Pharmaceutical Applications Research Articles

Liposomes in the cosmetics: present and outlook.

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

Naturally Occurring Norsteroids and Their Design and Pharmaceutical Application

Naturally Occurring Norsteroids and Their Design and Pharmaceutical Application

Display Technologies for Expanding the Pharmaceutical Applications of Cyclotides

Display Technologies for Expanding the Pharmaceutical Applications of Cyclotides

Chemical Characterization of Terpene-Based Hydrophobic Eutectic Solvents and Their Application for Pb(II) Complexation during Solvent Extraction Procedure

Solvents prepared from natural terpenes (menthol and thymol), as H-bond acceptors, and a series of organic acids (chain lengths of 8, 10, and 14 C atoms), as H-bond donors, were characterized and tested as reaction media for liquid–liquid extraction purposes. Due to their high hydrophobicity, they seem to be promising alternatives to conventional (nonpolar and toxic) solvents, since they possess relatively less toxic, less volatile, and consequently, more environmentally friendly characteristics. Assuming that the equilibrium is established between solvent and analyte during a ligandless procedure, it can be concluded that those nonpolar solvents can efficiently extract nonpolar analytes from the aqueous environment. Previous investigations showed a wide range of applications, including their use as solvents in extractions of metal cations, small molecules, and bioactive compounds for food and pharmaceutical applications. In this work, hydrophobic solvents based on natural terpenes, which showed chemical stability and desirable physicochemical and thermal properties, were chosen as potential reaction media in the liquid–liquid extraction (LLE) procedure for Pb(II) removal from aqueous solutions. Low viscosities and high hydrophobicities of prepared solvents were confirmed as desirable properties for their application. Extraction parameters were optimized, and chosen solvents were applied. The results showed satisfactory extraction efficiencies in simple and fast procedures, followed by low solvent consumption. The best results (98%) were obtained by the thymol-based solvent, thymol–decanoic acid (Thy-DecA) 1:1, followed by L-menthol-based solvents: menthol–octanoic acid (Men-OctA) 1:1 with 97% and menthol–decanoic acid (Men-DecA) 1:1 with 94.3% efficiency.

Exploring expected values of topological indices of random cyclodecane chains for chemical insights

Chemical graph theory has made a significant contribution to understand the chemical compound properties in the modern era of chemical science. At present, calculation of the topological indices is one of most important area of research in the field of chemical graph theory. Cyclodecane is a cyclic hydrocarbon with the chemical formula C10H20\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$C_{10}H_{20}$$\\end{document}. It consists of a ring of ten carbon atoms bonded together in a cyclical structure. Cyclodecane chains can be part of larger molecules or polymers, where multiple cyclodecane rings are connected together. These molecules can have various applications in chemistry, materials science, and pharmaceuticals. This article aims to determine expected values of some connectivity based topological indices of random cyclodecane chains, containing saturated hydrocarbons with at least two rings. It also compares these descriptors using explicit formulae, numerical tables and present graphical profiles of these comparisons.

[Accepted, unedited version] The dark side of drug repurposing, from clinical trial challenges to antimicrobial resistance: analysis based on three major fields

Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implement- ing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to con- duct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields cardiovascular, cancer and diabetes and to further underscore the potential risks associated with the emergence of antimicrobial resistance when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By com- prehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.

Bioactivities of Jojoba Oil Beyond Skincare.

Jojoba oil, which is extracted from jojoba plant seeds that are native to North America, possesses a unique molecular structure and is distinct from other oils. Unlike typical oils, which mostly contain triglycerides, jojoba oil is composed of long monounsaturated esters, affording it exceptional properties and is valuable across cosmetics, chemicals, and pharmaceuticals. While jojoba oil is prevalent in beauty and skincare today, its seeds and oil have ancient roots in folk medicine, used for treating skin and scalp issues, wounds, sore throats, obesity, and even cancer, while enhancing immunity and fostering hair growth. Modern research underscores jojoba oil's pharmacological versatility, demonstrating antioxidant, antidiabetic, anti-acne, anti-inflammatory, antipyretic, and antibacterial properties. Notably, there has been a surge in its utilization in pharmaceuticals, particularly in topical, transdermal, and parenteral formulations. This review provides a comprehensive overview of jojoba oil, encompassing its chemical composition, extraction techniques, health advantages, and pharmaceutical application developments.

[Atomic Force Microscopy to Measure the Mechanical Property of Nanosized Lipid Vesicles and Its Applications].

