Head-to-Head Comparison of Caco-2 Transwell and Gut-on-a-Chip Models for Assessing Oral Peptide Formulations.

Oral delivery of potent peptide drugs provides key formulation challenges in the pharmaceutical industry: stability, solubility, and permeability. Intestinal permeation enhancers (PEs) can overcome the low oral bioavailability by improving the drug permeability. Conventional in vitro and ex vivo models for assessing PEs fail to predict efficacy in vivo. Here, we compared Caco-2 cells cultured in the conventional static Transwell model to a commercially available continuous flow microfluidic Gut-on-a-Chip model. We determined baseline permeability of FITC-Dextan 3 kDa (FD3) in Transwell (5.3 ± 0.8 × 10-8 cm/s) vs Chip (3.2 ± 1.8 × 10-7 cm/s). We screened the concentration impact of two established PEs sodium caprate and sucrose monolaurate and indicated a requirement for higher enhancer concentration in the Chip model to elicit equivalent efficacy e.g., 10 mM sodium caprate in Transwells vs 25 mM in Chips. Fasted and fed state simulated intestinal fluids (FaSSIF/FeSSIF) were introduced into the Chip and increased basal FD3 permeability by 3-fold and 20-fold, respectively, compared to 4-fold and 4000-fold in Transwells. We assessed the utility of this model to peptides (Insulin and Octreotide) with PEs and observed much more modest permeability enhancement in the Chip model in line with observations in ex vivo and in vivo preclinical models. These data indicate that microfluidic Chip models are well suited to bridge the gap between conventional in vitro and in vivo models.

Preparation and Application of Decanoic Acid/Arginine Hydrogels to a Transdermal Formulation.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Prebiotic Membranes and Micelles Do Not Inhibit Peptide Formation During Dehydration.

Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first protocells would have hinged upon colocalization of these biopolymers with fatty acid membranes. Using atomic force microscopy, we find that a prebiotic fatty acid (decanoic acid) forms stacks of membranes after dehydration. Using LC-MS-MS (liquid chromatography-tandem mass spectrometry) with isotope internal standards, we measure the rate of formation of serine dipeptides. We find that dipeptides form during dehydration at moderate temperatures (55 °C) at least as fast in the presence of decanoic acid membranes as in the absence of membranes. Our results are consistent with the hypothesis that protocells could have formed within evaporating environments on the early Earth.

Impact of Intestinal Concentration and Colloidal Structure on the Permeation-Enhancing Efficiency of Sodium Caprate in the Rat.

In this work, we set out to better understand how the permeation enhancer sodium caprate (C10) influences the intestinal absorption of macromolecules. FITC-dextran 4000 (FD4) was selected as a model compound and formulated with 50-300 mM C10. Absorption was studied after bolus instillation of liquid formulation to the duodenum of anesthetized rats and intravenously as a reference, whereafter plasma samples were taken and analyzed for FD4 content. It was found that the AUC and Cmax of FD4 increased with increasing C10 concentration. Higher C10 concentrations were associated with an increased and extended absorption but also increased epithelial damage. Depending on the C10 concentration, the intestinal epithelium showed significant recovery already at 60-120 min after administration. At the highest studied C10 concentrations (100 and 300 mM), the absorption of FD4 was not affected by the colloidal structures of C10, with similar absorption obtained when C10 was administered as micelles (pH 8.5) and as vesicles (pH 6.5). In contrast, the FD4 absorption was lower when C10 was administered at 50 mM formulated as micelles as compared to vesicles. Intestinal dilution of C10 and FD4 revealed a trend of decreasing FD4 absorption with increasing intestinal dilution. However, the effect was smaller than that of altering the total administered C10 dose. Absorption was similar when the formulations were prepared in simulated intestinal fluids containing mixed micelles of bile salts and phospholipids and in simple buffer solution. The findings in this study suggest that in order to optimally enhance the absorption of macromolecules, high (≥100 mM) initial intestinal C10 concentrations are likely needed and that both the concentration and total dose of C10 are important parameters.

