Study On Self-aggregate And Drug Release Profiles Of Cholic Acid Hydrazide-Dextran Conjugates

Cholic acid hydrazide-dextran conjugates (CAH-DEX) with stable acryl hydrazonelinkage were prepared from cholic acid hydrazide and polyaldehyde dextran in mildconditions, and the physicochemical properties of the CAH-DEX self-aggregates wereinvestigated by fluorescent spectroscopy, dynamic light scattering method, surfacetension and turbidity measurements. We prepared the indomethacin(IMC) anddoxthorubicin(DOX) loaded CAH-DEX self-aggregates, study the drug release profilein-vitro, and also do research on the surface modification of CAH-DEX self-aggregates. FTIR and H NMR were utilized to characterize the structure of CAH-DEX: FTIR 1spectrum of CAH-DEX contained a new peak appearing at 1662cm-1 due to acrylhydrazone, and had C-H strech absorption bands at 2866 and 2935cm-1 due to cholic acid;In the H NMR spectrum of CAH-DEX, the signal of proton of steroidal methyl group in 1cholic acid appeared at 0.59, 0.81, 0.94ppm. The amphiphilic CAH-DEX conjugates can self-aggregate into nanoscale structure,and experimental results shows: 1.CAH-DEX developed lower critical aggregateconcentration (CAC), which were determined by fluorescent spectroscopy to be 0.96,0.88and 0.46×10-2g/L for CAH-DEX(1/3)6.5%, CAH-DEX(1/3)9.0%, CAH-DEX(1/3)13.4%, respectively; 2.CAH-DEX can decrease the surface tension of the aqueoussolution, and the surface tension of conjugate solutions can rapidly be decreased with theincrease of CAH-DEX concentration. The turbidity increased when the concentration ofCAH-DEX enhanced, and the turbidity can maintain stable in the range of pH4-8.5; 3.The CAH-DEX self-aggregates were observed as spherical shapes and their dried sizeswere ranged between 50-70nm by transmission electron microscopy (TEM) and atomicforce microscopy (AFM). The hydrated self-aggregates sizes were ranged 200-300nm. CAH-DEX self-aggregates can effectively entrap water-insoluble drugs. IMC-loadedCAH-DEX self-aggregates were prepared by dialysis method, and the highest drugcontent was 29.9wt%, suggesting a loading efficiency of 51.2%. IMC was released fromCAH-DEX self-aggregates in pH 4 much slower than pH 7.4, and in pH 4 the releaseprofile was pseudo Zero-order in kinetic terms for up to 14 days, in contrast, in pH 7.4drug release last for 48h. DOX can be entrapped into CAH-DEX self-aggregates, and thedrug content can be 11.2%. Acceleration of DOX release can be obtained by lowering thesurrounding pH from 7.4 to 4. Adipic acid dihydrazide can be attached to the surface ofCAH-DEX self-aggregates to realize the surface modification with amino group, whichwas the basis to attach targeting moieties and other bioactive components.