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Purpose Camptothecin (CPT), a potent topoisomerase I inhibitor, was originally discovered as an anticancer agent to induce programmed cell death of cancer cells. Recent evidence suggests that, similar to cancer, alterations in apoptosis and over-proliferation of key effector cells in the arthritic joint result in rheumatoid arthritis (RA) pathogenesis. Initial in vitro studies have suggested that camptothecin inhibits synoviocyte proliferation, matrix metalloproteinases expression in chrondrocytes and angiogenesis. This study is one of the first to test, in vivo, RA as a new indication for CPT. Methods To circumvent insolubility, instability and toxicity of CPT, we used biocompatible, biodegradable and targeted sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). We also surface-modified CPT-SSM with vasoactive intestinal peptide (VIP) for active targeting. We then determined whether this nanomedicine abrogated collagen-induced arthritis (CIA) in mice. Results Based on our findings, this is the first study to report that CPT was found to be efficacious against CIA at concentrations significantly lower than usual anti-cancer dose. Furthermore, a single subcutaneous injection of CPT-SSM-VIP (0.1 mg/kg) administered to CIA mice mitigated joint inflammation for at least 32 days thereafter without systemic toxicity. CPT alone needed at least 10-fold higher dose to achieve the same effect, albeit with some vacuolization in liver histology. Conclusion We propose that CPT-SSM-VIP is a promising targeted nanomedicine and should be further developed as a safe, long-acting, disease-modifying pharmaceutical product for RA.

Chitosan has potential biomedical applications that may require the final products to be sterilized before use. The gamma irradiation of purified and highly deacetylated chitosan fibers and films at sterilizing doses (up to 25 kGy) caused main chain scissions. The viscosity average molecular weight of the polymer decreased with increasing irradiation dose, the radiation yields of scission being 1.16 in air and 1.53 in anoxia. Preirradiation application of a negative pressure of 100 kPa disrupted the network structure, which may have contributed to the greater radiation yield obtained by chitosan fibers in anoxia. Radiation induced scission of the chitosan chains resulted in a lower glass transition temperature (Tg), indicative of higher segmental mobility. The Tg was below ambient at an irradiation dose of 25 kGy in air. Irradiation in air improved the tensile strength of the chitosan film, probably due to changes in chain interaction and rearrangement. Irradiation in anoxia did not affect film properties significantly, partly because the preirradiation application of negative pressure had a negligible effect on the structure of the chitosan film. Polymer network structure and the irradiation conditions are therefore important determinants of the extent of radiation induced reactions in chitosan.

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