Microspheres as a drug delivery system in cancer therapy

Abstract

Microspheres are an example of a drug delivery system that has been evaluated extensively in cancer chemotherapy. They are essentially solid porous particles (1 - 100 μm diameters) which can both target their drug cargo by physical trapping in blood vessels (chemoembolisation) and sustain the action of a therapeutic agent through controlled release. Microspheres can be made from a broad range of polymeric materials, including proteins, polysaccharides, polyesters and lipids by a variety of different techniques (emulsification, heat stabilisation, coacervation and phase inversion technology). Their diversity identifies the microsphere as a drug delivery system with considerable flexibility. The present review develops the hypothesis that the matrix material and method of preparation are critical determinants in defining pharmaceutical characteristics, which in turn dictate biologic activity. Examples are cited of different approaches adopted with cytotoxic drugs (chiefly doxorubicin, mitomycin C, cisplatin and 5-fluorouracil) to achieve particular drug delivery profiles. However, it is clear that certain cytotoxic drugs are encapsulated in systems with pharmaceutical properties inappropriate for the particular mechanistic class. Also, studies demonstrating selective tumour targeting of cytotoxic drugs after systemic administration are rare. This review also focuses on the contribution that microspheres have made to delivery of immunomodulating cytokines, protein vaccines, antisense oligonucleotides and gene therapy. For these applications, new matrix materials such as bioadhesive polymers and more gentle methods of preparation have had to be developed to preserve the native conformation of these easily denatured biological molecules. Nevertheless, these systems require to be subjected to pharmaceutical characterisation and need further optimisation to overcome persistent instability problems. Microspheres are anticipated to contribute significantly in the future to the systemic, oral and loco-regional treatment of cancer with cytotoxic drugs and biological response modifiers.