Study On Preparation Of Injectable Hydrogels And Drug-Releasing Performance

Intelligent hydrogel is one of the important functional polymer materials which has response to the external environment. The injectable hydrogel for its unique phase transition behavior is expected to be widely used in the field of drug release. However, there are two problems about it. One is that polymer solution doesn't inject into the body because it gelatinates rapidly in the needle tube with change of temperature. Another is injectable hydrogel can not degrade rapidly, so resulting in tissue inflammation.In this dissertation, the synthesis of biodegradable star-shaped PLLA-PEG multi-block copolymer, the preparation of injectable hydrogel and the release behavior in vitro were researched successfully. The main conclusions of this dissertation are summarized as follow:(1) Pentaerythritol as the initiator, PET-PLLA was synthesized by ring-opening polymerization of L-lactide. The chemical stucture was characterized by NMR, and the reaction conditions were studied. The results showed that concentration of pentaerythritol and polymerization time play a key role on molecular weight of PET-PLLA. When the mole ratio of PET-PLLA and succinic anhydride was 1:8, the mole ratio of PET-PLLA and DMAP was 1:2, reaction time was 48h and reaction temperature was 30℃, the PET-PLLA-SA has the largest yield and the most number of carboxyl group. And the synthetic technological conditions of PET-PLLA-SA-PEG were optimized. We found that the yield of product was influenced significantly by the concentration of PEG, solvent quantity, concentration of DMAP and DCC, and the swelling degree(SD) of polymer was influenced significantly by the concentration of PEG, solvent quantity, reaction time, and concentration of DCC.(2) Polymer's SD can be controlled by changing block ratio of star-shaped PLLA-PEG multi-block copolymer. The results showed that the polymer's SD decrease with the increase of PLLA hydrophobic block ratio and increase with the increase of PEG hydrophilic block ratio. Furthermore, polymer swelling was fastest and SD was the biggest when in 37℃water. 30wt% polymer solution to gel has the upper critical temperature is human body temperature.(3) In vitro release of Urapidil Hydrochloride from injectable hydrogel was performed by oscillating in constant temperature. The release study indicated that the Urapidil Hydrochloride embedded in star-shaped PLLA-PEG copolymer hydrogel exhibited better sustained-release capacity. There are two drug release behavior in whole release process. One could be described by first order release equation and the other could be described by Higuchi release equation. Ritger-Peppas dynamic model further interpreted the second stage release behavior.