Nanoparticles, including liposomes and lipid nanoparticles, have garnered global attention due to their potential applications in pharmaceuticals, vaccines, and gene therapies. These particles enable targeted delivery of new drug modalities such as highly active small molecules and nucleic acids. However, for widespread use of nanoparticle-based formulations, it is crucial to comprehensively analyze their characteristics to ensure both efficacy and safety, as well as enable consistent production. In this context, this review focuses on our research using atomic force microscopy (AFM) to study liposomes and lipid nanoparticles. Our work significantly contributes to the capability of AFM to measure various types of liposomes in an aqueous medium, providing valuable insights into the mechanical properties of these nanoparticles. We discuss the applications of this AFM technique in assessing the quality of nanoparticle-based pharmaceuticals and developing membrane-active peptides.

Quantitative analysis of molecular interactions in κ-carrageenan-Isovanillin biocomposite for biodegradable packaging and pharmaceutical applications using NMR, TOF-SIMS, and XPS approach

Quantitative analysis of molecular interactions in κ-carrageenan-Isovanillin biocomposite for biodegradable packaging and pharmaceutical applications using NMR, TOF-SIMS, and XPS approach

Phlomis crinita Cav. from Algeria: A source of bioactive compounds possessing antioxidant and wound healing activities.

Phlomis crinita Cav. (Lamiaceae), locally known as "El Khayata" or "Kayat El Adjarah", is traditionally used in Algeria for its wound-healing properties. Investigate, for the first time, the phytochemical profile, safety, antioxidant and wound-healing activities of the flowering tops methanolic extract of P. crinita (PCME) collected from Bouira Province in the North of Algeria. Preliminary phytochemical assays were carried out on PCME to quantify the main classes of bioactive compounds, such as total phenols, flavonoids, and tannins. An in-depth LC-DAD-ESI-MS analysis was carried out to elucidate the phytochemical profile of this plant species. Antioxidant activity was investigated by several colorimetric and fluorimetric assays (DPPH, TEAC, FRAP, ORAC, β-carotene bleaching and ferrozine assay). The acute oral toxicity of PCME (2000 mg/kg b.w.) was tested in vivo on Swiss albino mice, whereas the acute dermal toxicity and wound-healing properties of the PCME ointment (1-5% PCMO) were tested in vivo on Wistar albino rats. Biochemical and histological analyses were carried out on biological samples. The phytochemical screening highlighted a high content of phenolic compounds (175.49 ± 0.8 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (82.28 ± 0.44 mg of quercetin equivalents/g of dry extract). Fifty-seven compounds were identified by LC-DAD-ESI-MS analysis, belonging mainly to the class of flavones (32.27%), with luteolin 7-(6''-acetylglucoside) as the most abundant compound and phenolic acids (32.54%), with salvianolic acid C as the most abundant compound. A conspicuous presence of phenylethanoids (15.26%) was also found, of which the major constituent is forsythoside B. PCME showed a strong antioxidant activity with half-inhibitory activity (IC50) ranging from 1.88 to 37.88 μg/mL and a moderate iron chelating activity (IC50 327.44 μg/mL). PCME appears to be safe with Lethal Dose 50 (LD50) ≥ 2000 mg/kg b.w. No mortality or toxicity signs, including any statistically significant changes in body weight gain and relative organs' weight with respect to the control group, were recorded. A significant (p < 0.001) wound contraction was observed in the 5% PCMO-treated group with respect to the untreated and petroleum jelly groups between 8 and 20 days, whereas no statistically significant results were observed at the two lower doses (1 and 2% PCMO). In addition, the 5% PCMO-treated group showed a statistically significant (p < 0.05) wound healing activity with respect to the reference drug-treated group, showing, at the end of the study, the highest wound contraction percentage (88.00 ± 0.16%). PCME was safe and showed strong antioxidant and wound-healing properties, suggesting new interesting pharmaceutical applications for P. crinita based on its traditional use.

Engineering tRNAs for the Ribosomal Translation of Non-proteinogenic Monomers.

Ribosome-dependent protein biosynthesis is an essential cellular process mediated by transfer RNAs (tRNAs). Generally, ribosomally synthesized proteins are limited to the 22 proteinogenic amino acids (pAAs: 20 l-α-amino acids present in the standard genetic code, selenocysteine, and pyrrolysine). However, engineering tRNAs for the ribosomal incorporation of non-proteinogenic monomers (npMs) as building blocks has led to the creation of unique polypeptides with broad applications in cellular biology, material science, spectroscopy, and pharmaceuticals. Ribosomal polymerization of these engineered polypeptides presents a variety of challenges for biochemists, as translation efficiency and fidelity is often insufficient when employing npMs. In this Review, we will focus on the methodologies for engineering tRNAs to overcome these issues and explore recent advances both in vitro and in vivo. These efforts include increasing orthogonality, recruiting essential translation factors, and creation of expanded genetic codes. After our review on the biochemical optimizations of tRNAs, we provide examples of their use in genetic code manipulation, with a focus on the in vitro discovery of bioactive macrocyclic peptides containing npMs. Finally, an analysis of the current state of tRNA engineering is presented, along with existing challenges and future perspectives for the field.