Ultrasound-assisted dispersive liquid-phase microextraction by solidifying L-menthol-decanoic acid hydrophobic deep eutectic solvents for detection of five fungicides in fruit juices and tea drinks.

An ecofriendly and efficient ultrasound-assisted deep eutectic solvents dispersive liquid-phase microextraction by solidifying the deep eutectic solvents-rich phase was developed to determine azoxystrobin, fludioxonil, epoxiconazole, cyprodinil, and prochloraz in fruit juices and tea drinks by high-performance liquid chromatography. A varieties of environmental hydrophobic deep eutectic solvents serving as extraction agents were prepared using L-menthol and decanoic acid as hydrogen-bond acceptor and hydrogen-bond donor, respectively. The deep eutectic solvents were ultrasonically dispersed in sample solutions, solidified in a freezer and easily harvested. The main variables were optimized by one-factor-at-a-time and response surface test. The new method performs well with relative recovery of 71.75-109.40%, linear range of 2.5-5000 µg/L (r ≥ 0.9968), detection limit of 0.75-8.45 µg/L, quantification limit of 2.5-25 µg/L,, and inter- and intraday relative standard deviations below 13.53 and 14.84%, respectively. As for the extraction mechanism, deep eutectic solvents were disposed into many fine particles in the solution and captured the analytes based on the changes of particle size and quantity in deep eutectic solvents droplets after extraction. The environmental method can successfully detect fungicide residues in real fruit juices and tea drinks.

Phase-Transition Thermal Charging of a Channel-Shape Thermal Energy Storage Unit: Taguchi Optimization Approach and Copper Foam Inserts.

Thermal energy storage is a technique that has the potential to contribute to future energy grids to reduce fluctuations in supply from renewable energy sources. The principle of energy storage is to drive an endothermic phase change when excess energy is available and to allow the phase change to reverse and release heat when energy demand exceeds supply. Unwanted charge leakage and low heat transfer rates can limit the effectiveness of the units, but both of these problems can be mitigated by incorporating a metal foam into the design of the storage unit. This study demonstrates the benefits of adding copper foam into a thermal energy storage unit based on capric acid enhanced by copper nanoparticles. The volume fraction of nanoparticles and the location and porosity of the foam were optimized using the Taguchi approach to minimize the charge leakage expected from simulations. Placing the foam layer at the bottom of the unit with the maximum possible height and minimum porosity led to the lowest charge time. The optimum concentration of nanoparticles was found to be 4 vol.%, while the maximu possible concentration was 6 vol.%. The use of an optimized design of the enclosure and the optimum fraction of nanoparticles led to a predicted charging time for the unit that was approximately 58% shorter than that of the worst design. A sensitivity analysis shows that the height of the foam layer and its porosity are the dominant variables, and the location of the porous layer and volume fraction of nanoparticles are of secondary importance. Therefore, a well-designed location and size of a metal foam layer could be used to improve the charging speed of thermal energy storage units significantly. In such designs, the porosity and the placement-location of the foam should be considered more strongly than other factors.

Formulation of Ocular In Situ Gels with Lithuanian Royal Jelly and Their Biopharmaceutical Evaluation In Vitro.

Royal jelly is a natural substance produced by worker bees that possesses a variety of biological activities, including antioxidant, anti-inflammatory, antibacterial, and protective. Although fresh royal jelly is kept at low temperatures, to increase its stability, it needs to be incorporated into pharmaceutical formulations, such as in situ gels. The aim of this study was to formulate in situ ocular gels containing Lithuanian royal jelly for topical corneal use in order to increase the retention time of the formulation on the ocular surface and bioavailability. Gels were evaluated for physicochemical characteristics (pH, rheological properties, refractive index) and in vitro drug release measuring the amount of 10-hydroxy-2-decenoic acid (10-HDA). An ocular irritation test and cell viability tests were performed using the SIRC (Statens Seruminstitut Rabbit Cornea) cell culture line. Results indicated that all the in situ gels were within an acceptable pH and refractive index range close to corneal properties. Rheology studies have shown that the gelation temperature varies between 25 and 32 °C, depending on the amount of poloxamers. The release studies have shown that the release of 10-HDA from in situ gels is more sustained than royal jelly suspension. All gel formulations were non-irritant according to the short-time exposure test (STE) using the SIRC cell culture line, and long-term cell viability studies indicated that the formulations used in small concentrations did not induce cell death. Prepared in situ gels containing royal jelly have potential for ocular drug delivery, and they may improve the bioavailability, stability of royal jelly, and formation of non-irritant ocular formulations.

