Nano-engineered polymers in drug delivery: Potential approaches for attenuation of secondary injury after spinal cord trauma

Wen Gao, Purdue University

Abstract

Secondary injury elicits a complex series of pathophysiological events after the primary spinal cord trauma and even after its implantation treatment for neural functional recovery. These secondary injuries include an up-regulation of glial cells associated reactive oxygen species, nitrogen species, and reactive astrogliosis, and they can result in various levels of cellular and tissue damage. The inhibition of them has been proved to lead to functional recovery of the spinal cord. In this study, we concentrated on developing polymers and nano-techniques based drug delivery strategies to eliminate these secondary injuries. To maintain and improve the performance of the implants during treatment, we exploited the polypyrrole as a suitable material to carry and locally release the drug at the injured spinal cord based on its conductive characteristics. We focused on the geometric modulation of implants materials on a nano-size scale and developed a polypyrrole nanowire platform that can served as a high capacity drug reservoir and can release drugs in a relatively longer time. Most importantly, we introduced the electromagnetic responsive feature of polypyrrole for drug delivery. This valuable technique can help us to achieve a non-invasive and remotely controlled drug release in deep tissues and avoid the physical contacts commonly required during traditional electrical stimulation. We used dexamethasone as a drug cargo, since this drug is commonly used for anti-inflammation treatment and has been successfully delivered from polypyrrole using conventional electrical stimulation methods in earlier studies. According to the results, we showed successful and long lasting polypyrrole mediated drug release under electromagnetic stimulation and the released drugs remained bioactivity and can be used for the treatment of secondary injury. We also introduced a gene silencing strategies by delivering siRNA conjugated chitosan nanoparticles to the spinal cord lesion. These siRNAs can specifically knockdown inducible nitric oxide synthase and subsequently eliminate nitric oxide induced secondary injury. This drug delivery system were designed to discriminate different macrophages which have divergent effects to spinal cord recovery and to target the specific pro-inflammatory macrophages (M1 macrophages) instead of anti-inflammatory macrophages (M2 macrophages). The targeting effect allowed us more efficiently destruct the negatively impacted mRNA in targeted cells to improve therapeutic effects after spinal cord injury.

Degree

Ph.D.

Advisors

Borgens, Purdue University.

Subject Area

Neurosciences|Nanoscience|Nanotechnology

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