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Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic

  • Mark Kester

    Mark Kester, Chief Medical Officer and co-founder of Keystone Nano, earned his PhD from the State University of New York at Buffalo. He has held faculty positions at Case Western Reserve University, Penn State University and currently serves as a Professor of Pharmacology and the Director of the NanoSTAR Institute at the University of Virginia. His research in the field of sphingolipids and nano-drug delivery systems led to the invention of the Ceramide NanoLiposome in his laboratory at Penn State University.

         , Jocelyn Bassler

    Jocelyn Bassler received her BS in Biology from Virginia Polytechnic Institute and State University and worked with Southern Research Institute for 7 years before joining Keystone Nano as a Biological Researcher. She specializes in liposome formulation development and synthesis as well as cell-based assays.

         , Todd E. Fox

    Todd E. Fox is an Assistant Professor of Pharmacology at the University of Virginia. He is the Director of the UVA Cancer Center’s Metabolomic and Lipidomic Core Facility. He is an expert in the utilization of mass spectrometry to quantify sphingolipid metabolites.

         , Carly J. Carter

    Carly J. Carter received her BS in Chemistry from Penn State University in 2003 and her PhD in Chemistry and Biochemistry from the University of Colorado in 2010. Dr. Carter’s research background includes utilizing the interactions between biological molecules and materials to develop nanoparticle therapeutics. Dr. Carter is the Research Leader at Keystone Nano.

         , Jeff A. Davidson

    Jeff A. Davidson holds a BS in Chemical Engineering from Purdue University and an MBA from the University of Minnesota. His 27 years of experience in industry and academia include serving as the Executive Director of the Penn State Bioprocessing Resource Center; founder and Executive Director of the Pennsylvania Biotechnology Association; publisher of Your World, a biotechnology applications magazine; founder of the Biotechnology Institute, a national biotechnology education nonprofit and founder of BioSciEd, Inc. Mr. Davidson co-founded Keystone Nano and has served as its CEO for the past 10 years.

         and Mylisa R. Parette

    Mylisa R. Parette received her BS in Biology and Chemistry from Towson University, a MAT degree from Brown University and her PhD in Biochemistry, Microbiology and Molecular Biology from Penn State University. Dr. Parette has served as Research Manager at Keystone Nano for the past 9 years, leading the development of NanoLiposome and calcium phosphate NanoJacket programs from the bench to IND stage.

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Published/Copyright: April 1, 2015
Biological Chemistry
From the journal Biological Chemistry Volume 396 Issue 6-7

Abstract

Despite the therapeutic potential of sphingolipids, the ability to develop this class of compounds as active pharmaceutical ingredients has been hampered by issues of solubility and delivery. Beyond these technical hurdles, significant challenges in completing the necessary preclinical studies to support regulatory review are necessary for commercialization. This review seeks to identify the obstacles and potential solutions in the translation of a novel liposomal technology from the academic bench to investigational new drug (IND) stage by discussing the preclinical development of the Ceramide NanoLiposome (CNL), which is currently being developed as an anticancer drug for the initial indication of hepatocellular carcinoma (HCC).

Keywords: ceramide; liposome; preclinical; sphingolipid; therapeutic
Corresponding author: Mylisa R. Parette, Keystone Nano, Inc, 1981 Pine Hall Road, State College, PA 16803, USA, e-mail:

About the authors

Mark Kester

Mark Kester, Chief Medical Officer and co-founder of Keystone Nano, earned his PhD from the State University of New York at Buffalo. He has held faculty positions at Case Western Reserve University, Penn State University and currently serves as a Professor of Pharmacology and the Director of the NanoSTAR Institute at the University of Virginia. His research in the field of sphingolipids and nano-drug delivery systems led to the invention of the Ceramide NanoLiposome in his laboratory at Penn State University.

Jocelyn Bassler

Jocelyn Bassler received her BS in Biology from Virginia Polytechnic Institute and State University and worked with Southern Research Institute for 7 years before joining Keystone Nano as a Biological Researcher. She specializes in liposome formulation development and synthesis as well as cell-based assays.

