ethyl-cellulose and Neoplasms

While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.

Topics: Animals; Catheter Ablation; Cell Line, Tumor; Cell Survival; Cellulose; Cricetinae; Disease Models, Animal; Ethanol; Female; Humans; Injections, Intralesional; Neoplasms; Phantoms, Imaging; Treatment Outcome; Tumor Burden; Xenograft Model Antitumor Assays

Even though 5-fluorouracil has been demonstrated to display antitumor activity against a wide variety of cancers, high doses are needed to bring out the required therapeutic activity that could simultaneously lead to severe side effects. We hypothesized that the efficient delivery of 5-fluorouracil to tumors using a magnetic nanoplatform could reduce the dose required to obtain sufficient anticancer response. Thus, we have formulated a 5-fluorouracil-loaded magnetic nanomedicine consisting of a magnetic core (iron) and a biocompatible polymeric shell (ethylcellulose). These core/shell nanoparticles were synthesized by an emulsion solvent evaporation process, and 5-fluorouracil loading was assayed by surface incorporation onto the preformed nanocomposites, and by drug incorporation into the magnetic colloid. The contributions of both the surface and the polymeric network to the overall drug loading were investigated by means of optical absorbance and electrophoretic mobility determinations. 5-Fluorouracil entrapment into the polymeric matrix yielded a higher drug loading and a slower drug release profile as compared with drug adsorption. These preliminary results suggest the potential of this stimuli-sensitive drug carrier for cancer targeting.

Topics: Antimetabolites, Antineoplastic; Biocompatible Materials; Cellulose; Drug Delivery Systems; Fluorouracil; Iron; Nanostructures; Neoplasms