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Model Driven Optimization of Drug Delivery for Spinal Cord Injury
Start Date: 6/7/2017Start Time: 3:30 PM
End Date: 6/7/2017End Time: 5:30 PM

Event Description
BIOMED Master's Thesis Defense

Title:
Model Driven Optimization of Drug Delivery for Spinal Cord Injury

Speaker:
Neil Mittal, MS Candidate, School of Biomedical Engineering, Science and Health Systems

Advisor:
Yinghui Zhong, PhD, Assistant Professor, School of Biomedical Engineering, Science and Health Systems

Abstract:
Spinal cord injuries have an annual new case incidence in the United States of up to 40 cases per million population, with a 36.2% 10 year survival rate in patients over 50 years old. Barely half of survivors from 40 to 60 can perform activities of daily living, regardless of the severity of the initial injury. (Devivo, 2012) Spinal cord injury is progressive, mediated by secondary injury, or a subacute inflammatory process that is poorly understood. (Biyani & El Masry, 1994; Guizar-Sahagun et al., 1994; Oyinbo, 2011) Secondary injury can involve or lead to apoptosis, scarring, cavitation, ischemia, and demyelination, among other sequelae, and many of these are not conducive to neuronal recovery. (Oyinbo, 2011) Therefore there is a need for improved ways of addressing secondary injury mechanisms in these patients. (Biyani & El Masry, 1994)

Minocycline can target multiple secondary injury mechanisms through its anti-inflammatory, anti-oxidative, and anti-apoptotic effects. (Freeman, Nightingale, & Quintiliani, 1994; Plane, Shen, Pleasure, & Deng, 2010; Wells, Hurlbert, Fehlings, & Yong, 2003) However, it is only fully effective at high concentrations. At the systemic levels required for this, minocycline can cause liver toxicity and even death. (Zhang et al., 2015) Minocycline can form self-assembling, water insoluble particles with dextran sulfate and divalent metal cations, with high entrapment efficiency and a stable, slow release. There is potential for a controllable vehicle for drug delivery to optimize dosing with minocycline. (Zhang et al., 2015)

Predicting minocycline release behavior of a complex system can be performed by the creation of a model to simplify the system to an equation. This simplification can be guided by a combination of theoretical frameworks and previous empirical data that suggests idealized ratios between the components; previous work suggests the highest entrapment efficiency given a 1:1.2 mass concentration ratio of minocycline: dextran sulfate, in the presence of 7.2 mM Mg2+, suggesting saturation of binding sites at these values. (Zhang et al., 2015) With a high degree of accuracy, this model can help direct the optimization of the drug delivery system. In the case of minocycline: dextran sulfate: Mg2+, the model proposed in this study was able to predict the trend of behavior but not with enough sensitivity for small dosing changes that characterize this delivery method.

Biomedical engineering is an interdisciplinary field that combines understanding of various scientific and design expertise. In order to tailor a drug delivery system, as well as help to characterize the mechanism of release, generating a simple model can provide insight to the behavior of the system while reducing time, labor, and cost.
Contact Information:
Name: Ken Barbee
Phone: 215-895-1335
Email: barbee@drexel.edu
Neil Mittal
Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets.
Audience:
  • Undergraduate Students
  • Graduate Students
  • Faculty
  • Staff

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