Satisfactory Physicochemical Properties Research Articles

Evaluating sisal fibers as an eco-friendly and cost-efficient alternative to cotton for the Moroccan absorbent hygiene and textile industries

The Moroccan textile and hygiene industries face challenges related to the cost and availability of imported cotton fibers, prompting the exploration of alternative and sustainable solutions. The goal was to replace cotton, which presented a significant challenge for the sector, while maintaining its quality properties. This study aimed to replace the imported cotton fibers in Morocco with sisal fibers, a locally available, cheaper, and durable product that exhibits satisfactory physicochemical properties. To achieve this, sisal fibers were treated with different concentrations of sodium hydroxide (NaOH), sodium chlorite (NaClO₂), and hydrogen peroxide (H₂O₂). Analytical techniques, including Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), Optical Microscopy (OM), and X-ray Diffraction (XRD), were used to assess both sisal and commercial cotton fibers. Laboratory tests, such as pH measurements, water absorption, flammability, and degumming rate, were conducted to evaluate and compare their properties. Among the sisal samples analyzed, those treated with 10 % by weight (wt) NaOH and bleached with NaClO₂ showed satisfactory results. These fibers exhibited a compliant pH, a chemical structure similar to cotton, reduced fiber size, a type I crystal structure with a 0.36 crystallinity index, and improved thermal stability. Additionally, they presented a whitish appearance, softness similar to cotton, good fluid absorption capacity, and flame resistance. This study concluded that cotton fibers can be substituted with sisal fibers in the textile and hygiene industries. Further comprehensive analyses could expand the applicability of sisal fibers to additional sectors.

Diphenyl urea-benzylidene acetohydrazide hybrids as fibroblast growth factor receptor1 inhibitors and anticancer agents.

Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series of FGFR-1 targeting cancer. The designed series was synthesized and submitted to NCI-USA to be screened for their growth inhibitory activity on NCI cancer cell lines. Some of the synthesized hybrids displayed promising growth inhibitory activity on NCI cancer cell lines with a mean GI% between 70.39% and a lethal effect. Compounds 9a, 9i, 9j, and 9n-p were further selected for a five-dose assay and all the tested candidates showed promising antiproliferative activity with GI50 reaching the submicromolar range. Encouraged by the potent activity of 9a on colon cancer on the one hand and the well-known overexpression of FGFR-1 in it on the other hand, it was further selected as a representative example to be evaluated for its mechanism on the cell cycle and apoptosis of HCT116 cell line. Interestingly, 9a was found to pause the cell cycle of the HCT116 cell line at the G1 phase and induced late apoptosis. In parallel, all the synthesized hybrids 9a-p were examined for their potential to inhibit FGFR-1 at 10 µM. Compounds 9a, 9g, 9h, and 9p were found to have potent inhibitory activity with % inhibition = 63.04%, 58.31%, 60.87% and 79.84%, respectively. Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits.

Cost-effective and natural-inspired lotus root/GelMA scaffolds enhanced wound healing via ROS scavenging, angiogenesis and reepithelialization

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

In silico ADMET and DFT analysis of methoxy substituted curcumin derivatives

The current study aimed to predict drug ability of methoxy group substituted curcumin derivatives (MC1 to MC4) using ADMETLab 3.0 and DFT approaches. Almost all derivatives exhibited satisfactory physicochemical properties and medicinal chemistry. Pharmacokinetic profile revealed that all derivatives showed higher Caco-2 cell predicted permeability and exhibited a P-glycoprotein (Pgp) inhibitor capability, while non-of them is a Pgp-substrate. MC1 and MC2 exhibited favorable human intestinal absorption (HIA) values. MC1 was in favor of better oral bioavailability. Values for plasma protein binding and volume of distribution were optimum for MC1 and MC2. All compounds were unable to cross blood brain barrier. Fraction unbound in the plasma was moderate for all compounds. All derivatives exhibited moderate clearance rate, while having ultra short half-lives. Toxicity profile was moderate for almost all compounds. Similarly, the DFT computations of the compounds of the curcumin derivatives were conducted at B3LYP/6-311G** level to predict and then assess the key electronic characteristics underlying the bioactivity. Accordingly, the MC4 molecule (ΔEgap = 3.883 eV) would prefer to interact with the external molecular system more than the other molecules due to having the biggest energy gap. The ΔNmax (2.328 eV) and Δεback-donat. (−0.422 eV) scores implied that MC1 would have more charge transfer capability and the lowest stability via back donation among the compounds. In short, the derivative (MC1 to MC4) exhibited strong extrinsic therapeutic properties and therefore stand eligible for further in vitro and in vivo studies.

