Temperature-modulated Differential Scanning Calorimetry Research Articles

Molecular Dynamics and Self-Assembly in Double Hydrophilic Block and Random Copolymers.

We investigate the self-assembly and dynamics of double hydrophilic block copolymers (DHBCs) composed of densely grafted poly[oligo(ethylene glycol) methacrylate] (POEGMA) and poly(vinyl benzyl trimethylammonium chloride) (PVBTMAC) parent blocks by means of calorimetry, small- and wide-angle X-ray scattering (SAXS/WAXS), and dielectric spectroscopy. A weak segregation strength is evident from X-ray measurements, implying a disordered state and reflecting the inherent miscibility between the host homopolymers. The presence of intermixed POEGMA/PVBTMAC nanodomains results in homogeneous molecular dynamics, as evidenced through isothermal dielectric and temperature-modulated DSC measurements. The intermixed process undergoes a glass transition at a temperature approximately 40 K higher than the vitrification of bulk POEGMA segments, and it shifts to an even higher temperature by increasing the content of the hard block. At temperatures below the intermixed glass transition temperature, the confined POEGMA segments between the glassy intermixed regions contribute to a segmental process featuring (i) reduced glass transition temperature (Tg), (ii) reduced dielectric strength, (iii) broader distribution of relaxation times, and (iv) reduced fragility compared to the POEGMA homopolymer. We also observe two glass transition temperatures of dry PVBTMAC, which we attribute to the backbone and side chain segmental relaxation. To the best of our knowledge, this is the first time in the literature that these glass transitions of dry PVBTMAC have been reported. Finally, this study shows that excellent mixing of the two homopolymers is obtained, and this implies that different properties of this copolymer system can be tailored by adjusting the concentration of each homopolymer.

Temperature dependence of structural evolution and fragility of glass-forming monohydroxy alcohols

The dynamic, structural, and thermodynamic properties of thirty-four monohydroxy alcohols with varying molecular architectures, including differences in alkyl chain length, OH group position, and presence/type of carbon ring, were investigated. Results of dielectric spectroscopy, temperature-modulated differential scanning calorimetry, and X-ray diffraction, were analyzed to verify correlations between the glass transition temperature (Tg), molar mass (M), boiling temperature (Tb), dynamic and thermodynamic fragility (mα and m), and the structurally related parameter (S). The collected data revealed that primary and secondary alcohols generally adhere to the correlations Tg ∝ M0.51 and Tb = 132 + 2.2Tg, while alcohols with phenyl ring deviate from these trends. Moreover, it was found that the changes in the width of the main diffraction peak normalized by the peak position ΔQM/QM over temperature scaled by Tg correspond to the variable m. However, the extent and course of this relationship varies across alcohols belonging to different structural groups. The weakest correlation and largest scatter between S and m occur for phenyl alcohols exhibiting the greatest structural heterogeneity. This study underscores the challenges of establishing universal correlations between physical variables within the diverse group of monohydroxy alcohols and emphasizes the importance of considering specific molecular features in predicting glass-forming behaviour.

Critical Cooling Rate of Fast-Crystallizing Polyesters: The Example of Poly(alkylene trans-1,4-cyclohexanedicarboxylate)

Controlling the cooling rate experienced by a material during a manufacturing process is a challenge and a major issue. Industrial processing techniques are very diverse and may involve a whole range of cooling rates, which are sometimes extremely high for small and/or thin manufactured parts. For polymers, the cooling rate has consequences on both the microstructure and the time-dependent properties. The common cooling rates associated with conventional calorimetric measurements are generally limited to a few tens of degrees per minute. This work combines several calorimetric techniques (DSC, modulated-temperature DSC, stochastically-modulated DSC and Fast Scanning Calorimetry) to estimate the critical cooling rate required to melt-quench fast-crystallizing polyesters to their fully amorphous state, based on the example of a series of poly(alkylene trans-1,4-cyclohexanedicarboxylate) (PCHs) with a number of methylene groups in the main structure of the repeating unit nCH2 varying from 3 to 6. The even-numbered ones require faster cooling rates (about 3000 K s−1 for nCH2 = 4, between 500 and 1000 K s−1 for nCH2 = 6) compared to the odd-numbered ones (between 50 K min−1 and 100 K s−1 for nCH2 = 3, between 10 and 30 K min−1 for nCH2 = 5).

Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential

Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1–––3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.

