Cymbopogon citratus (DC) stapf. (Gramineae) is a herb known worldwide as lemongrass. The oil obtained, i.e., lemongrass oil has emerged as one among the most relevant natural oils in the pharmaceutical industry owing to its extensive pharmacological and therapeutic benefits including antioxidant, antimicrobial, antiviral and anticancer properties. However, its usage in novel formulations is constrained because of its instability and volatility. To address these concerns, the present study aims to formulate lemongrass-loaded SLN (LGSLN) using hot water titration technique. In the Smix, Tween 80 was selected as a surfactant component, while ethanol was taken as a co-surfactant. Different ratios of Smix (1:1, 1:2, 1:3, 2:1 and 3:1) were utilized to formulate LG-loaded SLN. The results indicated the fact that the LGSLN formulation (abbreviated as LGSLN1), containing lipid phase 10% w/w (i.e., LG 3.33% and SA 6.67%), Tween 80 (20% w/w), ethanol (20% w/w) and distilled water (50% w/w), revealed suitable nanometric size (142.3 ± 5.96 nm) with a high zeta potential value (- 29.12 ± 1.7 mV) and a high entrapment efficiency (77.02 ± 8.12%). A rapid drug release (71.65 ± 5.33%) was observed for LGSLN1 in a time span of 24 h. Additionally, the highest values for steady-state flux (Jss; 0.6133 ± 0.0361 mg/cm2/h), permeability coefficient (Kp; 0.4573 ± 0.0141 (cm/h) × 102) and enhancement ratio (Er; 13.50) was also conferred by LGSLN1. Based on in vitro study results, the developed SLN appeared as a potential carrier for enhanced topical administration of lemongrass oil. The observed results also indicated the fact that the phyto-cosmeceutical prospective of the nanolipidic carrier for topical administration of lemongrass oil utilizing pharmaceutically acceptable components can be explored further for widespread clinical applicability.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13205-023-03726-5.

Recombinant human deoxyribonuclease I (rhDNase, Pulmozyme®) is the most frequently used mucolytic agent for the symptomatic treatment of cystic fibrosis (CF) lung disease. Conjugation of rhDNase to polyethylene glycol (PEG) has been shown to greatly prolong its residence time in the lungs and improve its therapeutic efficacy in mice. To present an added value over current rhDNase treatment, PEGylated rhDNase needs to be efficiently and less frequently administrated by aerosolization and possibly at higher concentrations than existing rhDNase. In this study, the effects of PEGylation on the thermodynamic stability of rhDNase was investigated using linear 20 kDa, linear 30 kDa and 2-armed 40 kDa PEGs. The suitability of PEG30-rhDNase to electrohydrodynamic atomization (electrospraying) as well as the feasibility of using two vibrating mesh nebulizers, the optimized eFlow® Technology nebulizer (eFlow) and Innospire Go, at varying protein concentrations were investigated. PEGylation was shown to destabilize rhDNase upon chemical-induced denaturation and ethanol exposure. Yet, PEG30-rhDNase was stable enough to withstand aerosolization stresses using the eFlow and Innospire Go nebulizers even at higher concentrations (5 mg of protein per ml) than conventional rhDNase formulation (1 mg/ml). High aerosol output (up to 1.5 ml per min) and excellent aerosol characteristics (up to 83% fine particle fraction) were achieved while preserving protein integrity and enzymatic activity. This work demonstrates the technical feasibility of PEG-rhDNase nebulization with advanced vibrating membrane nebulizers, encouraging further pharmaceutical and clinical developments of a long-acting PEGylated alternative to rhDNase for treating patients with CF.

Biopharmaceuticals, such as monoclonal antibodies, are considered as life-saving drugs for autoimmune diseases, cancer and infectious diseases. However, biotherapeutics tend to undergo chemical degradation during various stages of manufacturing. The conditions of chemical degradation, along with the physical degradation pathways, have a direct influence on the overall stability, safety and efficacy of these therapeutics. While site-specific chemical changes have been well-explored and investigated using various analytical approaches, the resulting conformational and structural changes have not been much studied. Thus, we explored various biophysical techniques for assessing the influence of three representatives forced degradation conditions viz. oxidation, deamidation, and glycation, in a model therapeutic trastuzumab biosimilar. The site-specific modifications caused by these stress conditions were analysed using high resolution mass spectrometry. While their thermodynamic and conformational consequences were investigated by using differential scanning colorimetry (Nano-DSC), circular dichroism (CD) spectroscopy, analytical ultracentrifugation (AUC), and dynamic light scattering (DLS). The investigated stress conditions resulted in reduced thermodynamic stability of mAb, as confirmed using Nano-DSC. Secondary structure analysis performed with CD spectroscopy indicated detectable structural alterations in the beta sheets of stressed samples. DLS and SV-AUC studies demonstrated an enhanced level of aggregation and fragmentation in presence of all stress conditions. Thus, the biophysical analytical toolkits, when used simultaneously, could offer deeper insights into the subtle conformational changes that result from site-specific chemical modifications in mAbs. Hence, these analytical approaches may serve as significant additions to the battery of techniques used for forced degradation analysis of biopharmaceuticals.

