Amorphous solid dispersion (ASD) is an effective approach for oral delivery of drugs with poor aqueous solubility. Cellulose derivatives such as cellulose ω-carboxyesters are potential ASD polymers.1 Among many structural factors, the side chain length and the side chain functionality are believed critical in inhibiting crystallization. However, without chemistries that can afford cellulose derivatives in a mild, modular and efficient manner, systematic screening of ASD candidates and in-depth structure-property relationship study are difficult, if not impossible. Our recent study2 has focused on developing novel modification strategies towards cellulose esters with a broad range of functionalities and chain lengths but almost identical molecular weight, degree of substitution and substitution pattern. These approaches, including olefin cross-metathesis, thiol-Michael addition and hydroboration-oxidation, have generated polymeric derivatives with extraordinary crystallization inhibition performance. Moreover, informative structure-property relationship studies were conducted, providing guidance to future design and synthesis of the next generation of ASD polymers. References 1. Liu, H.; Ileybare, G. A.; Cherniawski, B. P.; Ritchie, E. T.; Taylor, L. S.; Edgar, K. J., Synthesis and structure-property evaluation of cellulose omega-carboxyesters for amorphous solid dispersions. Carbohydr. Polym. 2014, 100, 116-125. 2. (a) Meng, X.; Matson, J. B.; Edgar, K. J., Olefin cross-metathesis, a mild, modular approach to functionalized cellulose esters. Polym. Chem. 2014, 5 (24), 7021-7033; (b) Meng, X.; Matson, J. B.; Edgar, K. J., Olefin cross-metathesis as a source of polysaccharide derivatives: cellulose omega-carboxyalkanoates. Biomacromolecules 2014, 15 (1), 177-187; (c) Meng, X.; Edgar, K. J., Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis. Carbohydr. Polym. 2015, 132, 565-573; (d) Meng, X.; York, E. A.; Liu, S.; Edgar, K. J., Hydroboration–oxidation: A chemoselective route to cellulose ω-hydroxyalkanoate esters. Carbohydr. Polym. 2015, 133, 262-269.

Novel cellulose derivatives as amorphous solid dispersion matrices for oral drug delivery

251st National Meeting (2016)

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