(631o) PEG-Grafted Chitosan As Biodegradable Gene Carriers to the Pulmonary Epithelium
Several pulmonary disorders may be targeted with gene therapy, including lung cancer, cystic fibrosis, asthma, and chronic obstructive pulmonary disease. However, there are many challenges that need to be overcome in order to successfully deliver genetic material to the respiratory tract. The mucus layer (upper airways), lung surfactant (alveoli), and alveolar macrophages are some of the most important extracellular barriers. Uptake, cellular trafficking, and release of the genetic material constitute the main intracellular barriers. In order to overcome such barriers, various gene carriers have been proposed. Polymeric gene carriers (polyplexes) have demonstrated advantages over viruses and lipids, but the polymer chemistry and the physical properties of the polyplexes are known to greatly affect the transfection process. In addition, the aerosolisation technique can also play a role in transfection efficiency, since the amount and location where the polyplexes are delivered depend on the device and on particle engineering. The formulation of such carriers is thus of great relevance as well.
In this work will discuss the transfection efficiency of polyethylene glycol grafted chitosan (CS-g-PEG) polyplexes in airway and alveolar cells in vitro. Those results will be compared with the efficiency of non-modified CS polyplexes. PEG has been selected, as it has been shown to reduce the clearance from alveolar macrophages, provide faster diffusion and less aggregation through the mucus layer, to interact less with pulmonary surfactant, to diminish serum protein coating, and also to enhance the stability of dispersed nanoparticles. The transfection results will be discussed based on transport studies of the polyplexes across a model mucosal layer, and their interaction with lung surfactant.
Key Words: Oral Inhalation, Gene Delivery, Lungs, In Vitro Transfection, Polyplexes, Mucus Layer, Lung Surfactant.
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