The preparation of core-shell polymeric nanoparticles simultaneously loaded with
docetaxel (DTXL) and
doxorubicin (DOX) is reported herein. The self-assembly of the aliphatic biodegradable copolyester PBS/PBDL (
poly(butylene succinate-co-
butylene dilinoleate)) and
HPMA-based copolymers (N-(2-hydroxypropyl)methacrylamide-based copolymers) hydrophobically modified by the incorporation of
cholesterol led to the formation of narrow-size-distributed (PDI<0.10) sub-200-nm polymeric nanoparticles suitable for passive
tumor-targeting
drug delivery based on the size-dependent EPR (enhanced permeability and retention) effect. The PHPMA provided to the self-assembled nanoparticle stability against aggregation as evaluated in vitro. The highly hydrophobic
drug docetaxel (DTXL) was physically entrapped within the PBS/PBDL copolyester core and the hydrophilic
drug doxorubicin hydrochloride (DOX·HCl) was chemically conjugated to the reactive PHPMA copolymer shell via
hydrazone bonding that allowed its pH-sensitive release. This strategy enabled the
combination chemotherapy by the simultaneous DOX and DTXL
drug delivery. The structure of the nanoparticles was characterized in detail using static (SLS), dynamic (DLS) and electrophoretic (ELS) light scattering besides transmission electron microscopy (TEM). The use of nanoparticles simultaneously loaded with DTXL and DOX provided a more efficient suppression of
tumor-cell growth in mice bearing EL-4
T cell lymphoma when compared to the effect of nanoparticles loaded with either DTXL or DOX separately. Additionally, the obtained self-assembled nanoparticles enable further development of targeting strategies based on the use of multiple
ligands attached to an
HPMA copolymer on the particle surface for simultaneous passive and active targeting and different combination
therapies.