Prebiotic Peptide Synthesis and Spontaneous Amyloid Formation Inside a Proto-Cellular Compartment.

Cellular life requires a high degree of molecular complexity and self-organization, some of which must have originated in a prebiotic context. Here, we demonstrate how both of these features can emerge in a plausibly prebiotic system. We found that chemical gradients in simple mixtures of activated amino acids and fatty acids can lead to the formation of amyloid-like peptide fibrils that are localized inside of a proto-cellular compartment. In this process, the fatty acid or lipid vesicles act both as a filter, allowing the selective passage of activated amino acids, and as a barrier, blocking the diffusion of the amyloidogenic peptides that form spontaneously inside the vesicles. This synergy between two distinct building blocks of life induces a significant increase in molecular complexity and spatial order thereby providing a route for the early molecular evolution that could give rise to a living cell.

A Step toward Molecular Evolution of RNA: Ribose Binds to Prebiotic Fatty Acid Membranes, and Nucleosides Bind Better than Individual Bases Do.

A major challenge in understanding how biological cells arose on the early Earth is explaining how RNA and membranes originally colocalized. We propose that the building blocks of RNA (nucleobases and ribose) bound to self-assembled prebiotic membranes. We have previously demonstrated that the bases bind to membranes composed of a prebiotic fatty acid, but evidence for the binding of sugars has remained a technical challenge. Here, we used pulsed-field gradient NMR spectroscopy to demonstrate that ribose and other sugars bind to membranes of decanoic acid. Moreover, the binding of some bases is strongly enhanced when they are linked to ribose to form a nucleoside or - with the addition of phosphate - a nucleotide. This enhanced binding could have played a role in the molecular evolution leading to the production of RNA.

Ionophore-based pH independent detection of ions utilizing aggregation-induced effects.

Ionophores have been integrated into various electrochemical and optical sensing platforms for the selective detection of ions. Previous ionophore-based optical sensors rely on a H+ chromoionophore as the signal transducer and consequently, suffered from a pH cross-response. pH independent methods were proposed very recently by utilizing the solvatochromic dyes or the exhaustive mode. Here, we report a pH independent sensing principle based on nanospheres containing ionophores. As the ion-exchange occurs, the signal transducer undergoes aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ), leading to a dramatic change in fluorescence intensity. The principle was evaluated on different ionophores including those selective for K+, Na+, Ca2+, and Pb2+. The nanospheres were also introduced into microfluidic chips and successfully applied for the determination of sodium and potassium ion concentrations in diluted blood serum and urine samples.

Development of organic solvents-free mode of solidification of floating organic droplet-based dispersive liquid-liquid microextraction for the extraction of polycyclic aromatic hydrocarbons from honey samples before their determination by gas chromatography-mass spectrometry.

In this study, a green mode of solidification of floating organic droplet-based dispersive liquid-liquid microextraction has been developed for the extraction of 16 polycyclic aromatic hydrocarbons from honey samples before their determination by gas chromatography-mass spectrometry. In this method, an appropriate volume of menthol:decanoic acid deep eutectic solvent (as an extraction solvent) is added on a sugar cube (as a disperser agent). In the following, the cube is released into the diluted honey sample placed in a tube. After manual shaking a cloudy state is obtained as a result of dispersing the extraction solvent droplets throughout the sample solution and the analytes are extracted into them. After placing the tube in an ice bath, the droplet of the extractant is solidified on the top of the solution. This drop is taken and after dissolving in acetonitrile, an aliquot of the solution is injected into the separation system. Under optimum conditions, the suggested approach had high extraction recoveries (76-93%) and enrichment factors (380-465), low limits of detection (14-52 ng/kg) and quantification (47-173 ng/kg), and satisfactory repeatability (relative standard deviation ≤ 9%).