The effect of skin diffusion kinetics of isopropyl ester permeation enhancers on drug permeation: Role of lateral spread and penetration characteristics

The purpose of present work was to study the effects of permeation enhancers’ two kinetic behaviors of simultaneous lateral diffusion and vertical penetration in the skin on its enhancing effect. The skin diffusion kinetics of isopropyl ester permeation enhancers were characterized by the innovative concentric tape peeling study and Raman imaging, which were quantitatively assessed through innovative parameters, namely, lateral-to-vertical penetration amount (CL-V) and lateral-to-vertical penetration distance (DL-V). The enhancement effect of permeation enhancers on drug flurbiprofen (FLU) was assessed by in vitro skin permeation tests, which were confirmed by transdermal water loss and skin resistance study. The relationship between kinetic parameters of permeation enhancers and permeation parameters of FLU was carried out by correlation analysis. The molecular mechanisms of effect of skin diffusion kinetics of permeation enhancers on drug permeation were characterized by molecular docking, modulated-temperature differential scanning calorimetry (MTDSC), Raman spectra, solid-state NMR and molecular dynamic simulation. The results indicated skin diffusion kinetics of short-chain (C8–C12) isopropyl ester permeation enhancers were governed by vertical penetration, while long-chain (C14–C18) ones were characterized by lateral spread. Quadratic correlation between CL-V and enhancement ratio of permeation-retention ratio of FLU (ERQ/R) (R2 = 0.95), DL-V and enhancement ratio of permeation area (ERA) of FLU (R2 = 0.98) indicating that varied skin diffusion kinetics of permeation enhancers directly influenced the barrier function of stratum corneum (SC) and further enhancing drug permeation. In terms of molecular mechanism, long-chain isopropyl ester enhancers had good miscibility with SC, leading to their high CL-V and DL-V, and causing strong interaction strength with SC and resulting in weaker skin barrier function for drug permeation. In summary, in comparison to short-chain isopropyl ester enhancers that relied on penetration, long-chain ones that depended on lateral spread exhibited greater enhancement efficacy, which guided the application of enhancers in transdermal formulations.

Modification of poly(lactate) via polymer blending with microbially produced poly[(R)-lactate-co-(R)-3-hydroxybutyrate] copolymers

This study investigated the effect of polymer blending of microbially produced poly[(R)-lactate-co-(R)-3-hydroxybutyrate] copolymers (LAHB) with poly(lactate) (PLA) on their mechanical, thermal, and biodegradable properties. Blending of high lactate (LA) content and high molecular weight LAHB significantly improved the tensile elongation of PLA up to more than 250 % at optimal LAHB composition of 20–30 wt%. Temperature-modulated differential scanning calorimetry and dynamic mechanical analysis revealed that PLA and LAHB were immiscible but interacted with each other, as indicated by the mutual plasticization effect. Detailed morphological characterization using scanning probe microscopy, small-angle X-ray scattering, and solid-state NMR confirmed that PLA and LAHB formed a two-phase structure with a characteristic length scale as small as 20 nm. Because of mixing in this order, the polymer blends were optically transparent. The biological oxygen demand test of the polymer blends in seawater indicated an enhancement of PLA biodegradation during biodegradation of the polymer blends.

Fragility and Tendency to Crystallization for Structurally Related Compounds.

The present study was designed to investigate the physical stability of three organic materials with similar chemical structures. The examined compounds revealed completely different crystallization tendencies in their supercooled liquid states and were classified into three distinct classes based on their tendency to crystallize. (S)-4-Benzyl-2-oxazolidinone easily crystallizes during cooling from the melt; (S)-4-Benzylthiazolidine-2-thione does not crystallize during cooling from the melt, but crystallizes easily during subsequent reheating above Tg; and (S)-4-Benzyloxazolidine-2-thione does not crystallize either during cooling from the melt or during reheating. Such different tendencies to crystallize are observed despite the very similar chemical structures of the compounds, which only differ in oxide or sulfur atoms in one of their rings. We also studied the isothermal crystallization kinetics of the materials that were shown to transform into a crystalline state. Molecular dynamics and thermal properties were thoroughly investigated using broadband dielectric spectroscopy, as well as conventional and temperature-modulated differential scanning calorimetry in the wide temperature range. It was found that all three glass formers have the same dynamic fragility (m = 93), calculated directly from dielectric structural relaxation times. This result verifies that dynamic fragility is not related to the tendency to crystallize. In addition, thermodynamic fragility predictions were also made using calorimetric data. It was found that the thermodynamic fragility evaluated based on the width of the glass transition, observed in the temperature dependence of heat capacity, correlates best with the tendency to crystallize.

