Abstract
A parallel screening method has been developed to rapidly evaluate discrete library substrates of biomaterials using cell-based assays. The biomaterials used in these studies were surface-erodible polyanhydrides based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) that have been previously studied as carriers for drugs, proteins, and vaccines. Linearly varying compositional libraries of 25 different polyanhydride random copolymers (based on CPH:SA and CPTEG:CPH) were designed, fabricated, and synthesized using discrete (organic solvent-resistant) multi-sample substrates created using a novel rapid prototyping method. The combinatorial libraries were characterized at high throughput using infrared microscopy and validated using 1H NMR and size exclusion chromatography. The discrete libraries were rapidly screened for biocompatibility using standard SP2/0 myeloma, CHO and L929 fibroblasts, and J774 macrophage cell lines. At a concentration of 2.8 mg/mL, there was no appreciable cytotoxic effect on any of the four cell lines evaluated by any of the CPH:SA or CPTEG:CPH compositions. Furthermore, the activation of J774 macrophages was evaluated by incubating the cells with the polyanhydride libraries and quantifying the secreted cytokines (IL-6, IL-10, IL-12, and TNFα). The results indicated that copolymer compositions containing at least 50% CPH induced elevated amounts of TNFα. In summary, the results indicated that the methodologies described herein are amenable to the high throughput analysis of synthesized biomaterials and will facilitate the rapid and rational design of materials for use in biomedical applications.
Combinatorial Chemistry & High Throughput Screening
Title: High Throughput Cell-Based Screening of Biodegradable Polyanhydride Libraries
Volume: 12 Issue: 7
Author(s): Andrew F. Adler, Latrisha K. Petersen, Jennifer H. Wilson, Maria P. Torres, Jon B. Thorstenson, Stuart W. Gardner, Surya K. Mallapragada, Michael J. Wannemuehler and Balaji Narasimhan
Affiliation:
Abstract: A parallel screening method has been developed to rapidly evaluate discrete library substrates of biomaterials using cell-based assays. The biomaterials used in these studies were surface-erodible polyanhydrides based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) that have been previously studied as carriers for drugs, proteins, and vaccines. Linearly varying compositional libraries of 25 different polyanhydride random copolymers (based on CPH:SA and CPTEG:CPH) were designed, fabricated, and synthesized using discrete (organic solvent-resistant) multi-sample substrates created using a novel rapid prototyping method. The combinatorial libraries were characterized at high throughput using infrared microscopy and validated using 1H NMR and size exclusion chromatography. The discrete libraries were rapidly screened for biocompatibility using standard SP2/0 myeloma, CHO and L929 fibroblasts, and J774 macrophage cell lines. At a concentration of 2.8 mg/mL, there was no appreciable cytotoxic effect on any of the four cell lines evaluated by any of the CPH:SA or CPTEG:CPH compositions. Furthermore, the activation of J774 macrophages was evaluated by incubating the cells with the polyanhydride libraries and quantifying the secreted cytokines (IL-6, IL-10, IL-12, and TNFα). The results indicated that copolymer compositions containing at least 50% CPH induced elevated amounts of TNFα. In summary, the results indicated that the methodologies described herein are amenable to the high throughput analysis of synthesized biomaterials and will facilitate the rapid and rational design of materials for use in biomedical applications.
Export Options
About this article
Cite this article as:
Adler F. Andrew, Petersen K. Latrisha, Wilson H. Jennifer, Torres P. Maria, Thorstenson B. Jon, Gardner W. Stuart, Mallapragada K. Surya, Wannemuehler J. Michael and Narasimhan Balaji, High Throughput Cell-Based Screening of Biodegradable Polyanhydride Libraries, Combinatorial Chemistry & High Throughput Screening 2009; 12 (7) . https://dx.doi.org/10.2174/138620709788923764
DOI https://dx.doi.org/10.2174/138620709788923764 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Gene therapy for Multiple Myeloma
Current Gene Therapy Understanding Membrane Protein Drug Targets in Computational Perspective
Current Drug Targets Ewing’s Sarcoma Cancer Stem Cell Targeted Therapy
Current Stem Cell Research & Therapy Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Potential Clinical Use of Differentiated Cells From Embryonic or Mesencyhmal Stem Cells in Orthopaedic Problems
Current Stem Cell Research & Therapy Analysis of the Potential for HIV-1 Vpr as an Anti-Cancer Agent
Current HIV Research Dietary Assumption of Plant Polyphenols and Prevention of Allergy
Current Pharmaceutical Design The Functions of Histone Modification Enzymes in Cancer
Current Protein & Peptide Science DNA Methyltransferases Inhibitors from Natural Sources
Current Topics in Medicinal Chemistry Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response
Current Pharmaceutical Design Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Proteasome Inhibition as a New Therapeutic Principle in Hematological Malignancies
Current Drug Targets In the Crosshairs: NF-κB Targets the JNK Signaling Cascade
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Aurora-B Kinase Inhibitors for Cancer Chemotherapy
Mini-Reviews in Medicinal Chemistry Current Constructs and Targets in Clinical Development for Antibody- Based Cancer Therapy
Current Drug Targets The Extracellular Matrix Regulates Cancer Progression and Therapy Response: Implications for Prognosis and Treatment
Current Pharmaceutical Design Molecular Targets in Malignant Pleural Mesothelioma Treatment
Current Drug Targets Glioma Stem Cell Maintenance: The Role of the Microenvironment
Current Pharmaceutical Design Subject Index To Volume 6
Current Topics in Medicinal Chemistry