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Preparation and characterization of poly (ester amine) derivative | 47917

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Preparation and characterization of poly (ester amine) derivatives for lungcancer gene therapy

International Conference on Central Nervous System - Drug Effects & Novel Drug Development

September 5-7, 2012 DoubleTree by Hilton Philadelphia Center City, USA

Rohidas Arote

Scientific Tracks Abstracts: J Neurol Neurophysiol

Abstract :

Primary objectives of gene therapy are to correct the genetic defects that underlie a disease process and to providesupplemental therapeutic modality through genetic engineering. Over 75% of current gene therapy is performed using virusesas gene delivery vehicles. However, with viruses, there are serious concerns over the issues of toxicity, immunogenicity,payload gene size limitations, and difficulty in scale up for industrial production. Non-viral vectors therefore have attractedattention from academic and industrial point of view. Among the non-viral vectors, polymeric systems offer several important advantages. First, polymers are tremendously versatile and can provide physical, chemical, and biological properties that are necessary for gene delivery applications. Second, polymers can be synthesized in parallel synthesis pathways for high throughput screening of biocompatibility and transfection efficiency. Third, various formulations, designs, and geometric scanbe made from polymeric materials for specific types of gene delivery applications. Moreover, the surface chemistry ofpolymers can be easily modified with biological ligands for site specific targeting in the body. However, some nondegradablepolymers accumulate in the body resulting in the cytotoxicity and thus the reduction in their gene transfer ability.Even though, low molecular weight polymers, which can be eliminated via kidney is an alternative choice, exhibits lowercolloidal stability and DNA condensation due to their reduced number of electrostatic interactions thus reduced transfection efficiency. As biodegradable polymers are designed to contain a combination of various functional components, it is likely thatengineered systems for non-viral gene delivery, especially with the application of biodegradable ester linkage will eventuallybe constructed. This biodegradable linkage approach to vector development is giving way to a safety profile where lowmolecular weight polyethylenimines are couples with diacrylate linkers to yield high molecular weight poly(ester amine)s(PEAs) with reduced cytotoxicity and high transfection efficiency. For example, the initial emphasis on identifying materialsthat bind and condense nucleic acids may have underappreciated the importance of their subsequent cellular uptake; attentionhas now turned to vectors with a hydrophobic, biodegradable cross linker such as polycaprolactonediacrylate orhydrophilic, biodegradable cross linkers such as glycerol dimethacrylate and glycerol triacrylate whose chemicalstructure with ester linkage allowed the controlled fashioned degradation with suitable nucleic acid condensation, followingcellular uptake and thus gene delivery ability. The need for a safety and biocompatibility approach extends to in vitroinvestigations, as modifications intended for in vivo applicability can significantly affect both in vitro and in vivoperformance.

Biography :

Dr. Rohidas B. Arote has been studied with gene delivery for more than 7 years. He has been awarded as ?Young Scientist? inthe field of Gene Therapy. He published 45 international papers in the field of non-viral gene delivery. Recently he synthesized novelbiodegradable poly (ester amine) s based on glycerol dimethacrylate and low molecular weight polyethylenmine and thispolymer showed significant transfection efficiency in gene silencing activity in vitro as well in vivo for which he applied apatent in Korea. Currently he is an Assistant Professor at Seoul National University

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