Scientia Pharmaceutica

Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa. Full article

Telmisartan (Tel) is a potent antihypertensive drug with a very poor aqueous solubility, especially in pH ranging from 3 to 9 (i.e., biological fluids) that results in poor bioavailability. Our aim was to improve Tel solubility and dissolution rates without the need for expensive multistep procedures, and without inclusion of alkalinizers. This study adopted the use of surface solid dispersions (SSDs) employing superdisintegrants, hydrophilic polymers and combined carriers including a superdisintegrant with a hydrophilic polymer. Tel-SSDs were formulated using thesolvent evaporation method. Compatibility between Tel and different carriers was examined via FT-IR. Tel-SSDs were evaluated optically and thermally to reveal a complete loss of the crystalline nature of the drug. Both drug content and percentage yield were calculated to judge the efficiency of the preparation technique used. Saturation, aqueous solubility, and dissolutions rates were determined. Dissolution profiles were studied using model dependent and independent approaches and were subjected to the pair-wise procedure using the DDsolver software program. Effect of aging was studied by comparing the drug content and dissolution profiles of freshly prepared SSDs with aged samples. All Tel-SSDs showed acceptable physical properties. Tel-SSDs showed pertinent enhancement related to the carrier used. Combined surface solid dispersions employing superdisintegrant croscarmellose sodium with either hydrophilic polymer PEG 4000 or Poloxamer 407 gave remarkable enhancement in solubility and dissolution rates of Tel where more than 90% of the drug was released within 20 min. The effect of aging results proved a non-significant difference in the drug content and dissolution profiles between fresh and aged samples. Formulation of Tel SSDs using combined carriers proved to be effective in enhancing the aqueous solubility and dissolution rates of Tel, as well as showing good stability upon aging. Full article

Most human fungal infections exhibit significant defensive oxidative stress responses, which contribute to their pathogenicity. An important component of these reactions is the activation of catalase for detoxification. To discover new antifungal chemicals, the antifungal activity of methanol extracts of Moringa oleifera from two commercial products (Akuanandi and Mas Lait) was investigated. The methanolic extracts’ activity against Sporothrix schenckii was determined using an assay for minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC). The MIC concentrations varied between 0.5 μg/mL and 8 μg/mL. Akuanandi extract had the lowest MIC (0.5 μg/mL) and MLC (1 μg/mL) values. M. oleifera methanolic extracts were tested for catalase inhibition. The Ki values of the M. oleifera extract against S. schenckii catalase (SsCAT) was found to be 0.7 μg/mL for MOE-AK and 0.08 μg/mL for MOE-ML. Catalase’s 3D structure in SsCAT is unknown. The homology of SsCAT was modeled with an in silico study using a 3D structure from SWISS MODEL and validation the predicted 3D structure was carried out using PROCHECK and MolProbity. Docking simulations were used to analyze protein interactions using Pymol, PoseView, and PLIP. The results revealed that M. oleifera glucosinolates interacts with SsCAT. A molecular interaction analysis revealed two inhibitor compounds (glucosinalbin and glucomoringin) with high binding affinity to key allosteric-site residues. The binding energies revealed that glucosinalbin and glucomoringin bind with high affinity to SsCAT (docking energy values: −9.8 and −9.0 kcal/mol, respectively). The findings of this study suggest that glucosinolates derived from M. oleifera could be used instead of synthetic fungicides to control S. schenckii infections. We hope that the findings of this work will be valuable for developing and testing novel natural anti-sporothrix therapeutic agents in the future. Full article

Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (NSCLC). The adhesion as well as the migration assay was performed. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of αvβ3 integrins, α5β1 integrins, and VEGF. The cells were divided into the following treatment groups: control (non-treated/NT), positive control (AP3/inhibitor β3 80 µg/mL), cisplatin (9 µg/mL), and EEOS at concentrations of 50, 70, 100, and 200 µg/mL. The results showed that EEOS inhibits the adhesion ability and migration of A549 cells, with an optimal concentration of 200 µg/mL. ELISA testing showed that the group of A549 cells given EEOS 200 µg/mL presented a decrease in the optimal expression of integrin α5β1, integrin αvβ3, and VEGF. Full article

Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine. Full article

Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities. Full article

This work was aimed to assess the antidiabetic effect of orally administered Prosochit^®-based nanoparticles of insulin in an animal model. Five batches of insulin-loaded nanoparticles were prepared as dry water-in-oil-in-water emulsions using different emulsifiers (prosopis gum, Prosochit^® 201, Prosochit^® 101, Prosochit^® 102, and chitosan) for the outer emulsion. Unloaded Prosochit^® 101-based nanoparticles were also formulated. The morphology and size distribution of the nanoparticles were studied using a scanning electron microscope and Zetasizer. Forty alloxan-induced diabetic Wistar rats were divided into eight groups. The different groups were administered daily with different formulations (unloaded nanoparticles, the 5 loaded nanoparticles equivalent to 50 IU insulin per kg, purified water, and Actrapid) for 14 days. Blood glucose level was monitored and determined over 24 h. Fasting blood sugar was also taken on days 3, 5, 7, and 14. A graph of the percent blood glucose level relative to time 0 h was plotted against time. The particles showed a water-in-oil-in-water constitution. Both the drug-loaded and the unloaded Prosochit^®-based nanoparticles were of nano dimension. There was a significant difference (p < 0.0001) in the antidiabetic effects of all insulin-loaded nanoparticles compared with the negative control. There was no significant difference across the insulin-loaded nanoparticles of prosopis gum, Prosochit^® 201, Prosochit^® 102, and chitosan while the insulin-loaded Prosochit^® 101 nanoparticles showed the best activity, which is comparable to subcutaneous insulin, reducing blood glucose levels to 32.20 ± 3.79%. All the oral Prosochit^®-based insulin nanoparticles are characterized by appreciable antidiabetic activity with the activity of Prosochit^® 101-based nanoformulation being comparable to that of the subcutaneous insulin. Full article

Simultaneous determination of the tandem of drugs, like meldonium and metoprolol, with enormous polarity differences between them, requires thorough research and careful selection of chromatographic conditions. The three different CN-cyano groups with link-based particle columns, LiChrospher CN, Waters Spherisorb CNRP, Zorbax CN SB stationary phases, were tested, in an isocratic elution system, with a running mobile phase containing various concepts of composition contents. They were first with buffering salts which included acetonitrile and ammonium phosphate in one group, and then without buffering salts but with diluted acids, composed of acetonitrile and diluted acids as the second group. We can conclude that the most optimal concepts, in terms of expressiveness and environmental friendliness, were concepts using of column Zorbax CN SB (4.6 mm i.d. × 250 mm, 5 μm) and mobile phase ACN—0.15% NH₄H₂PO₄ (50:50 and 60:40, v/v). There are very poor available data about ideas and usable information about the development of methods for simultaneous determination of these two active substances with polarity differences between them. We suggest that our work offered detailed and successful solutions for the mentioned aim using less sophisticated equipment for quality control and a lab for routine manufacturing control. Full article

In traditional medicine, Cucurbita pepo L. is used for the treatment of rheumatism, diabetes, inflammations, and wound injuries. This study was conducted to evaluate the phytochemical constituents, safety profile, wound healing, and anti-inflammatory activities of Cucurbita pepo leaf extract in rats. The phytochemical analysis of C. pepo extract was carried out using gas chromatography-mass spectrometry (GC-MS). In acute toxicity tests, the rats orally received a single dose of 5 g/kg extract of C. pepo. In a subacute toxicity study, the rats received 200, 400, and 800 mg/kg of the C. pepo extract via daily gavage for 14 days. Bioactive compounds 1-octen-3-ol, nonanal, trans-β-ionone, phytol, trans-farnesol, and squalene were identified. There were no toxic effects detected in any of the evaluated parameters, namely liver, kidney, haematological, lipid, and antioxidant enzymes. In wound healing, C. pepo extract showed greater % wound contraction and tensile strength, as well as reduced wound healing time (12 days) and epithelialization when compared to the control (normal saline) and povidone-iodine treated groups. Rats treated with C. pepo extract elicit anti-inflammatory activity. The findings of this study revealed that the C. pepo extract has wound healing and anti-inflammatory properties with a wide margin of safety. Full article

In this work, twelve analogues of piperidine alkaloids (-)-cassine and (-)-spectaline were synthesized, as well as the racemic forms of these natural products. The compounds were evaluated for their inhibition of electric eel acetylcholinesterase (AChE_ee) and human butyrylcholinesterase (BChE_hu) by on-flow mass-spectrometry-based dual-enzyme assay, and the inhibition mechanisms for the most potent analogues were also determined. Our results showed a preference for BChE_hu inhibition with compounds 10c (Ki = 5.24 μM), 12b (Ki = 17.4 μM), 13a (Ki = 13.2 μM) and 3 (Ki = 11.3 μM) displaying the best inhibitory activities. Full article

