Burton M A, Chen Y, Atkinson H, Codde J P, Jones S K, Gray B N
University of Western Australia, Department of Surgery, Royal Perth Hospital.
Int J Hyperthermia. 1992 Jul-Aug;8(4):485-94. doi: 10.3109/02656739209037986.
The utility of microspheres as targeted drug delivery agents is addressed with reference to using heat during formulation and to administration in combination with hyperthermia. It was demonstrated that rate of loading of the drug doxorubicin onto resin microspheres is enhanced under conditions of elevated temperature but this was shown to increase the incidence of microsphere aggregation. Total amount of drug loaded was related to time rather than temperature such that low temperature loading for up to 24 h produced optimum quality injectates. However, release of doxorubicin from microspheres was significantly increased during elevations of temperature to 43 degrees C. Thus, during hyperthermia doxorubicin release can be increased to provide periods of high drug availability targeted to tumour tissue for concomitant thermochemotherapy with microspheres. The therapeutic benefit derived from this combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the exteriorized liver at 43 degrees C for 30 min, while chemotherapy was administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into each tumour. Both hyperthermia and chemotherapy alone significantly reduced the size of tumours 10 days following treatment (p less than 0.01). However, in animals treated with both modalities, the size of tumours was significantly less than either treatment alone (p less than 0.05). These results provide a strong rationale for combining hyperthermia with targeted chemotherapy using microspheres.
本文探讨了微球作为靶向给药载体的效用，涉及制剂过程中加热的使用以及与热疗联合给药的情况。结果表明，在高温条件下，阿霉素加载到树脂微球上的速率会提高，但这也会增加微球聚集的发生率。药物的总加载量与时间而非温度相关，即低温加载长达24小时可产生质量最佳的注射剂。然而，当温度升高到43摄氏度时，阿霉素从微球中的释放量会显著增加。因此，在热疗过程中，阿霉素的释放量可增加，从而为肿瘤组织提供高药物可利用期，以便与微球进行同步热化疗。对20只植入VX2肝癌的兔子评估了这种联合治疗的疗效。通过2450兆赫微波施加器将肝脏外置部分加热到43摄氏度，持续30分钟进行热疗，同时通过向每个肿瘤内注射阿霉素微球（2.3毫克）进行化疗。单独的热疗和化疗在治疗10天后均显著减小了肿瘤大小（p<0.01）。然而，在接受两种治疗方式的动物中，肿瘤大小显著小于单独使用任何一种治疗方法（p<0.05）。这些结果为热疗与使用微球的靶向化疗相结合提供了有力的理论依据。
