Preparation And Properties Of Modified Hyaluronic Acid Drug Carrier

In the thesis, hyaluronan (HA) was chemically modified with adipic dihydrazide (ADH), forming the HA-ADH film. The structure and capability of HA-ADH were characterized. In order to estimate the potential of the HA-ADH in drug delivery, hydrophobic and hydrophilic drug were used as the model drugs to prepare drug/HA-ADH films and microspheres. In phosphate buffer solution (Na₂HPO₄-KH₂PO₄, pH 7.3), the drug releasing properties of films and microspheres were measured by UV-Vis absorption spectrophotometric methods.(1) HA-ADH films were prepared with a solvent evaporation method. After cross-linking, DSC analysis indicated that microstructure of the product was obviously altered. The dried film had strong ability of water uptake, and an obvious network structure was detected by SEM, after the film swelled in buffer. Intrinsicviscosity [η] was measured with capillary viscometry, and [η] of HA and HA-ADHare 15.18(100mL/g) and 20.21(100mL/g), respectively. Viscosity, carbazole and lose weight methods indicate that HA-ADH is a degradable material, and degradation velocity of HA-ADH has a notable decrease, compared with HA. After modification, there was a notable decrease in water uptake and soluble ability of HA-ADH, which could prolong the reservation time of the polymer in phosphate buffer solution.(2) Based on the above results, GS/HA-ADH microspheres were made in a W/O emulsion, when GS was used as a model drug. SEM images show that the surface of the microsphere was not smooth, and the inside was loosen. The releasing behavior in buffer of the GS/HA-ADH microspheres was studied by UV-Vis.(3) In addition, the drug releasing property of HA-ADH drug loading film was investigated in vitro, when the hydrophobic TDZ and hydrophilic CEZ were used as the model drugs. UV-Vis absorption spectroscopic measurements demonstrated that CEZ/HA-ADH had a rapid-release behavior, in initial 30 minutes, cumulative release percent of CEZ was 47.0%. Oppositely, TDZ/HA-ADH had a slow-release behavior, in initial 30 minutes, cumulative release percent of TDZ was 9.8%. Then a sustained release property was found, going with a first order kinetics behavior. lasty, total cumulative release percent of drug was 87.5%, and the remainder drug could release with the degradation of the film. Drug release tests indicate that the HA-ADH film is an excellent sustained release dosage of hydrophobic TDZ. It is due to the combination of the hydrophobicity of TDZ and the slow swelling and degradation of HA-ADH film, and drug release was controlled by diffusion-controlled mechanism.