Page - (000363) - in Biomedical Chemistry: Current Trends and Developments

nanocarrier (Hu, 2010; Kratz, 2012; Zhang, 2011), and even more challenging to deliver such cargos in vivo, where it is absolutely necessary to supply the proper drug ratio at the tumor level (Mayer, 2006). Several nanoparticulate systems such as lipid-based, inorganic and polymeric nanoparticles, among other types, have been used to co- load two or more different payloads adopting different strategies (Hu, 2010). Some include the physical adsorption of drugs to the nanovector, with the disadvantage that only drugs with similar physicochemical properties can be loaded simultaneously (Herranz-Blanco, 2014; Liu, 2012; 2014a). It is also possible to co-load molecules with different physicochemical properties via a sequential adsorption procedure (Liu, 2013a). Others have followed the incorporation of therapeutics into the particle matrix during particle preparation (Doane, 2013), and covalently bonded the drug molecules to the polymeric backbone after particle preparation (Aryal, 2011). Despite the obstacles encountered in cancer therapy, extensive progress has been made so far and nowadays there are several nanoformulations that combine two or more different anticancer drugs (Liao, 2014; Tardi, 2009) or even two different classes of therapeutics (Deng, 2013; Liu, 2014b; Saad, 2008). For example, a nanoparticulate system was developed by Deng using a layer-by-layer deposition approach (Deng, 2013). Liposomes were chosen to be encapsulated by polycationic PLA through the layer-by-layer deposition, and finally coated by a layer of hyaluronic acid that enhances the in vivo stability of the nanosystem (Poon, 2011). This system co-delivered siRNA molecules and doxorubicin loaded in the core of the liposomes, which were able to knockdown a drug resistance pathway in tumor cells (Whitehead, 2009). This means they can be applied in the treatment of triple-negative breast cancer form, which is an estrogen, progesterone and human epidermal growth factor receptor 2 (HER2)-negative cancer type with a more aggressive effect than other breast cancers (Kassam, 2009; Livasy, 2006). The successful co-delivery of both siRNA and doxorubicin was achieved, as well as significantly enhanced DXR efficacy by 4-fold in vitro (Fig. 3.5.6). The in vivo results showed an 8-fold decrease in tumor volume compared to the control treatments, with no observed toxicity to the animals. An ultimate outer layer of hyaluronic acid (HA) was