Antioxidants are widely used in pharmaceutical industries. Gelatin is a byproduct of the meat industry and its hydrolysates showed several functionalities, such as antioxidant activity. The purpose of this study was to describe and optimize the enzymatic hydrolysis conditions including time, temperature, pH, and enzyme/substrate ratio (E/S) to produce protein hydrolysate with antioxidant functionality from bovine gelatin by RSM; the scavenging activity was evaluated using the DPPH method. The model observed was fitted with desirable adequacy and sufficiency. We found that the antioxidant activity increased significantly (p < 0.05) with the increase in pH value, E/S ratio, and time of enzymatic process; however, the temperature had no significant (p < 0.05) effect on the antioxidant activity of the hydrolysate. The optimum hydrolysis conditions were observed at a temperature of 35.3 °C, pH of 8.0, and E/S ratio at 2.5 after 2 h hydrolysis by trypsin enzyme. The results showed that the hydrolysate under these conditions, optimized by RSM, could be more effective on antioxidant activity. Regarding the antioxidant potential, gelatin hydrolysate can be used as an antioxidant supplement in pharmaceutical industries. Full article

Zinc oxide nanoparticles (ZnO NPs) modified by oxopyrymidine alcohol, also known as xymedone (Xym), were obtained and studied using FTIR, UV-vis, and fluorescent spectroscopy, and SEM, BET, powder XRD, and DLS analysis. A formulation of thixotropic hydrophilic gels containing Carbopol-based Xym and ZnO NPs was developed. A vertical Franz cell with a cellulose acetate membrane was used as a model to investigate the passive diffusion of the gel components by AAS. The gel components—Xym and ZnO NPs—were shown to penetrate through acetyl cellulose membrane within 5–7 h depending on an initial amount, and its values were in the range of 56–77%. The penetration of modified ZnO NPs by Xym was more effective in contrast to ZnO NPs without modification. The burn wound healing activity of ZnO NPs–Xym gel was demonstrated on a thermal burn wound model on rats. SOD and GR activity was increased by 30–35% during ZnO NPs–Xym gel treatment, the burn area on 10 postburn day decreased by 10% in contrast to a positive control, Methyluracyl^®® ointment. Full article

Silver nanoparticles (AgNPs) have broad biocidal activities, and are widely employed as an active ingredient in antiseptic, anti-viral, and anti-inflammatory preparations. Green-synthesizing AgNPs would be a rapid, cheap, and environmentally friendly method of synthesis. The methanolic extract of the leaves of Bellevalia flexuosa Boiss. (Asparagaceae) was used for the green synthesis of the AgNPs. The effects of the pH and the concentration of silver nitrate (AgNO₃) on the synthesis of the AgNPs were investigated. The AgNPs produced above pH 10, and 1 mM of AgNO₃ resulted in lower hydrodynamic diameters. Ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction proved the formation of the AgNPs, with a face-centered, cubed geometry. Scanning electron microscopy images showed colloidal and well-dispersed nanoparticles. In addition, the antibacterial activities of the prepared AgNPs were assessed by optical densities (ODs) against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The broths of Gram-negative and Gram-positive bacteria that contained AgNPs, showed lower OD values compared to the controls. In conclusion, AgNPs were prepared using B. flexuosa methanolic extract, and showed antibacterial activity against the tested bacterial strains. Full article

This study aimed to investigate the ability of brown Agaricus bisporus extracts to enhance xerosis treatment via their biological activities, including their antioxidant, anti-aging, and anti-inflammation. Brown A. bisporus ethanol extract (EE) and brown A. bisporus water extract (WE) contained ergothioneine and gallic acid as their major compounds, as detected by HPLC, respectively. The WE exhibited the highest total polysaccharide content (734.04 ± 0.03 mg glucose/g extract) and total phenolic content (190.90 ± 0.07 mg gallic acid/g extract). The WE exhibited an inhibitory effect of 83.34 ± 18.66% on a collagenase enzyme, whereas the EE inhibited the elastase enzymes by 81.26 ± 4.37%. In addition, the EE also demonstrated strong activities against DPPH, with an IC₅₀ 0.30 ± 0.04 mg/mL, ABTS with a TEAC value of 8.06 ± 0.08 µM Trolox/g extract, and a FRAP assay with a FRAP value of 390.50 ± 0.32 mM FeSO₄/g. In addition, all extracts were non-cytotoxic and could decrease the secretion of IL-6 and TNF-α in HaCaT cells. Therefore, brown A. bisporus extracts might be a potential natural raw material that can be further used in cosmeceutical products for xerosis treatment due to their good efficacy. Full article

