextrin. Based on our research, proving that simple sugars (D-glucose, D-galactose, and D-mannose) can form adducts with folic acid, we envisioned that combining these two types of molecular receptors (cyclodextrin and simple carbohydrates) into one may be beneficial for the complexation of FA and MTX. We designed and obtained host/guest inclusion complexes of FA and MTX with two monoderivatives of ß-cyclodextrin-substituted at position 6 with monosaccharide (glucose, G-ß-CD) and disaccharide (maltose, Ma-ß-CD). The complexation was proved by experimental (NMR, UV-vis, IR, TG, DSC) and theoretical methods. We proved that derivatization of ß-cyclodextrin with glucose and maltose has a significant impact on the complexation with FA and MTX, as the addition of one glucose subunit to the structure of the receptor significantly increases the value of association constant for both FA/G-ß-CD and MTX/G-ß-CD, while further extending a pendant chain (incorporation of maltose subunit) results in no additional changes.

Comparative Studies for Cryopreservation of Agave Shoot Tips by Droplet-Vitrification.

The objective of this work was to assess the suitability of the Droplet-vitrification protocol previously developed with Agave peacockii shoot tips for the cryopreservation of six Agave species. Shoot tips were precultured for 1 day on a medium with 0.3 M sucrose in the dark, loaded in a solution with 1.6 M glycerol and 0.4 M sucrose for 20 min, and dehydrated by exposure to Plant Vitrification Solution 2 (PVS2) at 0 °C for 20 min. Complementary studies using histological analysis, Differential scanning calorimetry (DSC), and evaluation of morphological characteristics in cryo-derived plants were performed. Survival rates ranged from 84% to 100% and from 76% to 97% before and after cryopreservation regardless of the Agave species belonging to two taxonomic subgenera. Thermal analysis of shoot tips subjected to the successive steps of the Droplet-vitrification protocol identified ice crystal formation after loading treatment and glass transition after osmotic dehydration with PVS2. The average glass transition temperature (Tg) was -55.44 °C based on the results of four Agave species. The histological studies showed the anatomical differences that could be found in the meristematic structures depending on the loss of apical dominance. This is the most advanced research on cryopreservation of Agave shoot tips.

Sum of Skinfold-Corrected Girths Correlates with Resting Energy Expenditure: Development of the NRGCO Equation.

Our study aimed to validate existing equations and develop the new NRGCO equation to estimate resting energy expenditure (REE) in the Colombian population with moderate-to-high physical activity levels. Upon satisfying the inclusion criteria, a total of 86 (43F, 43M) healthy adults (mean [SD]: 27.5 [7.7] years; 67.0 [13.8] kg) were evaluated for anthropometric variables and REE by indirect calorimetry using wearable gas analyzers (COSMED K4 and K5). Significant positive correlations with REE were found for body mass (r = 0.65), body mass-to-waist (r = 0.58), arm flexed and tensed girth (r = 0.66), corrected thigh girth (r = 0.56), corrected calf girth (r = 0.61), and sum of breadths (∑3D, r = 0.59). As a novelty, this is the first time a significant correlation between REE and the sum of corrected girths (∑3CG, r = 0.63) is reported. Although existing equations such as Harris-Benedict (r = 0.63), Mifflin-St. Jeor (r = 0.67), and WHO (r = 0.64) showed moderate-to-high correlations with REE, the Bland-Altman analysis revealed significant bias (p < 0.05), indicating that these equations may not be valid for the Colombian population. Thus, participants were randomly distributed into either the equation development group (EDG, n = 71) or the validation group (VG, n = 15). A new model was created using body mass, sum of skinfolds (∑8S), corrected thigh, corrected calf, and age as predictors (r = 0.755, R2 = 0.570, RMSE = 268.41 kcal). The new NRGCO equation to estimate REE (kcal) is: 386.256 + (24.309 × BM) - (2.402 × ∑8S) - (21.346 × Corrected Thigh) + (38.629 × Corrected Calf) - (7.417 × Age). Additionally, a simpler model was identified through Bayesian analysis, including only body mass and ∑8S (r = 0.724, R2 = 0.525, RMSE = 282.16 kcal). Although external validation is needed, our validation resulted in a moderate correlation and concordance (bias = 91.5 kcal) between measured and estimated REE values using the new NRGCO equation.

Characterization of Cationic Amino Acid Binding Protein from Candidatus Liberibacter Asiaticus and in Silico Study to Identify Potential Inhibitor Molecules.

