Ocular Microemulsion of Brinzolamide: Formulation, Physicochemical Characterization, and in vitro Irritation Studies based on EpiOcular™ Eye Irritation Assay

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

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Development and physicochemical characterization of novel porous phosphate glass bone graft substitute and in vitro comparison with xenograft

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-021-06532-8 ◽

2021 ◽

Vol 32 (6) ◽

Author(s):

Niketa Chauhan ◽

Nilay Lakhkar ◽

Amol Chaudhari

Keyword(s):

Cell Proliferation ◽

Physicochemical Properties ◽

Bone Graft ◽

Phosphate Glass ◽

Physicochemical Characterization ◽

Bone Graft Substitute ◽

Organic Content ◽

In Vitro Cytotoxicity ◽

Porous Phosphate

AbstractThe process of bone regeneration in bone grafting procedures is greatly influenced by the physicochemical properties of the bone graft substitute. In this study, porous phosphate glass (PPG) morsels were developed and their physicochemical properties such as degradation, crystallinity, organic content, surface topography, particle size and porosity were evaluated using various analytical methods. The in vitro cytotoxicity of the PPG morsels was assessed and the interaction of the PPG morsels with Dental Pulp Stem Cells (DPSCs) was studied by measuring cell proliferation and cell penetration depth. The cell-material interactions between PPG morsels and a commercially available xenograft (XG) were compared. The PPG morsels were observed to be amorphous, biocompatible and highly porous (porosity = 58.45%). From in vitro experiments, PPG morsels were observed to be non-cytotoxic and showed better cell proliferation. The internal surface of PPG was easily accessible to the cells compared to XG.

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State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

Toxicology Research and Application ◽

10.1177/2397847320979751 ◽

2020 ◽

Vol 4 ◽

pp. 239784732097975

Author(s):

Stéphanie Boué ◽

Didier Goedertier ◽

Julia Hoeng ◽

Anita Iskandar ◽

Arkadiusz K Kuczaj ◽

...

Keyword(s):

Ad Hoc ◽

State Of The Art ◽

Physicochemical Characterization ◽

Objective Evaluation ◽

Vapor Generation ◽

Characterization Methods ◽

Clinical Exposure ◽

Aerosol Generation

E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.

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Potential of Probiotic Frozen Blackcurrant Products: Consumer Preference, Physicochemical Characterization, and Cell Viability

Foods ◽

10.3390/foods10040792 ◽

2021 ◽

Vol 10 (4) ◽

pp. 792

Author(s):

Kati Väkeväinen ◽

Noora Rinkinen ◽

Roosa-Maria Willman ◽

Jenni Lappi ◽

Kaisa Raninen ◽

...

Keyword(s):

Storage Time ◽

Physicochemical Characterization ◽

Consumer Preference ◽

Nutritional Composition ◽

Point Of View ◽

Raw Material ◽

Frozen Food ◽

High Viability ◽

Food Applications

Blackcurrant is a healthy, affordable, and traditionally gardened berry that, thus far, has been underused in food applications. From the consumers’ point of view, the acidic taste of blackcurrants is a challenge; therefore, these berries have mainly been utilized for sugary juice production. This research study aimed to develop a frozen vegan blackcurrant product with pleasant sensory properties and potential probiotic function. A candidate probiotic, Lactoplantibacillus plantarum Q823, was used in the manufacturing process. The physicochemical properties, nutritional composition, and consumer preference for the developed product were assessed, as was the viability of L. plantarum Q823 during storage time and in an in vitro gastrointestinal model. Consumers (n = 71) perceived the developed product to be pleasant. L. plantarum Q823 had high viability counts (log colony forming units (cfu) g−1 7.0 ± 0.38) in the final product, although the viability of L. plantarum Q823 during storage time needs to be enhanced to obtain a probiotic product. Thus, within an optimized formulation, blackcurrant berries represent a potential raw material for functional frozen food products.

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Physicochemical characterization and in vitro antioxidant activity of hyaluronic acid produced by Streptococcus zooepidemicus CCT 7546

Preparative Biochemistry & Biotechnology ◽

10.1080/10826068.2021.1929320 ◽

2021 ◽

pp. 1-10

Author(s):

Wilza Kímilly Vital de Paiva ◽

Waleska Rayane Dantas Bezerra de Medeiros ◽

Cristiane Fernandes de Assis ◽

Everaldo Silvino dos Santos ◽

Francisco Caninde de Sousa Júnior

Keyword(s):

Antioxidant Activity ◽

Hyaluronic Acid ◽

Physicochemical Characterization ◽

Streptococcus Zooepidemicus ◽

In Vitro Antioxidant Activity

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Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

Alternatives to Laboratory Animals ◽

10.1177/026119299202000120 ◽

1992 ◽

Vol 20 (1) ◽

pp. 146-163

Author(s):

Francis H. Kruszewski ◽

Laura H. Hearn ◽

Kyle T. Smith ◽

Janice J. Teal ◽

Virginia C. Gordon ◽

...

