News Article | January 10, 2017
MORGANTOWN, W.Va., Jan. 10, 2017 (GLOBE NEWSWIRE) -- Protea Biosciences Group, Inc. (OTCQB:PRGB) (“Protea”) announced today that the Company has entered into a co-marketing agreement with MatTek Corporation (“MatTek”), which allows Protea to include MatTek’s human cell based in vitro tissue models with Protea’s proprietary molecular imaging services. “By combining the human tissue models with mass spectrometry imaging workflows, researchers will be able to visualize specific compounds in highly - controlled experimental conditions using human cell derived, in vitro models,” stated Haddon Goodman, Vice President, Corporate Development. He added, “For example, utilizing MatTek’s EpiDerm™ skin model, we can map the distribution of topical compounds, while also visualizing the distribution of biomolecules present in the tissue. These experiments determine if a compound is penetrating the skin without using a tag or marker on the compound, which are commonly needed for visualization using traditional techniques.” The in vitro models are easier to source, much more reproducible and more humane as compared to human or animal skin tissues. MatTek is at the forefront of tissue engineering and is a world leader in the production of innovative 3D reconstructed human tissue models. The outstanding relevance and reproducibility of EpiDerm and EpiOcular, MatTek’s corneal tissue model, produced impressive results in international multi-laboratory pre-validation and validation studies, leading to acceptance by OECD as test methods for skin and ocular irritation and corrosion testing. The companies plan to jointly present data at the 76th annual Society for Investigative Dermatology conference on April 26-29 in Portland, Oregon. This work will highlight the benefit of integrating human cell-based tissue models with Protea’s mass spectrometry imaging workflows. About Protea Biosciences Group, Inc.: Protea Biosciences Group, Inc. (OTCQB:PRGB) is a molecular information company providing proprietary, bioanalytical workflows to the pharmaceutical and life science industries. "Molecular information", the generation and bioinformatic processing of very large data sets, is obtained by applying the Company's technology to identify and characterize the proteins, metabolites, lipids and other biologically-active molecules which are the byproducts of all living cells and life forms. About MatTek Corporation: MatTek Corporation is at the forefront of tissue engineering and is a world leader in the production of innovative 3D reconstructed human tissue models. MatTek’s skin, ocular, intestinal and respiratory tissue models are used in regulatory toxicology (OECD, EU guidelines) and product development programs to address toxicology and efficacy concerns throughout the cosmetic/personal care, household product, chemical, and pharmaceutical industries. Forward-Looking Statements; This press release may contain statements relating to future results or events, which are forward-looking statements. Words such as "expects", "intends", "plans", "may", "could", "should", "anticipates", "likely", "believes" and words of similar import may identify forward-looking statements. These statements are not historical facts, but instead represent only the Company's belief regarding future events, many of which, by their nature, are inherently uncertain and outside of the Company's control. It is possible that the Company's actual results and financial condition may differ, possibly materially, from the anticipated results and financial condition indicated in these forward-looking statements. Further, information concerning the Company and its business, including factors that potentially could materially affect the Company's business and financial and other results, are contained in the Company's filings with the Securities and Exchange Commission, available at www.sec.gov. All forward-looking statements included in this press release are made only as of the date of this press release, and we do not undertake any obligation to publicly update or correct any forward-looking statements to reflect events or circumstances that subsequently occur or of which we hereafter become aware. Protea and LAESI are registered trademarks of Protea Biosciences Group, Inc.
