Nanotechnology in Perinatal Medicine

About the Program

  • Provides translational nanomedicine research opportunities in Maternal-Fetal Medicine
  • Translational nanomedicine in state-of-the-art chemistry laboratories, animal facilities, and clinical settings
  • Develop an original research project with ‘bench to bedside’ implications working in a multidisciplinary environment
  • Learn to work with novel in vivo imaging agents and imaging methodologies
  • Conduct original research in the development of nanoscale therapeutics for the treatment of infection and inflammation in animal models relevant to human disease
  • Participate in journal club discussions and research seminars on new developments in the field of nanomedicine with applications in Maternal-Fetal Medicine

Objectives

  • To develop nanotechnology-based approaches for the treatment and diagnosis of disorders in Maternal-Fetal Medicine
  • To use a multi-disciplinary approach in nanomedicine research at the Perinatology Research Branch which includes physicians, engineers and scientists
  • To prepare and evaluate nanodevice formulations for the targeted therapy of maternal infection/inflammation-induced cerebral palsy

Research Questions

  • How do we deliver drugs in a targeted manner to improve efficacy and reduce side effects in the context of pregnancy?
  • What is the role of maternal intrauterine inflammation on the brain injury in the newborn?
  • Will targeted postnatal treatment of neuroinflammation lead to improved motor deficits in cerebral palsy?
  • How can we understand and characterize the in vivo effects of drugs and drug delivery nanodevices at the cellular and molecular levels?
  • What are the governing parameters for the transport of nanomaterials across the placenta?
  • How can we control and sustain the release of drugs at the targeted site for maximal therapeutic efficacy?

Important Points & Discoveries

  • Development of a unique pregnant rabbit model of maternal inflammation-induced cerebral palsy in the fetus characterized by neurobehavioral assessment, PET/MRI imaging, and tissue/mRNA analysis
  • Development of dendrimer-based capture assays for the detection of cytokine levels with a 20-fold improvement in sensitivity
  • Polyamidoamine (PAMAM) dendrimers can target targeted cells associated with neuroinflammation, even upon intravenous administration
  • Systemic, post-natal administration of dendrimer-based drug delivery nanodevices can attenuate neuroinflammation and improve motor deficits in newborn rabbits kits with cerebral palsy

Selected Publications

  • Kannan S, Saadani-Makki F, Muzik O, Chakraborty P, Mangner TJ, Janisse J, Romero R, Chugani DC. Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med 2007 Jun;48(6):946-54.
  • Saadani-Makki F, Kannan S, Lu X, Janisse J, Dawe E, Edwin S, Romero R, Chugani D. Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy. Am J Obstet Gynecol 2008 Dec;199:651.e1-7.
  • Kurtoglu YE, Navath RS, Wang B, Kannan S, Romero R, Kannan RM. Poly(amidoamine) dendrimer-drug conjugates with disulfide linkages for intracellular drug delivery. Biomaterials 2009 Apr;30:2112-21.
  • Menjoge AR, Rinderknecht AL, Navath RS, Faridnia M, Kim CJ, Romero R, Miller RK, Kannan RM. Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy. J Control Release. 2011 Mar;150:326-38.
  • Dai H, Navath RS, Balakrishnan B, Guru BR, Mishra MK, Romero R, Kannan RM, Kannan S. Intrinsic targeting of inflammatory cells in the brain by polyamidoamine dendrimers upon subarachnoid administration. Nanomedicine (Lond) 2010 Nov;5:1317-29.
  • Kannan S, Saadani-Makki F, Balakrishnan B, Dai H, Chakraborty PK, Janisse J, Muzik O, Romero R, Chugani DC. Decreased cortical serotonin in neonatal rabbits exposed to endotoxin in utero. J Cereb Blood Flow Metab 2011 Feb;31:738-49.

Distinguished Faculty

 

DIRECTOR
Rangaramanujam M. Kannan, M.D.

Professor, Department of Chemical Engineering and Material Science, Biomedical Engineering, Wayne State University

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