Ion transport, mechanical properties and relaxation dynamics in structural battery electrolytes consisting of an imidazolium protic ionic liquid confined into a methacrylate polymer

The effect of confining a liquid electrolyte into a polymer matrix was studied by means of Raman spectroscopy, differential scanning calorimetry, temperature-modulated differential scanning calorimetry, dielectric spectroscopy, and rheology. The polymer matrix was obtained from thermal curing ethoxylated bisphenol A dimethacrylate while the liquid electrolyte consisted of a protic ionic liquid based on the ethyl-imidazolium cation [C2HIm] and the bis(trifluoromethanesulfonyl)imide [TFSI] anion, doped with LiTFSI salt. We report that the confined liquid phase exhibits the following characteristics: (i) a distinctly reduced degree of crystallinity; (ii) a broader distribution of relaxation times; (iii) reduced dielectric strength; (iv) a reduced cooperativity length scale at the liquid-to-glass transition temperature (T g); and (v) up-speeded local T g-related ion dynamics. The latter is indicative of weak interfacial interactions between the two nanophases and a strong geometrical confinement effect, which dictates both the ion dynamics and the coupled structural relaxation, hence lowering Tg by about 4 K. We also find that at room temperature, the ionic conductivity of the structural electrolyte achieves a value of 0.13 mS/cm, one decade lower than the corresponding bulk electrolyte. Three mobile ions (Im+, TFSI-, and Li+) contribute to the measured ionic conductivity, implicitly reducing the Li+ transference number. In addition, we report that the investigated solid polymer electrolytes exhibit the shear modulus needed for transferring the mechanical load to the carbon fibers in a structural battery. Based on these findings, we conclude that optimized microphase-separated polymer electrolytes, including a protic ionic liquid, are promising for the development of novel multifunctional electrolytes for use in future structural batteries.

Carbon Dots-Biomembrane Interactions and Their Implications for Cellular Drug Delivery.

The effect of carbon dots (CDs) on a model blayer membrane was studied as a means of comprehending their ability to affect cell membranes. Initially, the interaction of N-doped carbon dots with a biophysical liposomal cell membrane model was investigated by dynamic light scattering, z-potential, temperature-modulated differential scanning calorimetry, and membrane permeability. CDs with a slightly positive charge interacted with the surface of the negative-charged liposomes and evidence indicated that the association of CDs with the membrane affects the structural and thermodynamic properties of the bilayer; most importantly, it enhances the bilayer's permeability against doxorubicin, a well-known anticancer drug. The results, like those of similar studies that surveyed the interaction of proteins with lipid membranes, suggest that carbon dots are partially embedded in the bilayer. In vitro experiments employing breast cancer cell lines and human healthy dermal cells corroborated the findings, as it was shown that the presence of CDs in the culture medium selectively enhanced cell internalization of doxorubicin and, subsequently, increased its cytotoxicity, acting as a drug sensitizer.

Rationalizing the interfacial layer in polymer nanocomposites: Correlation between enthalpy and dielectric relaxation

The accurate and convenient characterization of the interfacial layer is a crucial prerequisite for understanding the relationship between structure and macroscopic properties in polymer nanocomposites (PNCs). Herein, enthalpy relaxation and interfacial layer properties estimated from temperature-modulated differential scanning calorimetry (TMDSC) and broadband dielectric spectroscopy (BDS) of model PNCs with attractive interactions are investigated. We demonstrate that enthalpy relaxation enables the accurate quantification of the volume fraction of the interfacial layer (φint) as TMDSC and BDS. The parameter (χint) corresponding to the decreased degree of enthalpy hysteresis (ΔHR) related to the contribution of the interfacial layer, is identical with φint estimated from BDS, while presents only similar dependence on nanoparticle loading with φint estimated from TMDSC. This interesting phenomenon can be ascribed to the consistency between enthalpy and dielectric relaxation, which both characterize the dynamic change of polymer mainly originating from segmental relaxation. Such an unexpected correlation between enthalpy and dielectric relaxation provides a new approach to characterize the interfacial layer properties of PNCs and understand its impact on the glass transition behavior.

Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability

There is a great interest to develop co-amorphous drug delivery systems to enhance the solubility of biopharmaceutics classification system (BCS) class II and IV drugs. However, most reported systems only resulted in severalfold solubility improvement. Tranilast (TRA) is an anti-allergic drug used to treat bronchial asthma and allergic rhinitis. It is a BCS class II drug and its poor aqueous solubility affects its absorption in vivo. To address this issue, a natural alkaloid matrine (MAR) with interesting biological activities was chosen to form a co-amorphous system with TRA, based on the solubility parameter and phase solubility experiment. The TRA-MAR drug-drug co-amorphous system was prepared by the solvent evaporation method, and further characterized by powder X-ray diffraction and modulated temperature differential scanning calorimetry. Fourier transform infrared spectroscopy, FT-Raman, and X-ray photoelectron spectroscopy revealed the formation of salt and the presence of strong intermolecular interactions in the TRA-MAR co-amorphous system, which are also supported by molecular dynamics simulations, showing ionic and hydrogen bonding interactions. This co-amorphous system exhibited excellent physical stability at both 25 °C and 40 °C under anhydrous silica gel condition. Finally, co-amorphous TRA-MAR showed greatly enhanced solubility (greater than 100-fold) and rapid release behavior in the vitro release experiments. NMR spectroscopy revealed the strong intermolecular interactions between TRA and MAR in both DMSO‑d6 and D2O. Our study resulted in a TRA-MAR co-amorphous drug system with significant solubility improvement and showcased the great potential to improve the dissolution behaviors of BCS class II and IV drugs through the co-amorphization approach.

A skin pharmacokinetics study of permeation enhancers: The root cause of dynamic enhancement effect on in vivo drug permeation

Skin pharmacokinetics (SPK) of permeation enhancers can answer the question of why enhancement effects different at the kinetic level. Herein, SPK of permeation enhancers were classified into two categories, namely, lateral elimination (elimination to surrounding stratum corneum (SC)) and longitudinal elimination (elimination to deep epidermal (EP)). They were evaluated with a specific parameter for permeation enhancers, diffusion ratio (DRSC-EP), according to results of tissue-distribution test, molecular dynamic (MD) simulation, and confocal laser scanning microscopy (CLSM). The linear relationship between ke-enahcer and Δ Cmax-drug (R2 = 0.92), MRTenhancer and Δ Tmax-drug (R2 = 0.97), AUCt-enhancer and Δ AUCt-drug (R2 = 0.90) suggesting that SPK of permeation enhancers precisely controlled dynamic process of drug permeation in vivo. The molecular mechanisms of the dynamic effect of SPK process on drug transdermal behaviors were characterized by modulated-temperature differential scanning calorimetry (MTDSC), dielectric spectroscopy, small-angle X-ray scattering (SAXS), solid-state NMR. Permeation enhancers with high molecular weight (M.W.) and high polar surface area (P.S.A.) had good compatibility and strong interaction strength with SC, leading their lateral-elimination behavior, causing their low DRSC-EP and resulting in low ke-enhancer, long MRTenhancer, and large AUCt-enhancer. Consequently, skin barrier can be rapidly opened fast and to a great extent. In summary, compared with SPK of permeation enhancers with longitudinal elimination, SPK of permeation enhancers with lateral elimination can enable more sustainable and greater drug permeation. The information about SPK of permeation enhancers offered a criterion to estimate its permeation-enhancement effect on the drug and its subsequent application in transdermal formulations.

Cross-Linking Mechanisms of a Rigid Plant Oil-Based Thermoset from Furfural-Derived Cyclobutane

cis-Cyclobutane-1,2-dicarbocylic acid (CBDA-2) was synthesized and used as a biobased hardener to cross-link epoxidized linseed oil to produce a fully biobased thermoset. The polymerization mechanism was studied by means of real-time attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), stochastically modulated temperature DSC, and rheometry. The study highlights the importance of hydrogen bonding of CBDA-2 and catalytic effect of hydroxyl groups created during the reaction. Evolution of reactive functions with temperature and time, variation of activation energy, and pre-exponential factor was correlated to macroscopic changes, such as heat capacity variations and chemorheology. A macrokinetic model was proposed to describe the complete polymerization mechanism. It is shown that the obtained parameters accurately describe the polymerization using parameters with a real physical meaning.