A modified quick, easy, cheap, effective, rugged, and safe method with hydrophobic natural deep eutectic solvent as extractant and analyte protectant for analyzing pyrethroid residues in tomatoes.

In this work, a novel quick, easy, cheap, effective, rugged, and safe technique with hydrophobic natural deep eutectic solvent as both extractant and analyte protectant was developed and combined with gas chromatography-tandem mass spectrometry to analyze pyrethroid residues in tomatoes. Eight hydrophobic natural deep eutectic solvents were first evaluated as analyte protectants and those with decanoic acid or lactic acid as hydrogen bond donor were demonstrated to be effective in compensating for the matrix effects of pyrethroids in the gas chromatography system. Hence, they were added to solvent standards for correcting the quantitation errors instead of matrix-matched calibration standards. Then the abilities of these acid-based deep eutectic solvents to extract pyrethriods from tomatoes were evaluated. Results showed the recoveries of all pyrethroids reached to over 80% with only 5 mL menthol:decanoic acid (1:1) used, and good phase separation was easily achieved without the addition of inorganic salt in the extraction step, indicating hydrophobic natural deep eutectic solvent could be a green substitute for acetonitrile in the quick, easy, cheap, effective, rugged, and safe extraction. Compared with the conventional method, the proposed protocol improved the recoveries, reduced the matrix effects, and simplified the extraction step, demonstrating to be an effective, fast, and green method.

Hydrophobic deep eutectic solvent as a green extractant for high-performance liquid chromatographic determination of tetracyclines in water samples.

A green extractant, hydrophobic deep eutectic solvent was first introduced for extraction of tetracycline, oxytetracycline, and chlortetracycline from environmental water samples prior to high-performance liquid chromatography determination. Deep eutectic solvents consist of methyltrioctylammonium chloride and various medium-chain alcohols/acids, and are easy in preparation, low cost and toxicity, desirably biodegradable, and biocompatible. The overall time required for sample preparation was 6 min and the volume of organic solvent used for extraction was only 400 µL. Under the optimized extraction condition, the present method yielded low limit of detection (0.5-2.0 ng/mL), acceptable precision (relative standard deviations < 9.7%), good linearity from 2.0 to 500 ng/mL (r2  ≥ 0.9991). This optimized procedure was applied for determination of tetracyclines in different water samples with desirable spiked recovery ranged from 77.5 to 87.6%. There is, therefore, a great potential to further expand application of the method for investigation of other ultra-trace analyte(s) in environmental matrixes.

Analytical Methodology for Trace Determination of Propoxur and Fenitrothion Pesticide Residues by Decanoic Acid Modified Magnetic Nanoparticles.

A sensitive, rapid, reliable, and easily applicable method based on magnetic solid phase extraction (MSPE) combined with HPLC-PDA was developed for monitoring propoxur (PRO) and fenitrothion (FEN) pesticides in environmental water samples. The effect of major experimental variables on the extraction efficiency of both the pesticides was investigated and optimized systematically. For this purpose, a new magnetic material containing decanoic acid on the surface of particles was synthesized and characterized by XRD, FT-IR, SEM, EDX, and TGA analysis in detail. The simultaneous determination of pesticide molecules was carried out by using a Luna Omega C18 column, isocratic elution of acetonitrile (ACN): Water (70:30 v/v) with a flow rate of 1.2 mL min-1. After MSPE, the linear range for pesticide molecules (r2 > 0.9982) was obtained in the range of 5-800 and 10-800 ng mL-1, respectively. The limit of detections (LOD) are 1.43 and 4.71 ng mL-1 for PRO and FEN, respectively while RSDs % are below 3.5%. The applicability of the proposed method in four different environmental samples were also investigated using a standard addition-recovery procedure. Average recoveries at two spiking levels were over the range of 91.3-102.5% with RSD < 5.0% (n = 3). The obtained results show that decanoic acid grafted magnetic particles in MSPE combined with HPLC-PDA is a fast and simple method for the determination of PRO and FEN in environmental water samples.