(1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x10⁶), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (p < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity. Full article

Aromatic essential oils play a significant role in pharmaceuticals, food additives, cosmetics, and perfumery. Essential oils mostly comprise aliphatic hydrocarbons, monoterpenoids, sesquiterpenoids and diterpenes. Plant extracts comprise a complex mixture of terpenes, terpenoids, aliphatic and phenol-derived aromatic components. Terpenes are a significant class of hydrocarbons with numerous health benefits. These biological functions of essential oil components are examined in vitro and in vivo studies. Some studies evaluated the properties and functions of α-phellandrene (α-PHE). Detailed evaluation to determine the functions of α-PHE over a spectrum of health care domains needs to be initiated. Its possible mechanism of action in a biological system could reveal the future opportunities and challenges in using α-PHE as a pharmaceutical candidate. The biological functions of α-PHE are reported, including anti-microbial, insecticidal, anti-inflammatory, anti-cancer, wound healing, analgesic, and neuronal responses. The present narrative review summarizes the synthesis, biotransformation, atmospheric emission, properties, and biological activities of α-PHE. The literature review suggests that extended pre-clinical studies are necessary to develop α-PHE-based adjuvant therapeutic approaches. Full article

It was determined that the studied 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) affects the cyclooxygenase pathway of the arachidonic acid cascade, the markers of damage to neurons on models of PTZ kindling. In the model of chronic epileptogenesis in mice (pentylenetetrazole kindling), a 4-thiazolidinone derivative showed high anticonvulsant activity, which is weaker than the effect of sodium valproate and higher than Celecoxib. The mentioned compound has a pronounced anti-inflammatory effect in the brain on the background of the PTZ kindling, reliably inhibiting COX-1 and COX-2. The predominant inhibition of COX-2 by 44.5% indicates this enzyme’s high selectivity of Les-6222. According to the molecular docking study results, the studied compound revealed the properties of COX-1/COX-2 inhibitor and especially 5-LOX/FLAP. The decreasing content of 8-isoprostane in the brain of mice of the Les-6222 group indicates a beneficial effect on cell membranes in the background of oxidative stress during the long-term administration of PTZ. In addition, Les-6222 significantly decreased the content of neuron-specific enolase, indicating neuroprotective properties in the background of chronic epileptogenesis. The obtained results experimentally substantiate the feasibility of further developing Les-6222 as a promising anticonvulsant agent. Full article

Globally, obesity is a serious health concern that causes numerous diseases, including type 2 diabetes, hypertension, cardiovascular diseases, etc. Medicinal plants have been used to aid in weight loss since ancient times. Thus, this research is focused on the exploration of pancreatic lipase inhibitory activity and secondary metabolite profiling of Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica, selected based on an ethnobotanical survey. The lipase inhibition was investigated using 4-nitrophenyl butyrate (p-NPB) as a substrate. To uncover further therapeutic potentials of these medicinal plants, antimicrobial activity and minimum inhibitory concentration (MIC) of the extracts were also determined. The ethyl acetate plant extracts showed higher antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Shigella sonnei. The MIC of ethyl acetate extracts of medicinal plants considered in this study ranges from 1.56 to 6.25 mg/mL. The hexane fraction of Mimosa pudica and Phyllanthus emblica showed a higher lipase inhibitory activity as compared to others, with IC₅₀ values of 0.49 ± 0.02 and 2.45 ± 0.003 mg/mL, respectively. In the case of Bergenia ciliata, the methanolic extract inhibited lipase more effectively than others, with an IC₅₀ value of 1.55 ± 0.02 mg/mL (IC₅₀ value of orlistat was 179.70 ± 3.60 µg/mL). A mass spectrometry analysis of various solvent/solvent partition fractions (extracts) revealed 29 major secondary metabolites. The research offers a multitude of evidence for using medicinal plants as antiobesity and antimicrobial agents. Full article

The most challenging step in developing bioanalytical methods is finding the best sample preparation method. The matrix interference effect of biological sample become a reason of that. Molecularly imprinted SERS become a potential analytical method to be developed to answer this challenge. In this article, we review recent progress in MIP SERS application particularly in bioanalysis. Begin with the explanation about molecular imprinting technique and component, SERS principle, the combination of MIP SERS, and follow by various application of MIP SERS for analysis. Finally, the conclusion and future perspective were also discussed. Full article