Discovery of in silico pharmacokinetic characteristics, drug-likeness, computational and experimental pKa values of selected unnatural fatty acid derivatives

The objective of this study was to synthesize a series of unnatural fatty acid derivatives, which have been identified as possessing distinctive properties and potential as new drug candidates. In light of the aforementioned considerations, it is imperative that the physicochemical profiles of these derivatives and their analogues be evaluated prior to the commencement of clinical trials, with a view to ascertaining their pharmacokinetic properties. In order to gain a deeper understanding of this phenomenon, a series of experimental and theoretical studies have been conducted. The pKaexp values of these derivatives were determined for the first time by potentiometric titration. These derivatives, and in particular compounds C-E, display satisfactory physicochemical properties and medicinal chemistry. As a consequence of the related prediction studies, it was observed that the molecules A1-B violated the Lipinski rule by only one criterion, whereas the compounds C-E did not violate it at all. With the exception of compounds A1-A3, compounds B-E exhibit good oral bioavailability. All compounds demonstrated acceptable toxicity profiles, although further in vivo and in vitro laboratory studies are recommended to provide more detailed insights. Furthermore, all molecules were identified as bioactive protease and enzyme inhibitors.

Synergistic Differential DNA Demethylation Activity of Danshensu (Salvia miltiorrhiza) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of Danshensu combined with probiotics (L. casei and L. acidophilus) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.

In vitro and In vivo Assessment of the Effect of Okra Gum Solid Dispersion in Atorvastatin Solubility

Background: Atorvastatin is BCS class II drug; it is lipid-lowering medication. Okra gum (OKG), from the pods of Abelmoschus esculentus, is natural product contain polymers having advantages over synthetic ones as it is safe, chemically inert, nonirritant, biodegradable, and does not require toxicological studies. Aim: This study aimed to assess the effect of okra gum solid dispersion in atorvastatin solubility. Method: The gum was extracted by hot water extraction and the dry extract was evaluated for percentage practical yield, flow properties, pH values and FTIR spectroscopy. Then solid dispersions with different drug to polymer ratios were prepared from OKG, and hydroxy propyl methyl cellulose (HPMC) by solvent evaporation method. Saturation solubility was tested for the solid dispersions prepared, the physical mixtures and atorvastatin. Tablets were prepared from solid dispersions with the highest saturation solubility, then tablets were tested and evaluated. Finally, in vivo test was done using Swiss albino mice and data were analyzed using one way Anova test followed by T test. Results: The content percent of atorvastatin in the solid dispersion prepared were 99,9- 100.1%, the tablets showed satisfactory physicochemical properties as 1.29% RSD in tablet weight variation, 24 min disintegration time, 5.24±0.457 Hardness and OKGSD tablets showed sustained release manner and 87% of drug released in 6 hrs. Lipid profile results showed significant decrease in total cholesterol level with marked decrease in LDL when using OKGSD tablets. Conclusion: It was concluded that OKG is promising excipient that can be used in dosage forms formulation to enhance solubility of low soluble drugs.

