Tailoring the Network Properties of Ca~(2+) Crosslinked Aloe vera Polysaccharide Hydrogels for in Situ Release of Therapeutic Agents

摘要

Properties of Aloe vera galacturonate hydrogels formed via Ca~(2+) crosslinking have been studied in regard to key parameters influencing gel formation including molecular weight, ionic strength, and molar ratio of Ca~(2+) to COO~ functionality. Dynamic oscillatory rheology and pulsed field gradient NMR (PFG-NMR) studies have been conducted on hydrogels formed at specified Ca~(2+) concentrations in the presence and absence of Na~+ and K~+ ions in order to assess the feasibility of in situ gelation for controlled delivery of therapeutics. Aqueous Ca~(2+) concentrations similar to those present in nasal and subcutaneous fluids induce the formation of elastic Aloe vera polysaccharide (AvP) hydrogel networks. By altering the ratio of Ca~(2+) to COO~- functionality, networks may be tailored to provide elastic modulus (G') values between 20 and 20000 Pa. The Aloe vera polysaccharide exhibits time-dependent phase separation in the presence of monovalent electrolytes. Thus the relative rates of calcium induced gelation and phase separation become major considerations when designing a system for in situ delivery applications where both monovalent (Na~+, K~+) and divalent (Ca~(2+)) ions are present. PFG-NMR and fluorescence microscopy confirm that distinctly different morphologies are present in gels formed in the presence and absence of 0.15 M NaCl. Curve fitting of theoretical models to experimental release profiles of fluorescein labeled dextrans indicate diffusion rates are related to hydrogel morphology. These studies suggest that for efficient in situ release of therapeutic agents, polymer concentrations should be maintained above the critical entanglement concentration (C_e, 0.60 wt %) when [Ca~(2+)]/[COO~-] ratios are less than 1. Additionally, the monovalent electrolyte concentration in AvP solutions should not exceed 0.10 M prior to Ca~(2+) crosslinking.