This study is focused on the crucial issue of biodegradability of graphene under in vivo conditions. Characteristic Raman signatures of graphene are used to three dimensionally (3D) image its localization in lung, liver, kidney and spleen of mouse and identified gradual development of structural disorder, happening over a period of 3 months, as indicated by the formation of defect-related D'band, line broadening of D and G bands, increase in ID /IG ratio and overall intensity reduction. Prior to injection, the carboxyl functionalized graphene of lateral size ∼200 nm is well dispersed in aqueous medium, but 24 hours post injection, larger aggregates of size up to 10 μm are detected in various organs. Using Raman cluster imaging method, temporal development of disorder is detected from day 8 onwards, which begins from the edges and grows inwards over a period of 3 months. The biodegradation is found prominent in graphene phagocytosed by tissue-bound macrophages and the gene expression studies of pro-inflammatory cytokines indicated the possibility of phagocytic immune response. In addition, in vitro studies conducted on macrophage cell lines also show development of structural disorder in the engulfed graphene, reiterating the role of macrophages in biodegradation. This is the first report providing clear evidence of in vivo biodegradation of graphene and these results may radically change the perspective on potential biomedical applications of graphene.

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Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.

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