New Hydroxydecanoic Acid Derivatives Produced by an Dndophytic Yeast Aureobasidium pullulans AJF1 from Flowers of Aconitum carmichaeli.

Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1-3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1-3) were established using modified Mosher's method together with analysis of NMR data for their acetonide derivatives. All the isolates (1-3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.

Overproduction of MCL-PHA with high 3-hydroxydecanoate Content.

Methods of producing medium-chain-length poly-3-hydroxyalkanoate (mcl-PHA) with high content of the dominant subunit, 3-hydroxydecanoate (HD), were examined with an emphasis on a high yield of polymer from decanoic acid. High HD content was achieved by using a ß-oxidation knockout mutant of Pseudomonas putida KT2440 (designated as P. putida DBA-F1) or by inhibiting ß-oxidation with addition of acrylic acid (Aa) to wild type P. putida KT2440 in carbon-limited, fed-batch fermentations. At a substrate feed ratio of decanoic acid and acetic acid to glucose (DAA:G) of 6:4 g/g, P. putida DBA-F1 accumulated significantly higher HD (97 mol%), but much lower biomass (8.5 g/L) and PHA (42% of dry biomass) than the wild type. Both biomass and PHA concentrations were improved by decreasing the ratio of DAA:G to 4:6. Moreover, when the substrate feed ratio was further decreased to 2:8, 18 g/L biomass containing 59% mcl-PHA consisting of 100 mol% HD was achieved. The yield of PHA from decanoic acid was 1.24 (g/g) indicating that de novo synthesis had contributed to production. Yeast extract and tryptone (YET) addition allowed the mutant strain to accumulate 74% mcl-PHA by weight with 97 mol% HD at a production rate of 0.41 g/L/hr, at least twice that of published data for any ß-oxidation knock-out mutant. Higher biomass concentration was achieved with Aa inhibition of ß-oxidation in the wild type but the HD content (84 mol%) was less than that of the mutant. A carbon balance showed a marked increase in supernantant organic carbon for the mutant indicating overflow metabolism. Increasing the dominant monomer content (HD) greatly increased melting point, crystallinity, and rate of crystallization.

Tunability of Biodegradable Poly(amine- co-ester) Polymers for Customized Nucleic Acid Delivery and Other Biomedical Applications.

Gene therapy promises to treat diseases that arise from genetic abnormalities by correcting the underlying cause of the disease rather than treating the associated symptoms. Successful transfer of nucleic acids into cells requires efficient delivery vehicles that protect the cargo and can penetrate the appropriate cellular barriers before releasing their contents. Many viral vectors and synthetic polycationic vectors for nucleic acid delivery do not translate well from in vitro to in vivo applications due to their instability and toxicity. We synthesized and characterized a library of biocompatible low charge density polymers from a family of poly(amine- co-ester) (PACE) terpolymers produced via enzyme catalyzed polymerization. PACE polymers are highly customizable; we found that the terpolymer composition can be optimized to produce efficient transfection of various nucleic acids-including DNA plasmids, mRNA, and siRNA-in specific cell types with low toxicity. Our findings suggest that the unique tunability of PACEs offers new tools for gene therapy and other biomedical applications.

Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells.