Desai P.R.,Florida A&M University |
Shah P.P.,Florida A&M University |
Hayden P.,Mattek Corporation |
Singh M.,Florida A&M University
Pharmaceutical Research | Year: 2013
Purpose: To investigate the percutaneous permeation pathways of cell penetrating peptide modified lipid nanoparticles and oleic acid modified polymeric nanoparticles. Methods: Confocal microscopy was performed on skin cultures (EpiDermFT™) for modified and un-modified nanoparticles. Differential stripping was performed following in vitro skin permeation of Ibuprofen (Ibu) encapsulated nanoparticles to estimate Ibu levels in different skin layers and receiver compartment. The hair follicles (HF) were blocked and in vitro skin permeation of nanoparticles was then compared with unblocked HF. The surface modified nanoparticles were investigated for response on allergic contact dermatitis (ACD). Results: Surface modified nanoparticles showed a significant higher (p < 0.05) in fluorescence in EpiDermFT™ cultures compared to controls. The HF play less than 5% role in total nanoparticle permeation into the skin. The Ibu levels were significantly high (p < 0.05) for surface modified nanoparticles compared to controls. The Ibu levels in skin and receiver compartment were not significantly different when HF were open or closed. Modified nanoparticles showed significant improvement in treatment of ACD compared to solution. Conclusions: Our studies demonstrate that increased skin permeation of surface modified nanoparticles is not only dependent on a follicular pathway but also occur through non-follicular pathway(s). © 2012 Springer Science+Business Media New York.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 835.98K | Year: 2011
DESCRIPTION (provided by applicant): Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. Recently enacted legislation including the European Union (EU) Registration, Labeling and Authorization of Chemicals (REACH) program, and the US EPA High production Volume (HPV) Chemical Challenge will dramatically increase the need for inhalation toxicity information. The goal of the present grant proposal is to validate the EpiAirway in vitro human airway model for prediction of in vivo human inhalation toxicity hazard potential following Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Center for Validation of Alternative Methods (ECVAM) guidelines. Phase I experiments produced several prediction models that will be further tested in the current Phase II project. One hundred chemicals that have available in vivo human or animal inhalation toxicity data and established immediately Dangerous to Life or health (IDLH) concentrations established by NIOSH will be utilized in the Phase II validation project. Interlaboratory transferability of the method will also be evaluated in 4 laboratories using a subset of 30 chemicals chosen from the original 100 tested during the Phase II study. The study data will then be submitted for independent statistical analysis and the final results and report will be submitted to regulatory agencies (i.e. ICCVAM) in support of regulatory acceptance. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and a technical capacity thatis urgently needed but that does not presently exist. The methodology developed will provide a transformative technology that will facilitate the paradigm shift from in vivo rodent to in vitro human inhalation toxicology testing envisioned in the resent National Research Council Report Toxicity Testing in the 21st Century: A Vision and a Strategy . PUBLIC HEALTH RELEVANCE: Hazard assessment, including evaluation of acute inhalation toxicity potential, is a mandatory international regulatory requirement for chemicals utilized in international commerce. Acute inhalation toxicity or irritation potential is an important consideration in establishing procedures for the safe handling, packaging and labeling and transport of chemicals and chemical mixtures, and in formulating responses to emergency exposure situations. The technology to be validated in the current Phase II proposal will address a critical barrier to implementation of worldwide requirements for inhalation toxicity testing of chemicals, and provide a technical capability that is urgently needed but that does not presently exist.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 993.51K | Year: 2011
DESCRIPTION (provided by applicant): Environmental or occupational exposure to a broad variety of chemical agents can alter normal endocrine function. The effects of these endocrine disruptors (ED) can have serious health implications including deleterious effects to reproductive capacity, fetal development, the immune system, and carcinogenesis. Current animal tests are expensive, use a large number of animals, and are not necessarily applicable to humans. Thus, a validated, human in vitro method to identify ED is an area of great importance. This research project will validate an organotypic EpiVaginal tissue model for Tier 1 screening of chemicals with endocrine disrupting potential. Phase I research will validate MatTek's organotypic vaginal-ectocervical (EpiVaginalTM) tissue model for use in identifying ED. A battery of 75 model compounds with known ED activity will be selected from the revised ICCVAM list of recommended substances. The production of estrone by the tissue model and changes to tissue morphology and gene expression will be monitored as biomarkers of ED. A prediction model for ED with be finalized and the test method will undergo formal validation in a multi-center, GLP study. In addition, reproducibility of the assay method and adaptation of the method to a high throughput screen format will be investigated. If successful, the proposed method will have high impact in environmental chemical safety programs and ultimately will reduce the effect of these chemicals on human health. PUBLIC HEALTH RELEVANCE: Validation an in vitro organotypic tissue based assay to screen for endocrine disrupting potential is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The assaymethod will be adapted to a high throughput format to allow rapid and low- cost screening of chemicals. The organotypic tissue based in vitro screening method will have enormous environmental and public health significance.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 924.52K | Year: 2011
