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[Daunomycin-human albumin microspheres (dau-ha-ms)--preparation, characterization and use in experimental cancer
R Z Wang1, W Q Zhong, S R Guan
1Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing.
Abstract:
For the purpose of enhancing the therapeutic index and reducing the toxic effect of chemotherapeutic drugs, Dau-HA-Ms was prepared, mostly as monodispersed microspheres with a mean diameter of 52 +/- 16 microns, ranging from 29 to 194 microns, being suitable for the use of transarterial embolization (TAE) therapy. Dau released effectively in physiological saline solution from microspheres without burst release. The spectrophotometric characteristics and cytotoxic effect in vitro of the released Dau remained unchanged, retaining the original physicochemical and biological properties. It was demonstrated that 30% of mice bearing S-180 sarcoma ascites treated with intraperitoneal injection of Dau-HA-MS survived longer than 6 months, while all tumor bearing control mice and Dau treated tumor bearing mice died within 21 and 14 days, respectively. The results show that Dau-HA-MS is therapeutically more effective and less toxic than Dau, Dau-HA-MS can possibly be used in TAE therapy for human liver cancer.
Insights
Dau-HA-microspheres (Dau-HA-Ms) show improved therapeutic effectiveness and reduced toxicity compared to free Dau. This novel formulation holds promise for transarterial embolization (TAE) therapy in liver cancer treatment.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Oncology
Context:
- Chemotherapeutic drugs often have a narrow therapeutic index, limiting their clinical efficacy due to systemic toxicity.
- Transarterial embolization (TAE) is a localized cancer treatment method that can benefit from controlled drug release formulations.
- Developing novel drug delivery systems is crucial for enhancing cancer treatment outcomes.
Purpose:
- To prepare and characterize Dau-HA-microspheres (Dau-HA-Ms) for improved chemotherapeutic delivery.
- To evaluate the drug release profile, physicochemical properties, and in vitro cytotoxicity of Dau-HA-Ms.
- To assess the in vivo therapeutic efficacy and toxicity of Dau-HA-Ms in a murine cancer model.
Summary:
- Dau-HA-microspheres were successfully prepared with a mean diameter of 52 ± 16 microns, suitable for TAE.
- Dau was released effectively from the microspheres without burst release, retaining its original properties.
- In vivo studies showed that Dau-HA-Ms significantly prolonged survival in tumor-bearing mice compared to free Dau and controls.
Impact:
- Dau-HA-Ms demonstrate enhanced therapeutic efficacy and reduced toxicity, suggesting potential for improved cancer treatment.
- The microsphere formulation is suitable for transarterial embolization (TAE) therapy.
- This study supports the potential clinical application of Dau-HA-Ms for human liver cancer treatment.