Todd E. Fox

Todd E. Fox is an Assistant Professor of Pharmacology at the University of Virginia. He is the Director of the UVA Cancer Center’s Metabolomic and Lipidomic Core Facility. He is an expert in the utilization of mass spectrometry to quantify sphingolipid metabolites.

Carly J. Carter

Carly J. Carter received her BS in Chemistry from Penn State University in 2003 and her PhD in Chemistry and Biochemistry from the University of Colorado in 2010. Dr. Carter’s research background includes utilizing the interactions between biological molecules and materials to develop nanoparticle therapeutics. Dr. Carter is the Research Leader at Keystone Nano.

Jeff A. Davidson

Jeff A. Davidson holds a BS in Chemical Engineering from Purdue University and an MBA from the University of Minnesota. His 27 years of experience in industry and academia include serving as the Executive Director of the Penn State Bioprocessing Resource Center; founder and Executive Director of the Pennsylvania Biotechnology Association; publisher of Your World, a biotechnology applications magazine; founder of the Biotechnology Institute, a national biotechnology education nonprofit and founder of BioSciEd, Inc. Mr. Davidson co-founded Keystone Nano and has served as its CEO for the past 10 years.

Mylisa R. Parette

Mylisa R. Parette received her BS in Biology and Chemistry from Towson University, a MAT degree from Brown University and her PhD in Biochemistry, Microbiology and Molecular Biology from Penn State University. Dr. Parette has served as Research Manager at Keystone Nano for the past 9 years, leading the development of NanoLiposome and calcium phosphate NanoJacket programs from the bench to IND stage.

Acknowledgments

The authors would like to thank Advinus LLC, Xenometrics and CERB for their evaluation of the CNL in preclinical studies. M.K. is Chief Medical Officer and co-founder of Keystone Nano, Inc. While a faculty member at Penn State University, Penn State Research Foundation licensed ceramide-based nanotechnology to Keystone Nano.

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Received: 2015-2-17
Accepted: 2015-3-21
Published Online: 2015-4-1
Published in Print: 2015-6-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: Molecular Medicine of Sphingolipids
  4. HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
  5. The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
  6. Sphingolipids in viral infection
  7. Tackling the biophysical properties of sphingolipids to decipher their biological roles
  8. Ceramide and sphingosine in pulmonary infections
  9. Molecular mechanisms of erythrocyte aging
  10. Sphingolipids in liver injury, repair and regeneration
  11. Ultrasound-stimulated microbubble enhancement of radiation response
  12. Innate immune responses in the brain of sphingolipid lysosomal storage diseases
  13. Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
  14. The role of sphingolipids in endothelial barrier function
  15. The effect of altered sphingolipid acyl chain length on various disease models
  16. Secretory sphingomyelinase in health and disease
  17. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
  18. Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
  19. The molecular medicine of acid ceramidase
  20. Caenorhabditis elegans as a model to study sphingolipid signaling
  21. S1PR4 is required for plasmacytoid dendritic cell differentiation
  22. Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
  23. Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
  24. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
  25. Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
  26. Obituary
  27. The life and work of Dr. Robert Bittman (1942–2014)
https://doi.org/10.1515/hsz-2015-0129
Keywords for this article
ceramide; liposome; preclinical; sphingolipid; therapeutic

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: Molecular Medicine of Sphingolipids
  4. HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
  5. The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
  6. Sphingolipids in viral infection
  7. Tackling the biophysical properties of sphingolipids to decipher their biological roles
  8. Ceramide and sphingosine in pulmonary infections
  9. Molecular mechanisms of erythrocyte aging
  10. Sphingolipids in liver injury, repair and regeneration
  11. Ultrasound-stimulated microbubble enhancement of radiation response
  12. Innate immune responses in the brain of sphingolipid lysosomal storage diseases
  13. Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
  14. The role of sphingolipids in endothelial barrier function
  15. The effect of altered sphingolipid acyl chain length on various disease models
  16. Secretory sphingomyelinase in health and disease
  17. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
  18. Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
  19. The molecular medicine of acid ceramidase
  20. Caenorhabditis elegans as a model to study sphingolipid signaling
  21. S1PR4 is required for plasmacytoid dendritic cell differentiation
  22. Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
  23. Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
  24. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
  25. Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
  26. Obituary
  27. The life and work of Dr. Robert Bittman (1942–2014)
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