Formulation and Physicochemical Evaluation of a Herbal Dentifrice Formulated with Myristica fragrans (Nutmeg): An In Vitro Study

Aim: Dental plaque is the primary etiological factor of two of the most commonly encountered global oral health problems; dental caries and periodontal disease. The toothbrush-dentifrice combination is an essential aid in preventing them. There are several commercial chemical toothpastes available, but as of late herbal toothpastes have become more popular amongst people. Thus, the aim of this study was to formulate a novel herbal dentifrice with Myristica fragrans (Houtt.) (nutmeg), and compare its physicochemical properties with a commercially available herbal dentifrice without nutmeg. Material and method: A pilot study was conducted wherein the toothpaste was formulated under sterile conditions using various concentrations of nutmeg, tulsi leaves powder and clove powder as the main herbal ingredients. All herbal ingredients were 100% organic and certified by the Food Safety and Standard Authority of India (FSSAI). Its properties were compared and evaluated with a commercial herbal toothpaste and the most optimum formulation was then selected to be a part of the study. The properties evaluated were organoleptic parameters (colour, texture, appearance, taste, odour), pH, foamability, abrasiveness, gritty matter, homogeneity, stability and spreadability. Results: The results revealed that in comparison to the commercial herbal toothpaste, the formulated herbal toothpaste with nutmeg exhibited improved foaming ability, abrasivity, spreadability; and comparable texture, consistency, colour, gritty matter, homogeneity and stability properties. However, it had less favourable odour and taste. Conclusion: The overall results of the research provide convincing evidence of the satisfactory physicochemical properties of the nutmeg toothpaste. However, further research is warranted to test other significant properties of the toothpaste.

A comprehensive immunoinformatic analysis of chitin deacetylase’s and MP88 for designing multi-epitope vaccines against Cryptococcus neoformans

Cryptococcus neoformans causes life-threatening pneumonia and meningitis and is regarded as one of the leading killers of immunocompromised individuals. There is currently no vaccine against this pathogen. Recently, WHO placed it at the top among the critical priority groups in the fungal priority pathogens to accelerate the development of effective treatments. Numerous studies suggested the potential of subunit vaccines to overcome the challenges associated with live and inactivated whole-cell vaccines. Therefore, this study exploited integrated reverse vaccinology and immunoinformatic approach to construct and characterize multi-epitope vaccines targeting chitin deacetylases (Cda1, Cda2, Cda3) and MP88 of C. neoformans. 4 CTL, 8 HTL and 6 B cell epitopes were fused with different adjuvants and appropriate linkers to design two multi-epitope vaccines (VC1 and VC2). Both chimeric constructs were predicted to be highly antigenic, non-allergenic, non-toxic, soluble and had satisfactory physicochemical properties. Molecular docking and binding free energy calculation revealed strong binding interactions between vaccine constructs and human TLRs (TLR-2 and TLR-4). Classical MD Simulation and Normal mode analysis verified the stability of the vaccine-TLR complex in the biological environment. Codon adaptation, cloning and in silico expression suggested the efficient expression of recombinant vaccine proteins in E. coli. Both candidates also generated robust immune profiles comprising innate, adaptive and humoral immune responses. Taken together, experimental validations of our findings through extensive in vitro and in vivo testing might provide an effective vaccine for prophylactic control of C. neoformans. Communicated by Ramaswamy H. Sarma

Design, docking, MD simulation and in-silco ADMET prediction studies of novel indole-based benzamides targeting estrogen receptor alfa positive for effective breast cancer therapy

Breast cancer is one of the most common malignancies in women, afflicting millions of lives each year. Our current study suggests that the development of the most promising 7-substituted -1-(4-(piperidine-1-yl methoxy)benzyl)-1H-indole-3-carboxamide derivatives results in potent anticancer agents through in-silico investigations. The molecular docking was performed against estrogen receptor alpha (ER-α) positive (PDB ID: 3UUD) of breast cancer cells to anticipate the binding modes of the designed compounds and the likely mode of action. The interactions between the ligands and amino acid residues were thoroughly elucidated. The stability of the docked protein-ligand complexes was further confirmed by 100 ns molecular simulations methods. From in-silico studies, indole-based benzamides exhibited satisfactory physicochemical, drug-likeness and toxicity properties. To conclude, the most promising substituted benzamide analogs on the indole ring could serve as a possible modulator against ER-α positive breast cancer.

