**4.2 Drug delivery system and formulation**

This approach aims to develop targeted delivery platforms for improving the permeation of doxorubicin/P-gp modulators/ chemo-sensitizers (e.g., antibodies against ABCB1, siRNA) into target cancer cells, leading to an increased intracellular doxorubicin concentration [3, 89, 96, 126–128]. Various nano-drug delivery platforms such as polymeric and solid lipid nanoparticle (SLNs), liposomes, micelles, mesoporous silica nanoparticles, nanostructured lipid carriers, dendrimers have been constructed to better targeting drug delivery to site of action. This approach

in couple with utilization of P-gp modulators can overcome MDR and enhance therapeutic efficacy of doxorubicin. Furthermore, with cancer-targeting ability, this target specific delivery would limit the adverse effect to normal tissues. With the encapsulation technology, nanoparticles (NPs) loaded with doxorubicin and P-gp modulators or other molecules (e.g., siRNAs) has been reported their effectiveness in target delivery into the cells. For examples, aerosol OT (AOT)-alginate NPs enhanced cellular delivery of doxorubicin in MCF-7 cells [129]. Lipid-modified dextran-based NPs loaded with doxorubicin and MDR1 siRNA significantly increased intracellular doxorubicin and reduced P-gp expression levels in osteosarcoma cell line, as compared to doxorubicin alone [130]. Doxorubicin-curcumin composite NPs (e.g., NanoDoxCurc, pegylated-DOX-CUR NPs) could enhance effects of doxorubicin both in vitro and in vivo models of DOX-resistant cancers (e.g., multiple myeloma, acute leukemia, prostate and ovarian cancers). In addition, doxorubicin-curcumin NPs did not cause cardiac toxicity and bone marrow suppression in mice model [131].