Synthesis of MPEG-b-PLLA Diblock Copolymers and Their Crystallization Performance with PDLA and PLLA Composite Films

Methoxy poly(ethylene glycol)-block-poly(L-lactide) (MPEG-b-PLLA) has a wide range of applications in pharmaceuticals and biology, and its structure and morphology have been thoroughly studied. In the experiment, we synthesized MPEG-b-PLLA with different block lengths using the principle of ring-opening polymerization by controlling the amount of lactic acid added. The thermodynamic properties of copolymers and the crystallization properties of blends were studied separately. The crystallization kinetics of PDLA/MPEG-b-PLA and PLLA/MPEG-b-PLA composite films were studied using differential scanning calorimetry (DSC). The results indicate that the crystallization kinetics of composite films are closely related to the amount of block addition. The crystallinity of the sample first increases and then decreases with an increase in MPEG-b-PLLA content. These results were also confirmed in polarized optical microscope (POM) and wide-angle X-ray diffraction (WAXD) tests. When 3% MPEG-b-PLLA was added to the PDLA matrix, the blend exhibited the strongest crystallization performance.

Impact of Drying Method and Solvent Extraction on Ethiopian Verbascum sinaiticum (Qetetina) Leaves: Metabolite Profiling and Evaluation of Antioxidant Capacity

The aim of this study was to evaluate the effects of different drying methods on bioactive compounds and to analyze their composition in Verbascum sinaiticum (V. sinaiticum) leaf extracts using UHPLC-ESI-QTOF-MS/MS. V. sinaiticum is traditionally used as an herbal medicine, yet it has undergone limited scientific investigations regarding its secondary metabolites. V. sinaiticum leaves were dried using oven dryers at 50 °C, 60 °C, and 70 °C, as well as a freeze dryer. The leaves were then extracted using 50% and 70% aqueous ethanol and 100% aqueous solutions. The results showed that the highest contents of TPC and TFC were observed when 70% aqueous ethanol was used during freeze drying, reaching 181.73 mg GAE/g dw and 78.57 mg CE/g dw, respectively. The strongest correlations were observed between the TFC and DPPH radical scavenging activity (0.9082), followed by TPC and ABTS assays (0.8933) and TPC and DPPH (0.8272). In the FTIR analysis, freeze drying exhibited a lower intensity of the phenolic -OH functional groups, contrasting with significant denaturation observed during oven drying at 70 °C. Metabolite analysis identified 29 compounds in V. sinaiticum leaves, further confirming the presence of 14 phenolic and flavonoid compounds, including kaempferol, catechin, gallic acid, and myricetin derivatives, consistent with the experimentally observed antioxidant capacity. This study highlights the impact of drying methods on the bioactive composition of V. sinaiticum and underscores its potential as a source of antioxidants for food, nutraceutical, and pharmaceutical applications.

Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss

Abstract The present study evaluated the potential of Salvia balansae from the Aures Mountains as a source of natural bioactive compounds. Leaves, flowers, and stems were extracted separately using methanol, ethanol, and acetone. Phenolic compounds were quantified colorimetrically and identified using liquid chromatography coupled with mass spectrometry (LC-MS). Antioxidant capacity was assessed using six different in vitro assays, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, 1,1-diphenyl-1-picrylhydrazyl, cupric reducing antioxidant capacity, ferric reducing antioxidant power, ferrous ion chelating, and phenanthroline assay, while the photo-protective capacity was evaluated using the sun protective factor. The methanolic flower extracts revealed the highest O-diphenol and phenolic levels (287.9 ± 0.50 and 147.87 ± 0.21 µg GAE/mg, respectively), whereas the acetonic and ethanolic leaf extracts contained the highest flavonoid (72.17 ± 0.12 μg QE/mg) and flavonol (35.28 ± 0.05 μg QE/mg) levels, respectively. LC-MS was used to identify 18 phenolics, including quinic acid (5.051–69.69 ppm), luteolin-7-o-glucoside (7.802–44.917 ppm), apigenin-7-o-glucoside (3.751–68.507 ppm), and cirsiliol (2.081–15.608 ppm), distinguishing this Aures taxon. Principal component analysis and unweighted pair-group method with arithmetic mean revealed variability in phytochemicals, antioxidant properties, and photo-protective activity influenced by biological activities and the compound content. Overall, S. balansae demonstrated promising photo-protective capacity, the presence of key bioactive compounds, and wide-ranging antioxidant potential, presenting this endemic plant as a valuable source of natural antioxidants and photo-protective agents with pharmaceutical and cosmetic applications.

