title: Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization.
abstract: In past years, a considerable progress has been made in the conversion of conventional chemotherapy into potent and safe nanomedicines. The ultimate goal is to improve the therapeutic window of current chemotherapeutics by reducing systemic toxicities and to deliver higher concentrations of the chemotherapeutic agents to malignant cells. In this work, we report that PEGylation of the nanocarriers increases drug intracellular bioavailability leading therefore to higher therapeutic efficacy. The surface of the already patented solid lipid nanoparticles (SLN) loaded with paclitaxel (SLN-PTX) was coated with a PEG layer (SLN-PTX_PEG) through an innovative process to provide stable and highly effective nanoparticles complying with the predefined pharmaceutical quality target product profile. We observed that PEGylation not only stabilizes the SLN, but also modulates their cellular uptake kinetics. As a consequence, the intracellular concentration of chemotherapeutics delivered by SLN-PTX_PEG increases. This leads to the increase of efficacy and thus it is expected to significantly circumvent cancer cell resistance and increase patient survival and cure.
authors: Universidade de Lisboa, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Av. Professor Gama Pinto, 1649-004 Portugal.
authors: Alexandra
authors: A
authors: Arranja
authors: Universidade de Lisboa, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Av. Professor Gama Pinto, 1649-004 Portugal.
authors: Luís F
authors: LF
authors: Gouveia
authors: Drug Delivery and Targeting Group, Molecular Biology and Biochemistry Research Centre for Nanomedicine (CIBBIM-Nanomedicine), Vall d'Hebron Institut de Recerca, and Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
authors: Petra
authors: P
authors: Gener
authors: Universidade de Lisboa, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Av. Professor Gama Pinto, 1649-004 Portugal.
authors: Diana F
authors: DF
authors: Rafael
authors: Universidade de Lisboa, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Av. Professor Gama Pinto, 1649-004 Portugal.
authors: Carolina
authors: C
authors: Pereira
authors: Drug Delivery and Targeting Group, Molecular Biology and Biochemistry Research Centre for Nanomedicine (CIBBIM-Nanomedicine), Vall d'Hebron Institut de Recerca, and Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain.
authors: Simó
authors: S
authors: Schwartz
authors: Universidade de Lisboa, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Av. Professor Gama Pinto, 1649-004 Portugal. Electronic address: mvideira@ff.ul.pt.
authors: Mafalda A
authors: MA
authors: Videira
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004075:Diglycerides; D011092:Polyethylene Glycols; C009032:precirol; D017239:Paclitaxel
keywords: Intracellular delivery; Nanomedicines; PEGylation; Paclitaxel; Solid lipid nanoparticles