The Effect of Spray-Drying Conditions on the Characteristics of Powdered Pistacia lentiscus Leaf Extract

Pistacia lentiscus is an evergreen shrub widely used in folk medicine due to the high biological potential of the leaves’ phenolic compounds. Since phenolic compounds are susceptible to degradation under different heat, light and oxygen conditions, various microencapsulation techniques, such as spray drying, can be used to increase their stability. The objective of this study was to examine the influence of different carriers (gum arabic (GA), maltodextrin 13–17 DE (MD), β-cyclodextrin (BCD) and their mixtures), carrier concentrations in feed (12.8, 16 and 19.2% (m/V)) and drying temperatures (120, 150 and 180 °C) on the physiochemical properties, total phenolic content (TPC) and antioxidant activity (AOA) of Pistacia lentiscus leaf extract powders. Product yields of powders ranged from 23.53 to 65.51%, moisture content from 2.89 to 12.03%, hygroscopicity up to 4.45 g/100 g, solubility from 27.11 to 86.84% and bulk density from 0.24 to 0.45 g/mL. All obtained powders had satisfactory physicochemical properties, except BCD powders, which resulted in the lowest product yield, solubility and bulk density. However, BCD powders and those produced with GA containing mixtures retained the highest amounts of TPC and AOA. Thereby, the carrier mixtures with GA at a concentration of 19.2% and dried at 150 °C are recommended as the most suitable for the production of encapsulated Pistacia lentiscus leaf extracts with desirable physicochemical properties, rich in phenolics and with high antioxidant activity.

Solubility Enhancement of Atorvastatin Tablets by Solid Dispersions Using Fenugreek Seed Mucilage

Fenugreek seed mucilage (FSM) is isolated from the seeds of Trigonella Foenum-graecum, commonly known as Fenugreek, which is herbaceous plant. Fenugreek seeds contain high percentage of mucilage, which does not dissolve in water, but swell up and become slick when exposed to fluids. Atorvastatin is one of the HMG-CoA reductase inhibitors (statins), which are lipid-lowering medications used in the primary and secondary prevention of coronary heart disease. Atorvastatin is poorly absorbed orally, its oral bioavailability is very low (about14%) because it is very slightly soluble in distilled water and pH 7.4 phosphate buffer, which would limit its clinical application. The objective of this study is to enhance atorvastatin solubility in order to increase its bioavailability by the formulation of solid dispersion using fenugreek seed mucilage. Mucilage was extracted from the seed and evaluated for flow properties, pH value, FTIR spectroscopy and percentage practical yield. Then solid dispersions with different drug to polymer ratios were prepared from fenugreek mucilage and hydroxy propyl methyl cellulose (HPMC), after that saturation solubility was tested for fenugreek seed mucilage solid dispersion (FSMSD), hydroxxy propyle methyl cellulose solid dispersion (HPMCSD) and pure drug. Tablets were prepared from solid dispersion with the highest saturation solubility, then tablets were tested and evaluated. The tablets showed satisfactory physicochemical properties as 1.77%RSD in tablet weight variation, 1 min disintegration time, 5.24±0.457 Hardness and 89% drug release in 45 min. it is concluded that FSM is a promising excipient that can be used in dosage forms formulation to enhance solubility of low soluble drugs.