Cationic amino acid binding protein (CLasArgBP), one of the two amino acid binding receptor in Candidatus Liberibacter asiaticus (CLas), is predominately expressed in citrus psyllids as a part of ATP-binding cassette transport system. The present study describes characterization of CLasArgBP by various biophysical techniques and in silico study, to identify potential inhibitor molecules against CLasArgBP through virtual screening and MD simulations. Further, in planta study was carried out to assess the effect of selected inhibitors on Huanglongbing infected Mosambi plants. The results showed that CLasArgBP exhibits pronounced specificity for arginine, histidine and lysine. Surface plasmon resonance (SPR) study reports highest binding affinity for arginine (Kd, 0.14 µM), compared to histidine and lysine (Kd, 15 µΜ and 26 µΜ, respectively). Likewise, Differential Scanning Calorimetry (DSC) study showed higher stability of CLasArgBP for arginine, compared to histidine and lysine. N(omega)-nitro-L-arginine, Gamma-hydroxy-L-arginine and Gigartinine emerged as lead compounds through in silico study displaying higher binding energy and stability compared to arginine. SPR reports elevated binding affinities for N(omega)-nitro-L-arginine and Gamma-hydroxy-L-arginine (Kd, 0.038 µΜ and 0.061 µΜ, respectively) relative to arginine. DSC studies showed enhanced thermal stability for CLasArgBP in complex with selected inhibitors. Circular dichroism and fluorescence studies showed pronounced conformational changes in CLasArgBP with selected inhibitors than with arginine. In planta study demonstrated a substantial decrease in CLas titer in treated plants as compared to control plants. Overall, the study provides the first comprehensive characterization of cationic amino acid binding protein from CLas, as a potential drug target to manage HLB disease.

Unveiling the multifaceted interactions of antitumor drug mitoxantrone with ct-DNA through biophysical and in silico studies.

Mitoxantrone, an anthraquinone derivative, is a widely used anticancer drug with its well-known ability to engage in complex interactions with DNA. Although known for its intercalating ability, the enigma surrounding its binding modes with DNA persists. The existing corpus of literature primarily focuses on mitoxantrone-DNA interactions with short DNA sequences, thereby yielding insights into its interactive nature is limited to this specific sequence. This study aims to elucidate the diverse modes with which mitoxantrone interacts with calf thymus DNA using a combination of spectroscopy, calorimetry and in silico studies. The findings from spectroscopic, calorimetric and molecular dynamic results in correlation with existing literature, unveil a fascinating narrative: mitoxantrone intercalates at lower concentrations but promotes condensation at higher concentrations. Although intercalation with side chains positioned in the minor/major groove is the major binding mode in GC-rich sequences, molecular modelling studies hint at an alternative binding mode in AT-rich sequences where it exclusively displays pure electrostatic interaction. These findings underscore the pivotal role of both drug structure and base sequence in dictating binding mode and affinity. Such insights not only deepen the understanding of structure-activity relationships but also hold promise for guiding future drug design strategies.

Structure and Characterization of Catanionic Complexes and Biocompatible Vesicles of N-Acyltaurine and Sarcosine Alkyl Ester: Encapsulation and Release Studies with 5-Fluorouracil.

Hydrated dispersions containing equimolar mixtures of cationic and anionic amphiphiles, referred to as catanionic systems, exhibit synergistic physicochemical properties, and mixing single-chain cationic and anionic lipids can lead to the spontaneous formation of vesicles as well as other phase structures. In the present work, we have characterized two catanionic systems prepared by mixing N-acyltaurines (NATs) and sarcosine alkyl esters (SAEs) bearing 11 and 12 C atoms in the acyl/alkyl chains. Turbidimetric and isothermal titration calorimetric studies revealed that both NATs form equimolar complexes with SAEs having matching acyl/alkyl chains. The three-dimensional structure of the sarcosine lauryl ester (lauryl sarcosinate, LS)-N-lauroyltaurine (NLT) equimolar complex has been determined by single-crystal X-ray diffraction. The LS-NLT equimolar complex is stabilized by electrostatic attraction and multiple hydrogen bonds, including classical, strong N-H···O hydrogen bonds as well as several C-H···O hydrogen bonds between the two amphiphiles. DSC studies showed that both equimolar complexes show single sharp phase transitions. Transmission electron microscopy and dynamic light scattering studies have demonstrated that the LS-NLT catanionic complex assemblies yield stable medium-sized vesicles (diameter 280-350 nm). These liposomes were disrupted at high pH, suggesting that the designed catanionic complexes can be used to develop base-labile drug delivery systems. In vitro studies with these catanionic liposomes showed efficient entrapment (73% loading) and release of the anticancer drug 5-fluorouracil in the physiologically relevant pH range of 6.0-8.0. The release rate was highest at pH 8.0, reaching about 78%, 90%, and 100% drug release at 2, 6, and 12 h, respectively. These observations indicate that LS-NLT catanionic vesicles will be useful for designing drug delivery systems, particularly for targeting organs such as the colon, which are inherently at basic pH.