These results demonstrate that TNF-alpha upregulated malignant melanoma migration in vitro and that this could be reduced by ibuprofen both in solution and delivered from a hydrogel. These effects of ibuprofen cannot be attributed simply to induction of apoptosis.

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Abnormal regulation of apoptosis is an important aspect of tumour development. Capsaicin, an extract of red chilli peppers, has been shown to inhibit growth of melanoma and other malignant cell lines and HA14-1 is an organic compound that directly induces apoptosis by binding to Bcl-2 protein. The aim of this work was to investigate whether combination therapy with capsaicin and HA14-1 might hold any promise for the treatment of melanoma. Three melanoma cell lines of a range of aggressive potential, melanocytes and fibroblasts were examined, looking at the effects of both drugs singly and in combination on cell viability and induction of apoptosis. This comparative study showed that melanoma cells and melanocytes have a similar sensitivity to capsaicin while fibroblasts are more resistant to it. HA14-1, as expected, induced apoptosis in all cells at relatively low concentrations. A combination of the two agents produced the expected results of an additive effect for 2 (HBL and A375SM) out of 3 melanoma cell lines in inducing apoptosis, but encouragingly for the most metastatically aggressive cancer cell line (C8161), a combination of the two showed a synergistic induction of apoptosis.

Superoxide dismutase (SOD) and catalase (CAT) are active scavengers of reactive oxygen species and were incorporated into ultradeformable vesicles with the aim of increasing enzyme bioavailability (skin delivery). These special very adaptable vesicles have been formulated and optimized for enzyme transport in order to penetrate into or across the intact skin barrier. Anti-inflammatory activity of SOD-loaded, CAT-loaded and of SOD- and CAT-loaded ultradeformable vesicles applied epicutaneously was measured using different protein doses on the skin, on an arachidonic acid-induced mouse ear oedema. The biological anti-oedema activity is a measurement of drug-targeting potentiation in the organ. Delivery by means of deformable vesicles was compared to conventional vesicles or the absence of an enzyme carrier mediated transport. This was done at various times following prophylactic application of the test formulations. Positive reference groups were treated epicutaneously with several low molecular weight non-steroidal anti-inflammatory drugs (NSAIDs). The latter included indomethacin (3 mg kg(-1)), etofenamate (30 mg kg(-1)) and piroxicam (1 mg kg(-1)) and reduced the oedema by 94 +/- 4%, 81 +/- 4% and 42 +/- 5%, respectively, if measured 30 min after ear treatment with a NSAID. Of the enzyme-loaded carriers tested, only the enzyme-loaded ultradeformable vesicles reduced the swelling of ears significantly: SOD (90 microg kg(-1)), CAT (250 microg kg(-1)) and SOD (90 microg kg(-1)) plus CAT (250 microg kg(-1)) reduced the oedema by 70 +/- 12%, 65 +/- 10% and 61 +/- 19%, respectively, at t = 30 min. Aqueous enzyme solutions and empty carriers had no such effect. The combination of two enzymes resulted in no increased therapeutic effect, but the results are inconclusive since only two dose combinations were tested. The results presented in this study suggest that antioxidant enzymes delivered by means of ultradeformable lipid vesicles can serve as a novel region-specific treatment of inflammation.