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Colloids Surf B Biointerfaces ; 170: 596-608, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-29975908

ABSTRACT

The use of hybrid materials, where a matrix sustains nanoparticles controlling the release of the chemotherapeutic drug, could be beneficial for the treatment of primary tumors prior or after surgery. This localized chemotherapy would guarantee high drug concentrations at the tumor site while precluding systemic drug exposure minimizing undesirable side effects. We combined bacterial cellulose hydrogel (BC) and nanostructured lipid carriers (NLCs) including doxorubicin (Dox) as a drug model. NLCs loaded with cationic Dox (NLCs-H) or neutral Dox (NLCs-N) were fully characterized and their cell internalization and cytotoxic efficacy were evaluated in vitro against MDA-MB-231 cells. Thereafter, a fixed combination of NLCs-H and NLCs-N loaded into BC (BC-NLCs-NH) was assayed in vivo into an orthotopic breast cancer mouse model. NLCs-H showed low encapsulation efficiency (48%) and fast release of the drug while NLCs-N showed higher encapsulation (97%) and sustained drug release. Both NLCs internalized via endocytic pathway, while allowing a sustained release of the Dox, which in turn rendered IC50 values below of those of free Dox. Taking advantage of the differential drug release, a mixture of NLCs-N and NLCs-H was encapsulated into BC matrix (BC-NLCs-NH) and assayed in vivo, showing a significant reduction of tumor growth, metastasis incidence and local drug toxicities.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Breast Neoplasms/drug therapy , Cellulose/chemistry , Doxorubicin/pharmacology , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Lipids/chemistry , Nanoparticles/chemistry , Acetobacteraceae/chemistry , Animals , Antibiotics, Antineoplastic/administration & dosage , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Cell Survival/drug effects , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems , Drug Screening Assays, Antitumor , Female , Humans , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Nude , Particle Size , Surface Properties , Tumor Cells, Cultured
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