Machine Learning-Based Prediction of Reduction Potentials for PtIV Complexes.

Some of the well-known drawbacks of clinically approved PtII complexes can be overcome using six-coordinate PtIV complexes as inert prodrugs, which release the corresponding four-coordinate active PtII species upon reduction by cellular reducing agents. Therefore, the key factor of PtIV prodrug mechanism of action is their tendency to be reduced which, when the involved mechanism is of outer-sphere type, is measured by the value of the reduction potential. Machine learning (ML) models can be used to effectively capture intricate relationships within PtIV complex data, leading to highly accurate predictions of reduction potentials and other properties, and offering significant insights into their electrochemical behavior and potential applications. In this study, a machine learning-based approach for predicting the reduction potentials of PtIV complexes based on relevant molecular descriptors is presented. Leveraging a data set of experimentally determined reduction potentials and a diverse range of molecular descriptors, the proposed model demonstrates remarkable predictive accuracy (MSE = 0.016 V2, RMSE = 0.13 V, R2 = 0.92). Ab initio calculations and a set of different machine learning algorithms and feature engineering techniques have been employed to systematically explore the relationship between molecular structure and similarity and reduction potential. Specifically, it has been investigated whether the reduction potential of these compounds can be described by combining ML models across different combinations of constitutional, topological, and electronic molecular descriptors. Our results not only provide insights into the crucial factors influencing reduction potentials but also offer a rapid and effective tool for the rational design of PtIV complexes with tailored electrochemical properties for pharmaceutical applications. This approach has the potential to significantly expedite the development and screening of novel PtIV prodrug candidates. The analysis of principal components and key features extracted from the model highlights the significance of structural descriptors of the 2D Atom Pairs type and the lowest unoccupied molecular orbital energy. Specifically, with just 20 appropriately selected descriptors, a notable separation of complexes based on their reduction potential value is achieved.

Characterization of Surfactant Spheroidal Micelle Structure for Pharmaceutical Applications: A Novel Analytical Framework

We introduce an innovative theoretical framework tailored for the analysis of Pair Distribution Function (PDF) data derived from Small-Angle X-ray Scattering (SAXS) measurements of core-shell micelles. The new approach involves the exploitation of the first derivative of the PDF and the derivation of analytical equations to solve the core-shell micelle structure under the hypothesis of a spheroidal shape. These analytical equations enable us to determine the micelle’s aggregation number, degree of ellipticity, and contrast in electron density between the core-shell and shell-buffer regions after having determined the whole micelle size and its shell size from the analysis of the first derivative of the PDF. We have formulated an overdetermined system of analytical equations based on the unknowns that characterize the micelle structure. This allows us to establish a Figure of Merit, which is utilized to identify the most reliable solution within the system of equations.

Development and characterization of camel gelatin films: Influence of camel bone age and glycerol or sorbitol on film properties

This study developed and evaluated camel bone gelatin films (CBGFs) with glycerol or sorbitol as plasticizers. Gelatin extracted from the bones of camels (Camelus dromedarius) at ages ranging from 2.5 to 7 years was used. A comprehensive analysis was conducted, evaluating a range of properties including thickness, moisture sorption capacity, water vapor permeability (WVP), infrared spectral characteristics, light absorption behavior, solubility, as well as mechanical and thermal attributes. This thorough examination allowed for a nuanced understanding of the diverse characteristics exhibited by the camel gelatin samples across different age groups. The results indicated that camel age, glycerol, and sorbitol had a significant impact on the properties of the film (P < 0.05). Tensile strength ranged from 0.32 MPa to 3.99 MPa, while the percentage of elongation at break varied from 89.42 % to 2.68 %. Film color (lightness, L) ranged from 21.39 to 41.33. Glycerol and sorbitol plasticized films were 100 % water soluble. Moisture sorption increased with temperature (25 °C, 35 °C, and 45 °C), with sorbitol films retaining less water. WVP was low in films from old camel bones and high in glycerol-plasticized CBGF-2.5Y and CBGF-4.5Y. Thermal analysis showed a melting temperature between 158.60 °C and 174.10 °C, depending on bone age and plasticizer. These films demonstrate promise for use in food packaging, coatings, and pharmaceutical applications.

