原位凝胶是实现注射埋植给药的理想载体,凝胶水是药物存在的主要环境并对维持凝胶骨架形态有重要作用,而释药环境渗透压是影响凝胶水的重要因素.以壳聚糖/甘油磷酸钠温敏凝胶为例,研究了体内外渗透压变化引起的载药原位凝胶中水含量与组成变化,及其对释药的影响.由于生物组织与水中的渗透压差异,凝胶植入SD大鼠皮下后水分(主要是自由水)迅速流失,水含量最终接近周围组织,与其在体外溶胀、溶蚀的过程显著不同.通过在释放介质中加入PEG,对体外试验方法进行了改进,模拟研究了渗透压变化对释药的影响:凝胶自由水快速流失携带药物快速流出而出现突释；水分流失又使凝胶网络更致密、凝胶中剩余药物结晶析出,导致药物后期释放缓慢且不完全.控制凝胶水分变化是控制凝胶释药特征的重要方面.%The in situ gelling hydrogel shows considerable promise for injectable implant drug delivery. The water in the hydrogel, which plays the important role of storing drug and maintaining the hydrogel network, is considered to be significantly influenced by the osmotic pressure of the drug release environment. The present work, taking chitosan/glycerophosphate (CS/GP) thermosensitive hydrogel (a widely studied in situ gelling hydrogel) for instance, investigated the variation of hydrogel water content with the osmotic pressure and its impacts on drug release in vitro and in vivo. After the hydrogel was implanted into the SD rats, the water content of the CS/GP hydrogel, especially its free water content, quickly reduces and finally approaches the water content of the surrounding tissue. This case is far different from swelling and erosion process of the hydrogel in vitro because the osmotic pressures are different between the biological tissue and the in vitro release medium. The osmosis in vivo was simulated by adding PEG into the release medium and the impacts of water losing on drug release were explored. The results show that the quickly losing of free water containing drug causes the initial drug burst release, and causes the crystallization of the remained drug and the compaction of the hydrogel network which greatly hindered the subsequent drug release. The hydrogel water content variation should be governed for controlled drug release of the hydrogel.
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