Elution Characteristics of Doxorubicin-loaded Microspheres Differ by Drug-loading Method and Microsphere Size

Abstract 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.