DESCRIPTION (provided by applicant): Replacement of the Draize rabbit eye test for ocular irritancy testing remains an elusive goal. Many believe a corneal full thickness (CFT) model is necessary to completely model the interaction of exogenous chemicals with human cornea. During Phase 1, human corneal epithelial, stromal, and endothelial cells were isolated from native tissue, expanded in monolayer culture, and cryopreserved. Culture conditions were identified to produce highly differentiated 2-layer (corneal epithelium and keratocyte-containing stroma) and 3- layer (epithelium, stroma, and endothelium) CFT tissues. The CFT tissues exhibited improvements over epithelial tissues in terms of barrier and differentiated phenotype. An assay and prediction model(PM) was developed which allowed the CFT tissue to distinguish between irritants and non-irritants with 100% accuracy. Other functional studies showed that the CFT tissue appears suitable to evaluate time to recovery (TTR) and depth of injury (DOI) following chemical injury. Finally, an analysis of CFT tissue production showed that the economics of CFT are favorable. Phase II will expand upon the Phase 1 result to further develop the CFT tissue model. Initial goals will focus on preparing the CFT tissue model for commercial production - cell stocks will be expanded to insure a stable cell supply and quality control parameters will be developed. The database of materials tested using the CFT will be expanded, the PM for irritant/non-irritant classification will be finalized, and inter-laboratory transferability of the assay will be demonstrated. Finally, the CFT tissues will be used for TTR and DOI measurements and an assay and prediction model for replacement of the Draize test will be developed. Due to theseenhanced capabilities, the CFT will provide toxicologists and scientists with a tool that will dramatically decrease, if not entirely eliminate, the need for animal testing to determine ocular irritancy. PUBLIC HEALTH RELEVANCE: Safety assessment of all new chemicals and products requires evaluation of potential ocular irritancy in case of intentional or unintentional exposure to the eye. Current animal-based test methods are suboptimal because of animal welfare concerns and in vitro methods lack the complexity required to completely model in vivo responses. We will develop a corneal full thickness tissue and in vitro test methods that will dramatically reduce or eliminate the need to use animals to assess ocular irritancy of chemicals and products.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 966.45K | Year: 2012
DESCRIPTION (provided by applicant): The goal of the current proposal is to apply state-of-the-art gene modification technology, including lentiviral delivery systems and RNA interference (RNAi) technology, to produce commercially available tissue engineered in vitro human models with advanced functional features. The commercial products to be developed will consist of organotypic 3-D skin and airway epithelial models that will be utilized for toxicology testing in consumer product/drug development, immunology and basic research applications. Advanced features that will be incorporated into the genetically modified tissue engineered in vitro human models will include: 1) gene activity reporter functions for monitoring the activity of various cel signaling pathways of toxicological, immunological or developmental significance; and 2) genetically modified tissue engineered in vitro human models with knockdown or over-expression of specific genetic functions. During the Phase I project, the feasibility of producing these models was established by development of organotypic skin and airway models with reporter functions for monitoring activity of NF B and Nrf2 transcription factors (TFs). These TFs are involved in inflammatory and antioxidant response signalingpathways, respectively. Induction of reporter activity was evaluated qualitatively by epifluorescence microscopy of green fluorescent protein (GFP), and quantitatively by measurement of luciferase activity in tissue extracts. Significant progress was alsomade in development of gene knockdown models. Epidermal cells were genetically modified to allow inducible knockdown of interleukin-1 IL-1 , a cytokine that plays an important role in epithelial inflammation, wound healing and disease states induced by environmental agents. Knockdown of IL-1 gene and protein expression of 72 % was achieved. Incorporation of these cells into organotypic models and further functional testing is in progress. A panel of 14 organotypic skin and airway epithelial TF reporter models for monitoring activity of cell signaling pathways of toxicological, immunological or developmental significance will be produced during the Phase II project. The models will be assembled into commercial products consisting of various combinations andconfigurations including high throughput 96-well formats, and validated with a comprehensive set of reference chemicals. These models will allow mechanistic toxicological evaluation of industrial chemicals, consumer product ingredients or environmental agents. The commercial models are intended for use by chemical producers, consumer product and cosmetic manufacturers, pharmaceutical companies, as well as industrial, governmental and academic environmental toxicologists and pharmaceutical researchers.PUBLIC HEALTH RELEVANCE: The organotypic in vitro human models produced by the project will allow mechanistic toxicological evaluation of industrial chemicals, consumer product ingredients or environmental agents for the protection of public health. These commercial models are intended for use by chemical producers, consumer product and cosmetic manufacturers, pharmaceutical companies, as well as industrial, governmental and academic environmental toxicologists and pharmaceutical researchers.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 218.33K | Year: 2014