Calculation of the degree of crystallinity of HDPE/GNPs nanocomposites by using various experimental techniques: a comparative study

This work is a comparative study of four different techniques to determine the crystallinity of high-density polyethylene (HDPE) nanocomposites filled with different diameter sizes (5, 15 and 25 μm) of graphene nanoplatelets (GNPs) at various amounts (0.5–5 wt%). The structure of HDPE/GNPs nanocomposites was extensively studied by using different experimental methods, such as X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. To further provide a complete comparison, differential scanning calorimetry measurements were utilized to calculate the crystallinity values, while temperature-modulated DSC was employed to investigate the possible mechanism of the different crystalline structures. It was found that these methods can be used to estimate the crystallinity, but the sample parameters and experimental conditions must be taken into consideration. All the techniques showed that the crystallinity depends on GNPs size and content. The distance between dispersed platelets was substantial at low concentrations of GNPs, making it comparatively easy for additional nucleation sites to incorporate the polymer matrix, and the crystal nucleus was simply formed. However, at high concentrations of GNPs, the diffusion of polymer chains to the growing crystallites was hindered by large GNPs particles, despite the formation of additional nucleation sites.

Mechanistic insights of different release behaviors dominated by drug physicochemical properties in polyisobutylene pressure sensitive adhesive

The purpose of this study was to investigate the effect of the physicochemical parameters of drugs on their own release behaviors in polyisobutylene pressure sensitive adhesive (PIB PSA), which provided a theoretical guidance for the application of PIB in transdermal drug delivery system (TDDS). Seven drugs with different physicochemical parameters including clonidine (CLO), flurbiprofen (FLU), diclofenac (DIC), ibuprofen (IBU), zolmitriptan (ZOL), lidocaine (LID), tulobuterol (TUL) and the mixed adhesive (7:3, w/w) of Oppanol® B 15 N (M.W. = 108,000 Da) and Oppanol® N 50 (M.W. = 565,000 Da) were selected for in vitro drug release and skin permeation studies. Regression analysis was used to study the relationship between physicochemical parameters and release behaviors. The release behaviors of drugs were a negative correlation with polarizability and dipole moment per molecular volume (μ/V), which represented van der Waals and dipole–dipole interaction, respectively. Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MDSC) and molecular dynamics simulation were used to provide molecular details of the interaction between the drug and PIB. The free volume and molecular mobility of PIB were characterized using mechanical property tests, rheology study, MDSC and molecular dynamics simulation. Based on the above results, drugs with high polarizability and μ/V had stronger van der Waals and dipole–dipole interaction with PIB, reducing the free volume and molecular mobility of PIB, so that the drug struggled to release from PIB. In addition, the diffusion activation energy of the drug was calculated by using the variable temperature release study to characterize the ease of drug release from the kinetic aspect. And the trends of in vitro drug release and skin penetration profiles were basically similar. Thus, it was thought that the physicochemical parameters of the drug played a vital role in the drug release behavior of PIB PSAs and would affect the skin penetration process, which provided a reference for the design and application of patches based on PIB PSAs in TDDS.

Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior.

There is strong interest to develop affordable treatments for the infection-associated rheumatoid arthritis (RA). Here, we present a drug-drug co-amorphous strategy against RA and the associated bacterial infection by the preparation and characterization of two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF), two potent antibiotics. Both of them were comprehensively characterized using powder X-ray diffraction, temperature-modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The co-amorphous forms of SIN-PTM and SIN-SULF exhibited high Tgs at 139.10 ± 1.0 and 153.3 ± 0.2 °C, respectively. After 6 months of accelerated tests and 1 month of drug-excipient compatibility experiments, two co-amorphous systems displayed satisfactory physical stability. The formation of salt and strong intermolecular interactions between SIN and PTM or SULF, as well as the decreased molecular mobility in co-amorphous systems, may be the intrinsic mechanisms underlying the excellent physical stability of both co-amorphous systems. In dissolution tests, two co-amorphous systems displayed distinct reduced SIN-accumulative releases (below 20% after 6 h of release experiments), which may lead to its poor therapeutic effect. Hence, we demonstrated a controlled release strategy for SIN by the addition of a small percentage of polymers and a small-molecule surfactant to these two co-amorphous samples as convenient drug excipients, which may also be used to improve the unsatisfactory dissolution behaviors of the previously reported SIN co-amorphous systems. Several hydrogen bonding interactions between SIN and PTM or SULF could be identified in NMR experiments in DMSO-d6, which may be underlying reasons of decreased dissolution behaviors of both co-amorphous forms. These drug-drug co-amorphous systems could be a potential strategy for the treatment of infection-associated RA.

