(652d) Cellulose-Based Injectable Hydrogel Composite for pH-Responsive Drug Delivery

Zhaohui Tong^*,1, Nusheng Chen¹, Ling Chen ², and Wilfred Vermerris³

¹Department of Agricultural & Biological Engineering, University of Florida, PO Box 110570, Gainesville, FL 32611-0570, United States

² Department of Pediatrics, University of Florida, PO BOX 100215, Gainesville, FL, 32610-0215, United States

³Department of Microbiology and Cell Science & UF Genetics Institute, PO Box 103610, Gainesville, FL 32611

Abstract: Localized drug delivery, and prolonged, stimulus-driven release are approaches to maximize the function of drugs and minimize their side effects. This study developed a novel cellulose-based injectable hydrogel composite system containing pH responsive poly (ethylene oxide)-block-poly (2-(diisopropylamino) ethyl methacrylate) (PEO-b-PDPA) copolymer micelles for localized delivery and pH-triggered release. First, covalently in situ generated hydrogels were constructed by mixing hydrazide-modified carboxymethyl cellulose (CMC-NH₂) with oxidized carboxymethyl cellulose (CMC-CHO). The resultant hydrogels could be well tuned in the aspects of gelation time, degradation profile, and mechanical properties. Then, the pH-responsible copolymer PEO-b-PDPA was introduced to enhance the loading of hydrophobic substances in hydrogels as well as a pH-triggered release, which was demonstrated by fluorescent spectroscopy using Nile Red as a model drug. In addition, the results demonstrated that the hydrogel itself could act as a second diffusion barrier to reduce the drug release rate. The cell viability tests showed that both CMC-NH2 and hydrogels possessed excellent biocompatibility, while CMC-CHO was cytotoxic at a relative high concentration.