Biokompatibilni lipidni nanonosači za poboljšanu isporuku fluocinolonacetonida u kožu - fizičkohemijske osobine i in vitro učinak

In order to improve the delivery of topical corticosteroids into inflammatory skin lesions while reducing the likelihood of adverse effects, lipid nanocarriers have received increasing attention. Hence, this study aimed to develop biocompatible nanoemulsions (NEs) and nanostructured lipid carriers (NLCs) as carriers for fluocinolone acetonide (FA) by carefully optimizing the formulation and process parameters. After an analysis of the relevant physicochemical parameters and stability testing, in vitro release and permeation tests were performed to evaluate whether the nanocarriers affected the penetration of FA into/through the skin compared to a conventional reference product (Sinoderm® cream). The developed NEs exhibited satisfactory physicochemical properties (droplet size <200 nm, PDI<0.2, ZP>|-30| mV, pH ~ 4.75) and long-term stability. Although the developed NLCs initially had satisfactory properties, gelation was observed within 3 months of storage, implying that further formulation testing is required to resolve the limited stability of these systems. In vitro release/permeation findings suggest that the developed nanocarriers (especially NEs) provide better delivery of FA into/though the skin compared to the Sinoderm® cream. Therefore, a lecithin-based NE with a 10% lipid phase (medium-chain triglycerides/oleic acid 3:1) is a promising strategy for improved delivery of FA to the inflamed skin, allowing for ease of application, especially to larger skin surfaces and hairy regions.

Discovery of novel thioquinazoline-N-aryl-acetamide/N-arylacetohydrazide hybrids as anti-SARS-CoV-2 agents: Synthesis, in vitro biological evaluation, and molecular docking studies

In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on Mpro binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site

Preparation and characterization of sequilhos-type biscuits added with almond flour of Acrocomia intumescens.

Acrocomia intumescens (“macaúba”) is a species that during processing generates a large amount of waste. The use of this residue for the production of flour for incorporation into food products is a way to minimize the cost and nutritionally enrich the final product. This work aimed to develop and analyze, in terms of physico-chemical and microbiological properties, cookies with macaúba almond cake residual flour. Sequilhos formulations were obtained using three different proportions of flour (2, 4 and 6%). The analysis of the flour allowed to find 4.29% of moisture, 1.13% of acidity, 5.33 of pH, 44.46% of carbohydrates, 28.74% of lipids, 20.06% of proteins and 2.45% of ash. In the analysis of the sequilhos formulations, the following values were found: moisture (5.03 to 8.13%), acidity (0.10 to 0.14%), pH (5.52 to 5.93), carbohydrates (67.17 to 73.37%), lipids (18.77 to 31.77%), proteins (0.85 to 1.92%), ash (0.83 to 0.94%) and total energy value (137.57 to 172,50 Kcal/100g). In microbiological analyzes it was highlighted that the sequilhos presented adequate sanitary conditions. The results indicate almond flour as an ingredient to be incorporated in the preparation of sequilhos, which in turn, presented satisfactory physico-chemical properties and microbiological results.

Chitosan and Chitooligosaccharide: The Promising Non-Plant-Derived Prebiotics with Multiple Biological Activities.

Biodegradable chitin is the second-most abundant natural polysaccharide, widely existing in the exoskeletons of crabs, shrimps, insects, and the cell walls of fungi. Chitosan and chitooligosaccharide (COS, also named chitosan oligosaccharide) are the two most important deacetylated derivatives of chitin. Compared with chitin, chitosan and COS not only have more satisfactory physicochemical properties but also exhibit additional biological activities, which cause them to be widely applied in the fields of food, medicine, and agriculture. Additionally, due to their significant ability to improve gut microbiota, chitosan and COS are deemed prospective prebiotics. Here, we introduced the production, physicochemical properties, applications, and pharmacokinetic characteristics of chitosan and COS. Furthermore, we summarized the latest research on their antioxidant, anti-inflammatory, and antimicrobial activities. Research progress on the prebiotic functions of chitosan and COS is particularly reviewed. We creatively analyzed and discussed the mechanisms and correlations underlying these activities of chitosan and COS and their physicochemical properties. Our work enriched people’s understanding of these non-plant-derived prebiotics. Based on this review, the future directions of research on chitosan and COS are explored. Collectively, optimizing the production technology of chitin derivatives and enriching understanding of their biological functions will shed more light on their capability to improve human health.