Physical aging of the 62.5GeS2-12.5Sb2S3-25CsCl chalcogenide glass: Assessing the mechanisms of equilibration and crystallization

The goal of this work is to provide an answer to the important scientific question: will a glass-forming liquid reach its equilibrium state or not before to crystallize during physical aging process, i.e. when it is maintained below its glass transition temperature? For this goal the physical aging process in a 62.5GeS2-12.5Sb2S3-25CsCl glass has been investigated for a long period (5 months) at 30°C below the glass transition temperature Tg. A crystallization was observed during this process, and was characterized through X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Temperature Modulated Differential Scanning Calorimetry (MT-DSC) analyses. By evaluating the enthalpy loss related to the physical aging and by comparing this experimental quantity to the theoretical one, we have proved that this glass has reached its thermodynamic equilibrium state before crystallizing. Thus, this work evidences experimentally the ability for a glass former to crystallize under Tg after reaching its equilibrium state.

Efficacy and safety of permeation enhancers: A kinetic evaluation approach and molecular mechanism study in the skin

This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement–low irritation, medium enhancement–high irritation, and low enhancement–low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study. The kinetic parameter, effective-safety index (IES), was proposed to describe the regularity of enhancement effect tendency and irritation risk, and the relationship between IES and physicochemical properties of permeation enhancers was analyzed with multiple regression analysis. According to the results of modulated temperature differential scanning calorimetry and dielectric spectrum, permeation enhancers with high lipophilicity and low polarity had IES > 1, suggesting high enhancement effect and low irritation due to their higher affinity with the stratum corneum (SC) than with epidermis (EP). Permeation enhancers with medium lipophilicity and medium polarity exhibited 0 < IES ≤ 1, showing medium enhancement effect and high irritation, as determined by their comparable affinity with the SC and epidermis (EP). However, permeation enhancers with low lipophilicity and high polarity had IES → 0, demonstrating low enhancement effect and irritation, as indicated by their poor affinity with the SC. In summary, different physicochemical properties of permeation enhancers influenced their affinities with skin layers, resulting in their different enhancement effect and irritation potential. This study will provide a theoretical basis and criteria for evaluating and predicting the safety and efficacy of permeation enhancers, which will enable a more rational selection of permeation enhancers in the optimization of transdermal patches.

Kinetics of enthalpy recovery studied by temperature-modulated differential scanning calorimetry

An analyzing method using periodic temperature modulation is applied to the kinetics of enthalpy recovery that occurs when an amorphous material in the glassy state devitrifies during heating. In particular, this study demonstrates that an analytical expression of the kinetic response can be formulated by assuming temperature modulation with a periodic temperature jump and isothermal holding. This analysis provides a reasonable interpretation for the well-known fact that the magnitude of the dynamic heat capacity of complex quantity obtained by temperature modulation does not exhibit a large peak corresponding to the enthalpy recovery peak. Furthermore, it is demonstrated that the phase angle peak of the dynamic heat capacity was affected by the kinetics. Its quantitative evaluation provides useful information on the relaxation time during glass transition. Numerical simulations and experimental results of atactic polystyrene examined by conventional differential scanning calorimetry and fast scanning calorimetry confirm these findings.

Phase change characterization of eco-friendly isopropyl palmitate-based graphene nanoplatelet nanofluid for thermal energy applications

• Design of stable isopropyl palmitate-based nanoenhanced phase change materials. • Analysis of solid–liquid transition and enthalpy-temperature curves. • Reductions in sub-cooling higher than 2 K, increases in the latent heat up to 5.9%. • The IPP polymorphism was not significantly altered due to the GnPs dispersions. • Reductions up to 12% in the isobaric heat capacities compared to the base material. Thermal energy storage (TES) facilitates the integration of renewable energy by decoupling production and consumption, mitigating intermittence issues. However, current TES systems use fossil fuel-based products as storage media, so the development of sustainable and efficient materials should be investigated. This work aims to the design and characterization of new eco-friendly nanoenhanced phase change materials (NePCMs) based on dispersions of graphene nanoplatelets of two different lateral sizes (7.2 and 40 μm) in isopropyl palmitate for cold storage applications. The stability of the NePCMs was analysed by dynamic light scattering, selecting Span® 80 as surfactant to improve the stabilization of both nanomaterials within the base material. The influence of the nanoadditive concentration on the temperature transitions and on the solid–liquid phase change were comprehensively studied by differential scanning calorimetry, finding out that the dispersed nanoadditives do not alter the polymorphism of the isopropyl palmitate. Additionally, reductions in the sub-cooling effect higher than 2 K for both nanoplatelets were found, with increases in the latent heat up to 5.9 and 3.9% for the shorter and the longer nanoplatelets, respectively. Isobaric heat capacities were also determined by temperature-modulated differential scanning calorimetry, reporting maximum reductions of 12% compared to the base material.