Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4h after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.

Cyanoacrylate(CA)-based tissue adhesives, although not widely used, are a feasible option to fix a mesh during abdominal hernia repair, due to its fast action and great bond strength. Their main disadvantage, toxicity, can be mitigated by increasing the length of their alkyl chain. The objective was to assess the in vitro cytotoxicity and in vivo biocompatibility in hernia repair of CAs currently used in clinical practice (Glubran(n-butyl) and Ifabond(n-hexyl)) and a longer-chain CA (OCA(n-octyl)), that has never been used in the medical field. Formaldehyde release and cytotoxicity of unpolymerized(UCAs) and polymerized CAs(PCAs) were evaluated by macroscopic visual assessment, flow cytometry and Alamar Blue assays. In the preclinical evaluation, partial defects were created in the rabbit abdominal wall and repaired by fixing polypropylene prostheses using the CAs. At 14 days post-surgery, animals were euthanized for morphology, macrophage response and cell damage analyses. Formaldehyde release was lower as the molecular weight of the monomer increased. The longest side-chain CA(OCA) showed the highest cytotoxicity in the UCA condition. However, after polymerization, was the one that showed better behavior on most occasions. In vivo, all CAs promoted optimal mesh fixation without displacements or detachments. Seroma was evident with the use of Glubran, (four of six animals: 4/6) and Ifabond (2/6), but it was reduced with the use of OCA (1/6). Significantly greater macrophage responses were observed in groups where Glubran and Ifabond were used vs. sutures and OCA. TUNEL-positive cells were significantly higher in the Glubran and OCA groups vs. the suture group. Although mild formaldehyde release occurred, OCA was the most cytotoxic during polymerization but the least once cured. The CAs promoted proper mesh fixation and have potential to replace traditional suturing techniques in hernia repair; the CAs exhibited good tissue integration and effective short-term biocompatibility, with the slightest seroma and macrophage response induced by OCA.