Green synthesis of polyacrylamide grafted Neem Gum for gastro retentive floating drug delivery of Ciprofloxacin Hydrochloride: In vitro and in vivo evaluation

Gastro retentive Floating Drug Delivery Systems (GFDDS) are typically designed to enhance the efficiency of drugs; absorbed in the stomach and possess a short elimination half-life by controlling the drug release rate. This study presents, that Acrylamide Grafted Neem gum (AAm-g-NG) was synthesized for the development of tablet-based GFDDS by using the Microwave-assisted technique for the delivery of Ciprofloxacin Hydrochloride (CFX.HCL). Formulations were evaluated for pre-and post-compression studies like bulk, tapped density, angle of repose and hardness, friability, drug content, weight variation, and drug release, which satisfied all the official requirements of the tablet dosage form. The Structural characterization of the synthesized AAm-g-NG was studied by various analytical techniques like NMR, DSC, FTIR, XRD, and SEM. AAm-g-NG showed a significant swelling index, Water Retention Capacity, Waterlogged capacity, viscosity, and in vitro buoyancy compared to NG and HPMC K100 M. AAm-g-NG was also studied for hemolysis and cytotoxicity; found to be biodegradable and exhibited no toxicity in the Caco-2 cell line. The optimized batch F5 showed controlled drug release of 89% ± 3.56 at 12 h in pH 1.2 and in vivo gastric retention was approx. 8 h in rabbits. The ability of AAm-g-NG graft copolymer to extend the drug release with enhanced gastric retention is well supported by in vivo buoyancy studies and its satisfactory physicochemical properties make it a promising vehicle for gastro retentive system.

Evaluation of Physicochemical Properties, Pharmacokinetics, Biodistribution, Toxicity, and Contrast-Enhanced Cancer MRI of a Cancer-Targeting Contrast Agent, MT218.

ObjectivesPreclinical assessments were performed according to the US Food and Drug Administration guidelines to determine the physicochemical properties, pharmacokinetics, clearance, safety, and tumor-specific magnetic resonance (MR) imaging of MT218, a peptidic gadolinium-based MR imaging agent targeting to extradomain B fibronectin for MR molecular imaging of aggressive tumors.Materials and MethodsRelaxivity, chelation stability, binding affinity, safety-related target profiling, and effects on CYP450 enzymes and transporters were evaluated in vitro. Magnetic resonance imaging was performed with rats bearing prostate cancer xenografts, immunocompetent mice bearing murine pancreatic cancer allografts, and mice bearing lung cancer xenografts at different doses of MT218. Pharmacological effects on cardiovascular, respiratory, and central nervous systems were determined in rats and conscious beagle dogs. Pharmacokinetics were tested in rats and dogs. Biodistribution and excretion were studied in rats. Single and repeated dosing toxicity was evaluated in rats and dogs. In vitro and in vivo genotoxicity, in vitro hemolysis, and anaphylactic reactivity were also performed.ResultsAt 1.4 T, the r1 and r2 relaxivities of MT218 were 5.43 and 7.40 mM−1 s−1 in pure water, 6.58 and 8.87 mM−1 s−1 in phosphate-buffered saline, and 6.54 and 8.70 mM−1 s−1 in aqueous solution of human serum albumin, respectively. The binding affinity of MT218 to extradomain B fragment is 3.45 μM. MT218 exhibited no dissociation of the Gd(III) chelates under physiological conditions. The peptide degradation half-life (t1/2) of MT218 was 1.63, 5.85, and 2.63 hours in rat, dog, and human plasma, respectively. It had little effect on CYP450 enzymes and transporters. MT218 produced up to 7-fold increase of contrast-to-noise ratios in the extradomain B fibronectin–rich tumors with a dose of 0.04 mmol/kg for at least 30 minutes. MT218 had little pharmacological effect on central nervous, cardiovascular, or respiratory systems. MT218 had a mean plasma elimination half-life (t1/2) of 0.31 and 0.89 hours in rats and dogs at 0.1 mmol/kg, respectively. No detectable Gd deposition was observed in the brain at 6 hours postinjection of MT218 at 0.1 mmol/kg in rats. MT218 was not mutagenic and had no mortality or morbidity in the rats or dogs up to 1.39 and 0.70 mmol/kg/d, respectively. The no observed adverse effect level of MT218 in Sprague-Dawley rats was 1.39 mmol/kg for single dosing and 0.46 mmol/kg/d for repeated dosing. The no observed adverse effect level in dogs was 0.07 mmol/kg/d. MT218 exhibited no genotoxicity, hemolysis, and anaphylactic reactivity.ConclusionThe preclinical assessments showed that the targeted contrast agent MT218 has high r1 and r2 relaxivities, satisfactory physicochemical properties, pharmacokinetic, and safety profiles and produces effective tumor enhancement in multiple cancer types in rats and mice at reduced doses.