DFT calculations are utilized to compare and contrast the substituted aluminum-heterofullerenes, C20-nAln (with n = 1-5) from thermodynamically view point, at density functional theory (DFT). Vibrational frequency analysis confirms that apart from C15Al5, all studied species are true minima. Considering the optimized geometries shows that all heterofullerenes are isolated-pentagon cage and none collapse to open deformed as segregated structure. The highest binding energy (5.56 eV/atom) and absolute heat of atomization (3323.68 kcal mol-1) reveals open-shell C19Al1 as the most stable thermodynamic heterofullerene. The most NICS (0) (isotropic and anisotropic parameters, -49.58 and - 46.47 ppm, respectively) introduces closed-shell C18Al2-2 as the most aromatic structure. Also, closed-shell C16Al4-1 heterofullerene emerges with the most polarizability (307.71 a.u.) and hence activity to interact with the surrounding polar species. The lowest and the highest charge transfer on the surfaces of C20 and C16Al4-2 without weak Al-Al bond, as the worst and the best candidate, respectively, provokes further investigation on impossible and possible application for hydrogen storage, respectively. We wish that the present survey will stimulate new experiments.

DNA G-quadruplexes (G4s) form in relevant genomic regions and intervene in several biological processes, including the modulation of oncogenes expression, and are potential anticancer drug targets. The human KRAS proto-oncogene promoter region contains guanine-rich sequences able to fold into G4 structures. Here, by using circular dichroism and differential scanning calorimetry as complementary physicochemical methodologies, we compared the thermodynamic stability of the G4s formed by a shorter and a longer version of the KRAS promoter sequence, namely 5\'-AGGGCGGTGTGGGAATAGGGAA-3\' (KRAS 22RT) and 5\'-AGGGCGGTGTGGGAAGAGGGAAGAGGGGGAGG-3\' (KRAS 32R). Our results show that the unfolding mechanism of KRAS 32R is more complex than that of KRAS 22RT. The different thermodynamic stability is discussed based on the recently determined NMR structures. The binding properties of TMPyP4 and BRACO-19, two well-known G4-targeting anticancer compounds, to the KRAS G4s were also investigated. The present physicochemical study aims to help in choosing the best G4 target for potential anticancer drugs.

The chemical trends in the thermodynamic stability and band gaps of 980 A2B+B3+X6 halide double perovskites are revealed based on high-throughput first-principles calculations. To accurately predict the stability with respect to phase decomposition, all known metal halides in the Materials Project database are considered as the competing compounds. The energies above the convex hull show that only 112 of 980 double perovskites are stable and 27 double perovskites that had been predicted to be stable in the literature are actually unstable after considering more competing compounds. The stability of these double perovskites is determined mainly by A, X, and B+ elements and increases gradually as A becomes heavier (from Li to Cs) and X becomes lighter (from I to F). The band gaps are determined mainly by X, B+, and B3+ elements, decreasing monotonically as X becomes heavier while changing nonmonotonically as B+ and B3+ change. These chemical trends provide clear instructions for the design of double perovskites with good stability and suitable band gaps for various applications, i.e., through choosing heavier A cations (e.g., large organic cations), stable double perovskites can be designed with band gaps tunable in a wide range of 0-7 eV (infrared to ultraviolet); however, through choosing light X anions, stable double perovskites can be designed with only wide band gaps.

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (Kb) of 1.69 ± 0.15 × 103 M-1 at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal\'s interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

Modified nucleic acids have found profound applications in nucleic acid based technologies such as antisense and antiviral therapies. Previous studies on chemically modified nucleic acids have suggested that modifications incorporated in furanose sugar especially at 2\'-position attribute special properties to nucleic acids when compared to other modifications. 2\'-O-methyl modification to deoxyribose sugars of DNA-RNA hybrids is one such modification that increases nucleic acid stability and has become an attractive class of compounds for potential antisense applications. It has been reported that modification of DNA strands with 2\'-O-methyl group reverses the thermodynamic stability of DNA-RNA hybrid duplexes. Molecular dynamics simulations have been performed on two hybrid duplexes (DR and RD) which differ from each other and 2\'-O-methyl modified counterparts to investigate the effect of 2\'-O-methyl modification on their duplex stability. The results obtained suggest that the modification drives the conformations of both the hybrid duplexes towards A-RNA like conformation. The modified hybrid duplexes exhibit significantly contrasting dynamics and hydration patterns compared to respective parent duplexes. In line with the experimental results, the relative binding free energies suggest that the introduced modifications stabilize the less stable DR hybrid, but destabilize the more stable RD duplex. Binding free energy calculations suggest that the increased hydrophobicity is primarily responsible for the reversal of thermodynamic stability of hybrid duplexes. Free energy component analysis further provides insights into the stability of modified duplexes.