(442f) Use of Nanochannel Membranes to Regulate the Release of Cytokines From Biodegradable Reservoirs

The management of locally recurrent malignant melanoma continues to pose a significant challenge. These lesions are typically very painful, and currently available treatments such as repeated intratumoral injections of interferon-alpha (IFN-á) are costly and inconvenient. A particulate-like nanoporous miniature device (NMD) based on biodegradable polymer was developed for controlling local delivery of immunological agents to the tumor microenvironment. The main part of the device consists of a nanoporous controlled gate and a fabricated drug reservoir loaded with IFN-á. To improve the biocompatibility of the devices, a hydrophilic poly(ethylene glycol) monoacrylate was grafted onto the device. Microscopic visualization of the nanoporous controlled gate from in vitro experiments exhibited stability over the desired drug delivery period of two months. In vitro release experiments demonstrated linear release of IFN-á. The IFN-á released was biologically functional, as demonstrated by flow cytometric analysis of peripheral blood mononuclear cells for P-STAT1 (phosphorylated-signal transducer and activator of transcription 1) following exposure to the supernatants from the release experiments. We demonstrated that subcutaneous implantation of the NMDs was well tolerated and associated with an anti-tumor effect in a murine model of human melanoma. There was no evidence of significant inflammatory response or host encapsulation. Thus, these experiments show that our NMD can be fabricated and employed in vivo as a versatile drug delivery platform.