Prokopowicz Magdalena, Lukasiak Jerzy, Przyjazny Andrzej
Division of Physical Chemistry with Instrumental Analysis Laboratory, Medical Academy of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.
J Biomater Sci Polym Ed. 2004;15(3):343-56. doi: 10.1163/156856204322977229.
The sol-gel pre-doping method was used to encapsulate doxorubicin in silica gels and optimum conditions of preparation of drug-loaded gel were established, ensuring both reproducible and effective results of quantitative encapsulation of doxorubicin and its gradual but complete release. Doxorubicin was encapsulated in polysiloxane polymers using the method based on sol-gel encapsulation without a catalyst, with an acid catalyst (HCl) and a base catalyst (NH3). The time of gelation of the gel loaded with doxorubicin, encapsulation efficiency of the drug and the degree of release of the drug from the gel are all affected by the kind of catalyst (acidic or basic) or its absence at the gel preparation stage, and the temperature of the gelation process. The time of sol gelation when using the NH3 or HCl catalyst was 9 days at 21 degrees C, 2 days at 30 degrees C and 1.5 days at 37 degrees C, while for the gel prepared without a catalyst it was 90 days at 21 degrees C, 75 days at 30 degrees C and 70 days at 37 degrees C. The efficiency of doxorubicin encapsulation was 99.5 +/- 0.5% (w/w) for acid-catalyzed gel, 98.9 +/- 1.01% (w/w) for base-catalyzed gel and 86.4 +/- 11.6% (w/w) for non-catalyzed gel. A 100% (w/w) release of doxorubicin by diffusion through pores was found only in the case of base-catalyzed gel after a 140-h incubation time. For acid-catalyzed gel and non-catalyzed gel, the total amounts of released doxorubicin after 140 h of incubation were 3-5% (w/w) and 9-11% (w/w), respectively. The stability of doxorubicin encapsulated in the three kinds of gel matrices was found to be improved compared to the stability of a free form of the drug in solution.
采用溶胶 - 凝胶预掺杂法将阿霉素包封于硅胶中，并确定了载药凝胶的最佳制备条件，确保阿霉素定量包封结果具有可重复性且有效，同时实现其逐步但完全的释放。基于无催化剂、酸催化剂（HCl）和碱催化剂（NH₃）的溶胶 - 凝胶包封法，将阿霉素包封于聚硅氧烷聚合物中。载有阿霉素的凝胶的凝胶化时间、药物包封效率以及药物从凝胶中的释放程度均受凝胶制备阶段催化剂类型（酸性或碱性）或无催化剂情况以及凝胶化过程温度的影响。使用NH₃或HCl催化剂时，溶胶凝胶化时间在21℃下为9天，30℃下为2天，37℃下为1.5天；而无催化剂制备的凝胶在21℃下为90天，30℃下为75天，37℃下为70天。酸催化凝胶的阿霉素包封效率为99.5±0.5%（w/w），碱催化凝胶为98.9±1.01%（w/w），非催化凝胶为86.4±11.6%（w/w）。仅在碱催化凝胶孵育140小时后，发现通过孔扩散实现了阿霉素100%（w/w）的释放。对于酸催化凝胶和非催化凝胶，孵育140小时后阿霉素的释放总量分别为3 - 5%（w/w）和9 - 11%（w/w）。与溶液中游离形式的药物稳定性相比，发现阿霉素包封于三种凝胶基质中的稳定性有所提高。
