Suitability of the nasal route for both local and systemic delivery of drug substances stems from several advantages including high vascularity, large surface area, avoidance of firstpass metabolism, ease of drug administration, rapid attainment of therapeutic blood drug levels and possibly high systemic bioavailability. In spite of these advantages, there are some challenges facing this non-invasive drug delivery approach. Rapid removal of administered drugs by respiratory mucociliary clearance system often results in low absorption, especially for large molecular weight compounds. This problem may be addressed using novel delivery systems such as mucoadhesive formulations. This chapter will focus on novel formulation strategies with synthetic biopolymers for systemic drug delivery via the nasal route.