Estimation of genetic diversity utilizing gene-targeted SCoT markers and morpho-chemotypic analyses in Senna alexandrina Mill. (Senna)

Senna, an industrial crop that generates foreign exchange, is planted predominantly in southern India. Senna leaves and pods grown in India are valued in international trade and the global market because they contain a high concentration of the chemical component sennosides. The current investigation was conducted in the CSIR-CIMAP experimental farm in Hyderabad, India. The experiment was designed in an RCBD and replicated three times using twenty-five senna accessions in the years 2020–21 and 2021–22. The combined ANOVA found that all fourteen of the traits studied were highly significant. The D2 analysis and λ1-λ2 values classified the 25 accessions into five clusters with 91.05 % diversity. The molecular diversity was also examined using SCoT markers. As SCoT markers target expressed portions of the genome, the variation among accessions reflects some of the morphological changes among them. For pharmaceutical applications, various lines Gen-1 and 2 (high in Sennosides A and B content) and Gen-4 can be hybridized with Gen-5 and 25 to produce generations high in pharmaceutically relevant Sennosides A and B. Considering genotypes Gen 1 and 2 rank first and second in terms of sennoside A and B contents in leaves (%) and pods, these two genotypes can be employed for large-scale cultivation and to transfer favorable traits in future breeding programs.

Chitosan-Based Nanocarriers for Pulmonary and Intranasal Drug Delivery Systems: A Comprehensive Overview of their Applications.

The optimization of respiratory health is important, and one avenue for achieving this is through the application of both Pulmonary Drug Delivery System (PDDS) and Intranasal Delivery (IND). PDDS offers immediate delivery of medication to the respiratory system, providing advantages, such as sustained regional drug concentration, tunable drug release, extended duration of action, and enhanced patient compliance. IND, renowned for its non-invasive nature and swift onset of action, presents a promising path for advancement. Modern PDDS and IND utilize various polymers, among which Chitosan (CS) stands out. CS is a biocompatible and biodegradable polysaccharide with unique physicochemical properties, making it well-suited for medical and pharmaceutical applications. The multiple positively charged amino groups present in CS facilitate its interaction with negatively charged mucous membranes, allowing CS to adsorb easily onto the mucosal surface. In addition, CS-based nanocarriers have been an important topic of research. Polymeric Nanoparticles (NPs), liposomes, dendrimers, microspheres, nanoemulsions, Solid Lipid Nanoparticles (SLNs), carbon nanotubes, and modified effective targeting systems compete as important ways of increasing pulmonary drug delivery with chitosan. This review covers the latest findings on CS-based nanocarriers and their applications.

Structural Elucidation of Glycosaminoglycans in the Tissue of Flounder and Isolation of Chondroitin Sulfate C

Glycosaminoglycans (GAGs) are valuable bioactive polysaccharides with promising biomedical and pharmaceutical applications. In this study, we analyzed GAGs using HPLC-MS/MS from the bone (B), muscle (M), skin (S), and viscera (V) of Scophthalmus maximus (SM), Paralichthysi (P), Limanda ferruginea (LF), Cleisthenes herzensteini (G), Platichthys bicoloratus (PB), Pleuronichthys cornutus (PC), and Cleisthenes herzensteini (CH). Unsaturated disaccharide products were obtained by enzymatic hydrolysis of the GAGs and subjected to compositional analysis of chondroitin sulfate (CS), heparin sulfate (HS), and hyaluronic acid (HA), including the sulfation degree of CS and HS, as well as the content of each GAG. The contents of GAGs in the tissues and the sulfation degree differed significantly among the fish. The bone of S. maximus contained more than 12 μg of CS per mg of dry tissue. Although the fish typically contained high levels of CSA (CS-4S), some fish bone tissue exhibited elevated levels of CSC (CS-6S). The HS content was found to range from 10–150 ug/g, primarily distributed in viscera, with a predominant non-sulfated structure (HS-0S). The structure of HA is well-defined without sulfation modification. These analytical results are independent of biological classification. We provide a high-throughput rapid detection method for tissue samples using HPLC-MS/MS to rapidly screen ideal sources of GAG. On this basis, four kinds of CS were prepared and purified from flounder bone, and their molecular weight was determined to be 23–28 kDa by HPGPC-MALLS, and the disaccharide component unit was dominated by CS-6S, which is a potential substitute for CSC derived from shark cartilage.