12th International Conference of Pharmaceutical Sciences

Combination therapy that uses multiple drugs against different molecular targets should be considered interesting alternatives for treating complex diseases such as glioblastoma (GBM). Drugs like alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) are already explored for their capacity to act against different hallmarks of cancer1; . Previous reports suggest that the simultaneous use of these drugs, as a novel combining approach, might result in additive or synergistic effects2. Therefore, advances in nanotechnology-based delivery systems will inevitably bring nano-mediated therapeutic gains to the proposed combination. Herein, nanotechnological tools were employed by the development of polymeric nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) and chitosan for CHC encapsulation. Furthermore, these structures were conjugated with CTX by supramolecular forces. Thus, the present study was undertaken to investigate the effectiveness of developed conjugated nanoparticles (NPs).
PLGA-Chitosan NPs were prepared using a previously described nanoprecipitation method3. In summary, PLGA polymer and CHC were dissolved in 2 mL acetone. The solution was added into 5mL aqueous solution containing Pluronic® 188 50mg and trimethyl-chitosan 5mg. NPs were collected using centrifugation. Further, CHC-loaded NPs were combined with CTX through supramolecular association. For in vitro analysis of therapeutic efficacy glioma cell lines U251 were plated into 96-well plates at a density of 2x103. Thereafter, different treatments were applied and cell viability was assessed by sulphorhodamine B.
As a result, the current study provides indications that encapsulation of the CHC drug into the nanoparticles increased its individual therapeutic capacity. In addition, conjugation with CTX seemed to enhance therapeutic efficacy. Thus, developed nanostructured delivery systems exhibited a set of favorable attributes and a potential to be applied as a promising new alternative for GBM treatment.