Activity of Propolis Nanoparticles against HSV-2: Promising Approach to Inhibiting Infection and Replication.

Herpes simplex type 2 (HSV-2) infection causes a significant life-long disease. Long-term side effects of antiviral drugs can lead to the emergence of drug resistance. Thus, propolis, a natural product derived from beehives, has been proposed to prevent or treat HSV-2 infections. Unfortunately, therapeutic applications of propolis are still limited due its poor solubility. To overcome this, a nanoparticle-based drug delivery system was employed. An ethanolic extract of propolis (EEP) was encapsulated in nanoparticles composed of poly(lactic-co-glycolic acid) and chitosan using a modified oil-in-water single emulsion by using the solvent evaporation method. The produced nanoparticles (EEP-NPs) had a spherical shape with a size of ~450 nm and presented satisfactory physicochemical properties, including positively charged surface (38.05 ± 7.65 mV), high entrapment efficiency (79.89 ± 13.92%), and sustained release profile. Moreover, EEP-NPs were less cytotoxic on Vero cells and exhibited anti-HSV-2 activity. EEP-NPs had a direct effect on the inactivation of viral particles, and also disrupted the virion entry and release from the host cells. A significant decrease in the expression levels of the HSV-2 replication-related genes (ICP4, ICP27, and gB) was also observed. Our study suggests that EEP-NPs provide a strong anti-HSV-2 activity and serve as a promising platform for the treatment of HSV-2 infections.

Development and Characterization of Transdermal patches of Tramadol Hydrochloride: An Approach to Pain Management

Transdermal drug delivery leads direct access to the systemic circulation through the skin which bypass drug from the hepatic first pass metabolism leading to increase bioavailability. Because Tramadol hydrochloride has low bioavailability, it was selected as a model drug. The present study was aimed to develop and characterize transdermal patches of Tramadol hydrochloride by solvent casting method. Two polymers Ethyl cellulose (EC) and Poly vinyl pyrrrolidine (PVP) in different combination or alone were used to form matrix system. Dibutylpthlate and Glycerine were incorporated as plasticizers. All the patches were characterized for parameters like Thickness, Weight variation, Drug content uniformity, Tensile strength, % elongation, folding endurance, moister content, In-vitro drug permeation study etc. Amongst all formulations, formulation F6 had more desirable characteristic & shows 82.82% drug permeation in 10 hr. Release kinetic can be described by Higuchi model with anomalous diffusion as a release mechanism. The Transdermal patch formulated from Ethyl Cellulose (EC) and PVP showed satisfactory physicochemical properties. So, it can be concluded that such a matrix type patches of Ethyl Cellulose (EC) and PVP could be a good carrier in transdermal delivery of Tramadol HCl. FTIR studies showed there were no incompatibilities between drug and other excipients.