Elution characteristics of doxorubicin-loaded microspheres differ by drug-loading method and microsphere size.

PURPOSE: To examine the loading and elution behavior of doxorubicin and superabsorbent polymer microspheres (SAP-MS) as they relate to particle size and loading techniques. MATERIALS AND METHODS: SAP-MS, 30-60 µm and 50-100 µm, were subject to loading 50 mg of doxorubicin from a dry lyophilized state. Doxorubicin loading was performed after prehydration of SAP-MS (one-step method) or serially in two divided administrations (two-step method). Loading rate and elution characteristics were determined after doxorubicin analysis using a high-pressure liquid chromatography (HPLC) assay. All experiments were performed in triplicate. RESULTS: All systems showed the ability to load and elute doxorubicin effectively in the specified time frame (loading 15 minutes to 2 hours and elution 1 hour to 14 days). For the two loading methods, 30-60 µm SAP-MS showed no statistically significant difference in loading rate but a statistically significant difference in cumulative elution at 14 days (19.13 mg vs 17.83 mg, one-step vs two-step; P = .02). For the two loading methods, 50-100 µm SAP-MS showed no statistically significant difference in loading rate and no statistically significant difference in cumulative elution at 14 days (14.87 mg vs 12.77 mg, one-step vs two-step; P = .20). CONCLUSIONS: SAP-MS exhibit the ability to load and release doxorubicin. In comparing particle size and loading methods, higher cumulative elution rates were associated with smaller (30-60 µm) particle size and one-step loading. Higher elution from the one-step loading method may be due to release of unbound doxorubicin. Differences in the loading and elution of doxorubicin may depend on the increased surface area of smaller SAP-MS resulting in alterations of behavior of doxorubicin and its interactions with the polymer microspheres.

Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

Long-term outcome from uterine fibroid embolization with tris-acryl gelatin microspheres: results of a multicenter study.

PURPOSE: To determine the long-term outcome of uterine fibroid therapy (UFE) using tris-acryl gelatin microspheres (TAGM). MATERIALS: This was a multicenter prospective study of patients undergoing UFE with TAGM, and during this phase of the study, the clinical outcomes 3 years after treatment were assessed. Measures of outcome included the Ruta Menorrhagia Questionnaire, patient self-assessments of symptoms and impact on activities, patient satisfaction and health-related quality of life as measured by the SF-12. Long-term re-intervention rates were also assessed. The data were analyzed at each interval compared to baseline using appropriate statistical tests. RESULTS: Of the 102 patients enrolled, 96 patients had complete baseline data and of these, 69 (72%) had known outcomes at 3 years after treatment. Sixty-one patients (64%) completed long-term follow-up without major intervention. An additional 8 patients (8.3%) underwent fibroid surgery (7 hysterectomies and 1 myomectomy). Among those without intervention, at 3 years after treatment, the mean Ruta Questionnaire Score was 19.3, compared to 47.9 at baseline and 24.5 at 3 months (P <.01). At baseline, 57% of patients had extremely heavy bleeding, while only 2% had that complaint at 36 months. At 36 months, much or moderate improvement in pelvic pain occurred in 83% of patients, pelvic discomfort in 83%, and urinary problems in 69% and 84% were moderately or very satisfied with their outcome. CONCLUSIONS: Over the long-term, UFE using TAGM is effective and safe, with high levels of durable symptom control, improved health-related quality of life and patient satisfaction.