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
-
The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target
Current Cancer Drug Targets Changes in Glutathione, Oxidative Stress and Mitochondrial Membrane Potential in Apoptosis Involving the Anticancer Activity of Cantharidin Isolated from Redheaded Blister Beetles, Epicauta hirticornis
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Health Promoting Effect of Dietary Polyphenols
Current Nutrition & Food Science Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology
Recent Patents on Anti-Cancer Drug Discovery Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?
Current Cancer Drug Targets Drug Repositioning for the Treatment of Hematologic Disease: Limits, Challenges and Future Perspectives
Current Medicinal Chemistry Curcumin: the Yellow Molecule with Pleiotropic Biological Effects
Letters in Drug Design & Discovery Recent Patents on Live Bacteria and their Products as Potential Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies
Current Drug Delivery Biomarkers and Osteosarcoma and IGF
Recent Patents on Biomarkers Fyn Kinase in Brain Diseases and Cancer: The Search for Inhibitors
Current Medicinal Chemistry Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy
Current Cancer Drug Targets Antisense Oligonucleotides as an Innovative Therapeutic Strategy in the Treatment of High-Grade Gliomas
Recent Patents on CNS Drug Discovery (Discontinued) Stem Cell Transplantation for Hematological Malignancies: Prospects for Personalized Medicine and Co-therapy with Mesenchymal Stem Cells
Current Pharmacogenomics and Personalized Medicine Natural Products and Cancer Stem Cells
Current Pharmaceutical Design Detection of Damaging nsSNPs on Human Caspase-Cascades Related to Apoptotic Signalling Pathway
Protein & Peptide Letters Phenotypic Alteration of Bone Marrow HSC and Microenvironmental Association in Experimentally Induced Leukemia
Current Stem Cell Research & Therapy Membrane Tyrosine Kinase Receptors are an Important Target for the Therapy of Acute Myeloid Leukemia
Current Cancer Therapy Reviews An Unusual Presentation of a Rare Scleroderma Mimic: What is Behind the Scenes?
Current Rheumatology Reviews Anticancer Therapeutic Strategies Based on CDK Inhibitors
Current Pharmaceutical Design