DESCRIPTION (provided by applicant): The perioral route for drug administration remains the most convenient way of clinical therapy and is preferred by patients, however, good bioavailability is a necessary characteristic of new candidate therapeutics. A key parameter for determining oral bioavailability is drug transport and permeability across the small intestine (SI) epithelium. Therefore, in vitro models of SI epithelium that accurately predict in vivo human transport/permeability of candidate drugs are of high interest to the pharmaceutical industry. Currently available in vitro models have significant deficiencies which limit their utility for dru development applications, including poor correlation to in vivo human carrier-mediated transport and parcellular permeation, as well as a lack of in vivo human small intestine metabolic enzyme activity. The current proposal aims to develop an in vitro human SI for use in pharmaceutical development applications. The SI model will consist of primary huma
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 267.91K | Year: 2010
DESCRIPTION (provided by applicant): Due to the avoidance of first-pass hepatic metabolism and gastrointestinal irritation, intravaginal administration is an attractive option for systemic delivery of drugs. Current vaginal drug delivery studies are primarily performed using the FDA-accepted rabbit model. However, such studies are costly and time consuming. In addition, animal experiments are often highly variable. To avoid these problems, we propose use of a highly differentiated and reproducible, in vitro reconstructed human vaginal ectocervical (VEC) tissue model such as MatTek EpiVaginalTM model. However, the barrier properties of the EpiVaginal model need to be optimized so that they accurately match those of native in vivo tissue. . Phase Iresearch will produce various EpiVaginal cultures in which the tissue phenotype has been modified. These tissues will be characterized in terms of histology, barrier properties (measured by transepithelial electrical resistance), and the presence of organelles important in determining mucosal barrier properties such as desmosomes and tight junctions. In addition, the levels of barrier lipids will be quantified. The most promising tissues will be selected for drug permeability studies using a set of model drugs for which historical pharmacokinetic intravaginal rabbit data are available. The in vitro and in vivo data will be compared to choose the tissue with optimized barrier properties. Finally, the economics of utilizing the in vitro tissue model for pre-clinical intravaginal drug delivery studies versus rabbit studies will be compared. PUBLIC HEALTH RELEVANCE: The vaginal route has a great potential for systemic drug delivery due to its large surface area, high vascularization, permeability to a wide range of compounds including peptides and proteins, and avoidance of the hepatic first-pass metabolism and gastrointestinal irritation. Since drug absorption potential has become important criterion for decisions early in the drug discovery process, there is a great need to develop a reliable screening method for drug adsorption through the vaginal route. This proposal will optimize a highly differentiated, human vaginal tissue model to facilitate such studies.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 648.82K | Year: 2016
DESCRIPTION provided by applicant Approximately of currently marketed drugs are orally administered formulations whose clinical efficacy critically depends on the absorption from the small intestine SMI However currently available in vitro intestinal models rely predominantly on cancer cell lines that do not recapitulate the D microenvironment of the small intestine Likewise animal models often fail short in predicting in vivo human outcomes of candidate drugs During Phase I we successfully developed a promising small intestine drug permeation model based on an in vitro organotypic tissue comprised of human SMI cells Characterization of the in vitro SMI tissues showed good correspondence to native human tissue in terms of histology transepithelial electrical resistance and structural features The utility of the SMI model for drug permeation studies was demonstrated In vitro SMI permeability data strongly correlated with in vivo human absorption data r whereas data from the widely used Caco cell line model was less predictive r Permeability data also demonstrated that efflux transporters were functional in the SMI in vitro tissue and inhibition studies showed that the SMI tissue will likely be useful to study drug drug interactions An economic analysis of the in vitro model showed significant advantages versus comparable rodent bioavailability studies The ultimate goal of this project is produce a validated biologically relevant organotypic SMI model that predicts intestinal drug absorption bioavailability of orally administered drugs The human in vivo like characteristics of the SMI model and its capacity to measure drug absorption metabolism and drug drug interactions make it a superior tool to existing in vitro and ex vivo methods In the proposed application we will finalize a drug permeation and metabolism prediction model Reproducibility of the model will be determined and transferability of the in vitro assay methods to other laboratories will be demonstrated Successful completion of these Phase goals will result in an extremely useful model for early preclinical drug screening The human primary cell based SMI tissue model will improve pharmacokinetic analysis of new drug formulations accelerate drug development and reduce the ever increasing development cost of drugs PUBLIC HEALTH RELEVANCE Current animal and in vitro cell culture models often fail to predict human responses for drug permeation metabolism and drug drug interactions in the small intestine SMI This project will validate an in vitro human primary cell based SMI assay system to accurately predict drug bioavailability and disposition of orally administered drugs The model will provide a transformative platform to facilitate permeability metabolism and drug induced interplay between drug transporters and metabolic enzymes in the SMI The new model will serve as an important preclinical screening tool for drug candidates that are designed to cross the gastrointestinal mucosal epithelium
Mattek Corporation | Date: 2016-11-22
Cells, tissue models, cell growth media, and biomaterials for use in biological, biomedical, and life sciences research.