Wide application of perfluoroalkyl acids (PFAAs) has raised great concerns on their side-effects on human health. PFAAs have been shown to accumulate mainly in the liver and cause hepatotoxicity. However, PFAAs can also deposit in lung tissues through air-borne particles and cause serious pulmonary toxicity. But the underlying mechanisms are still largely unknown. Autophagy is a type of programmed cell death parallel to necrosis and apoptosis, and may be involved in the lung toxicity of PFAAs. In this study, lung cancer cells, A549, were employed as the model to investigate the effects of three PFAAs with different carbon chain lengths on cell autophagy. Through Western blot analysis on LC3-I/II ratio of cells exposed to non-cytotoxic concentration (200 µM) and cytotoxic concentration (350 µM), we found concentration-dependent increase of autophagosomes in cells, which was further confirmed by TEM examination on ultra-thin section of cells and fluorescence imaging on autophagosomes in live cells. The abundance of p62 increased with the PFAAs concentration indicating the blockage of autophagy flux. Furthermore, we identified the mitochondrial autophagy (mitophagy) and endoplasmic reticulum autophagy (ER-phagy) morphologically as the major types of autophagy, suggesting the disruption on mitochondria and ERs. These organelle damages were confirmed by the overgeneration of ROS, hyperpolarization of mitochondrial membrane potential, as well as the up-regulation of ER-stress-related proteins, ATF4 and p-IRE1. Further analysis on the signaling pathways showed that PFAAs activated the MAPK pathways and inhibited the PI3K/Akt pathway, with potencies following the order of PFDA > PFNA > PFOA. Anti-oxidant (NAC) treatment did not rescue cells from death, indicating that oxidative stress is not the reason of cytotoxicity. Inhibition of autophagy by Atg5 siRNA and chloroquine even increased the toxicity of PFAAs, suggesting that PFAAs-autophagy was induced as the secondary effects of organelle damages and played a protective role during cell death.

The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry.

OleT is a cytochrome P450 enzyme that catalyzes the removal of carbon dioxide from variable chain length fatty acids to form 1-alkenes. In this work, we examine the binding and metabolic profile of OleT with shorter chain length (n ≤ 12) fatty acids that can form liquid transportation fuels. Transient kinetics and product analyses confirm that OleT capably activates hydrogen peroxide with shorter substrates to form the high-valent intermediate Compound I and largely performs C-C bond scission. However, the enzyme also produces fatty alcohol side products using the high-valent iron oxo chemistry commonly associated with insertion of oxygen into hydrocarbons. When presented with a short chain fatty acid that can initiate the formation of Compound I, OleT oxidizes the diagnostic probe molecules norcarane and methylcyclopropane in a manner that is reminiscent of reactions of many CYP hydroxylases with radical clock substrates. These data are consistent with a decarboxylation mechanism in which Compound I abstracts a substrate hydrogen atom in the initial step. Positioning of the incipient substrate radical is a crucial element in controlling the efficiency of activated OH rebound.

Correlating Membrane Morphological Responses with Micellar Aggregation Behavior of Capric Acid and Monocaprin.

The interaction of single-chain lipid amphiphiles with phospholipid membranes is relevant to many scientific fields, including molecular evolution, medicine, and biofuels. Two widely studied compounds within this class are the medium-chain saturated fatty acid, capric acid, and its monoglyceride derivative, monocaprin. To date, most studies about these compounds have involved in vitro evaluation of their biological activities, while mechanistic details of how capric acid and monocaprin interact with phospholipid bilayers remain elusive. Herein, we investigated the effect of these two compounds on the morphological and fluidic properties of prefabricated, supported lipid bilayers (SLBs). The critical micelle concentration (CMC) of each compound was determined by fluorescence spectroscopy measurements. At or above its CMC, capric acid induced the formation of elongated tubules protruding from the SLB, as determined by quartz crystal microbalance-dissipation and fluorescence microscopy experiments. By contrast, monocaprin induced the formation of elongated tubules or membrane buds below and above its CMC, respectively. Fluorescence recovery after photobleaching (FRAP) experiments indicated that capric acid increased bilayer fluidity only above its CMC, whereas monocaprin increased bilayer fluidity both above and below its CMC. We discuss these findings in the context of the two compounds' structural properties, including net charge, molecular length and hydrogen-bonding capacity. Collectively, the findings demonstrate that capric acid and monocaprin differentially affect the morphological and fluidic properties of SLBs, and that the aggregation state of the compounds plays a critical role in modulating their interactions with phospholipid membranes.