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Preparation and in vitro evaluation of polylactic acid-mitomycin C microcapsules
D C Tsai1, S A Howard, T F Hogan
1School of Pharmacy, West Virginia University Medical Center, Morgantown 26506.
Abstract:
An emulsion method was developed for the incorporation of water-soluble mitomycin C into polylactic acid biodegradable microcapsules. With an average particle size of about 95 microns, microcapsules with a desired loading of from 3.65 to 13.80 per cent were prepared. These microcapsules, which contained both crystalline and finely dispersed drug particles, showed a dose-dependent drug release pattern with microcapsules of higher drug loading having a faster release rate than those of lower drug loading. Effective sterilization of the microcapsules for parenteral use was achieved by 60Co gamma-ray irradiation, which did not affect the microcapsule structure, release rate or drug stability. Mitomycin C showed dose-dependent antiproliferative activity against the growth of the K562 human erythroleukaemia cells. The microencapsulated dosage form of mitomycin C was found to enhance the drug's activity through sustained drug release. In experiments where drug concentrations in the cell medium were reduced according to the drug's biological half-life, the microcapsule systems showed a distinct advantage over the non-capsulated dose for the kinetic inhibition of K562 cell growth.
Insights
Biodegradable polylactic acid microcapsules effectively encapsulate mitomycin C, enhancing its antiproliferative activity against leukemia cells through sustained release. Sterilization methods preserved microcapsule integrity and drug efficacy for potential parenteral applications.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Mitomycin C is a potent chemotherapeutic agent with limitations in delivery and stability.
- Biodegradable polymers offer promising platforms for controlled drug release.
- Developing effective delivery systems for water-soluble drugs like mitomycin C is crucial for cancer treatment.
Purpose of the Study:
- To develop and characterize biodegradable polylactic acid (PLA) microcapsules for encapsulating water-soluble mitomycin C.
- To evaluate the drug release kinetics, sterilization efficacy, and antiproliferative activity of the microencapsulated mitomycin C.
- To compare the efficacy of microencapsulated mitomycin C with the free drug against K562 human erythroleukemia cells.
Main Methods:
- An emulsion method was employed to incorporate mitomycin C into PLA microcapsules.
- Microcapsule size, drug loading, and drug release patterns were analyzed.
- 60Co gamma-ray irradiation was used for sterilization, and its effects on microcapsule properties were assessed.
- Antiproliferative activity was evaluated against K562 cells in vitro.
Main Results:
- PLA microcapsules with an average size of 95 microns were successfully prepared, achieving drug loadings from 3.65% to 13.80%.
- Drug release was dose-dependent, with higher loading resulting in faster release rates.
- Gamma-ray irradiation effectively sterilized the microcapsules without compromising their structure, release profile, or drug stability.
- Microencapsulated mitomycin C demonstrated enhanced, dose-dependent antiproliferative activity against K562 cells, showing superior kinetic inhibition compared to the non-encapsulated form.
Conclusions:
- Biodegradable PLA microcapsules provide a viable system for delivering water-soluble mitomycin C.
- Sustained release from microcapsules enhances the antiproliferative efficacy of mitomycin C.
- Gamma-ray sterilization is a suitable method for preparing these microcapsules for parenteral administration.