This chitosan films containing added glycerol and either granulocyte-macrophage colony-stimulating factor (GM-CSF) or PEGlyated GM-CSF, PEG-(GM-CSF) were prepared and characterized for their release rates. Chitosan is a natural, mucoadhesive, and cationic polymer that is soluble in dilute acetic acid solutions(1). Thus, formulations can be prepared to deliver negatively charged compounds without the use of denaturing solvents. These formulations should exhibit increased residence time in contact with the mucosa. Further, chitosan may expand cell-cell junctions allowing for uptake of PEG-(GM-CSF). GM-CSF is a 14.5 kD negatively charged (pl approx 5) glycoprotein that can form complexes with positively charged chitosan. GM-CSF has been shown to stimulate the growth and maturation of hematopoietic cells. PEGylation of proteins increases their plasma half-lives while decreasing their immunogenic properties. PEG can also hydrogen bond with chitsoan, slowing the elease of the PEGylated protein. Previous work has shown that PEG-(G-CSF) can be delivered across the mucosa via the enteral and pulmonary routes (2-3). Finally, glycerol is an FDA-approved additive that can hydrogen bond to both PEG and chitosan chains.
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