Keyword(s):

Double Blind ◽

Eye Irritation ◽

Ocular Irritation ◽

Rabbit Eye ◽

Wide Range ◽

High Concentrations ◽

Alkaline Membrane ◽

Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

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Physicochemical Characterization and Functional Potential of Phaseolus vulgaris L. and Phaseolus coccineus L. Landrace Green Beans

Agronomy ◽

10.3390/agronomy11040803 ◽

2021 ◽

Vol 11 (4) ◽

pp. 803

Author(s):

Elia Nora Aquino-Bolaños ◽

Alma Karina Garzón-García ◽

Jimena Esther Alba-Jiménez ◽

José Luis Chávez-Servia ◽

Araceli Minerva Vera-Guzmán ◽

...

Keyword(s):

Antioxidant Activity ◽

Physicochemical Characterization ◽

Titratable Acidity ◽

Soluble Solids ◽

Total Phenolic ◽

Green Beans ◽

Total Sugars ◽

Total Soluble Solids ◽

Color Parameters

The green bean is an important crop worldwide, because it is rich in protein, dietary fiber, vitamins, and minerals, as well as bioactive compounds that provide it with important functional properties; however, the composition of many landraces is still unknown. The purpose of this project was to characterize Phaselus vulgaris and coccineus L. landrace green beans on pH, titratable acidity, total soluble solids, total sugars, color parameters, total phenols, monomeric anthocyanins, and in vitro antioxidant activity (DPPH and FRAP). Regarding the content of total sugars, differences were registered between both species, as opposed to results observed in total soluble solids. Color parameters showed higher reddish tones for P. vulgaris landraces, though P. coccineus had a higher total phenolic content, especially the reddish landraces, which correlated directly to a higher antioxidant activity by DPPH and FRAP. In the protein content, the species P. vulgaris registered the highest content. These results could contribute to a greater use and even promote the genetic improvement of the outstanding pods that serve as one of the main food products in rural regions for higher benefits.

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Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

Molecules ◽

10.3390/molecules26144127 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4127

Author(s):

Aline de Cristo Soares Alves ◽

Franciele Aline Bruinsmann ◽

Silvia Stanisçuaski Guterres ◽

Adriana Raffin Pohlmann

Keyword(s):

Monoclonal Antibody ◽

Physicochemical Characterization ◽

Vascular Endothelial ◽

Organic Nanoparticles ◽

Humanized Monoclonal Antibody ◽

Angiogenesis Process ◽

Endothelial Growth Factor ◽

Drug Pharmacokinetics

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

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The EYTEX™ System and the Neutral Red Uptake Inhibition Assay in Cultured Hep G2 Cells as Alternative Methods for In Vivo Eye Irritation Following the EEC Protocol

Alternatives to Laboratory Animals ◽

10.1177/026119299001700406 ◽

1990 ◽

Vol 17 (4) ◽

pp. 325-333

Author(s):

Paul J. Dierickx ◽

Virginia C. Gordon

Keyword(s):

Neutral Red ◽

Alternative Methods ◽

Inhibition Assay ◽

Hep G2 ◽

Hep G2 Cells ◽

Eye Irritation ◽

Uptake Inhibition ◽

In Vitro Methods ◽

Neutral Red Uptake

The neutral red uptake inhibition assay and the EYTEX™ system were investigated as alternative methods for the assessment of eye irritation, determined according to the EEC protocol. The 17 test chemicals used were mainly organic solvents. The xenobiotics were applied to Hep G2 cells for 24 hours at different concentrations. Neutral red uptake inhibition was then measured. The results are expressed as the NI50 value, which is the concentration of test compound required to induce a 50% reduction in neutral red uptake. The same chemicals were also tested as coded samples by the EYTEX™ test according to the manufacturer's directions. A nearly identical quantitative correlation was found for both in vitro methods with corneal opacity scores: r = 0.84 for EYTEX™ scores and r = 0.83 for log NI50, expressed in μg/ml. Whilst these correlations are certainly not perfect, it is clear that both in vitro methods can be used as valuable prescreening methods.

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Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation

Nanomaterials ◽

10.3390/nano11010152 ◽

2021 ◽

Vol 11 (1) ◽

pp. 152

Author(s):

Iulia Pinzaru ◽

Cristian Sarau ◽

Dorina Coricovac ◽

Iasmina Marcovici ◽

Crinela Utescu ◽

...

Keyword(s):

Antitumor Activity ◽

Betulinic Acid ◽

Water Solubility ◽

Physicochemical Characterization ◽

A549 Cells ◽

Drug Carriers ◽

Biological Evaluation ◽

Correlation Spectroscopy ◽

Hydrodynamic Diameter

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models—hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

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