RESUMO
Recently, synthetic polymers have attracted great interest in the field of biomedical science. Among these, polyphosphazenes (PPZs) are regarded as one of the most promising materials, due to their structural flexibility and biodegradability compared to other materials. PPZs have been developed through numerous studies. In particular, multi-functionalized PPZs have been proven to be potential biomaterials in various forms, such as nanoparticles (NPs) and hydrogels, through the introduction of various functional groups. Thus, PPZs have been applied for the delivery of therapeutic molecules (low molecular weight drugs, genes and proteins), bioimaging, phototherapy, bone regeneration, dental liners, modifiers and medical devices. The main goal of the present review is to highlight the recent and the most notable existing PPZ-based biomaterials for aforementioned applications, with future perspectives in mind.
Assuntos
Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Polímeros/uso terapêutico , Polímeros/química , Compostos Organofosforados/uso terapêutico , Compostos Organofosforados/químicaRESUMO
To date, cancer therapies largely consist of five pillars: surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. Still, researchers are trying to innovate the current cancer therapies to pursue an ideal one without side effects. For developing such a therapy, we designed a chemically well-defined route to a PEG- and docetaxel (DTX)-conjugated inorganic polymer, polyphosphazene, named "polytaxel (PTX)" with a prolonged blood circulation time and tumor localization. Here, we conducted the proof-of-concept study of the ideal therapy in orthotopic and xenograft pancreatic cancer models. We found that the average tumor inhibition rates of PTX were similar to those of DTX without any DTX toxicity-related side effects, such as neutropenia and weight loss. In conclusion, PTX met the requirements of an ideal anticancer drug with high anticancer efficacy and 100% survival rate. PTX is expected to replace any existing anticancer therapies in clinical practice.
Assuntos
Neutropenia , Neoplasias Pancreáticas , Humanos , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Nível de Efeito Adverso não Observado , Taxoides/efeitos adversos , Polímeros/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológicoRESUMO
We synthesized biodegradable b-PEIS (branched poly(ethylenimine sulfide)) by crosslinking linear PEIS. We controlled the degree of crosslinking and molecular weight by adjusting the amount of the crosslinker, bisepoxide. The b-PEIS was readily degradable under reductive conditions (5mm glutathione solution) and the degradation time was dependent on the degree of crosslinking. We controlled the molecular weights of the b-PEIS by regulating the amount of crosslinker and thus, the degree of crosslinking. Our titration data showed that there was almost no loss in buffering ability before or after bisepoxide crosslinking. We verified the degradation of this polymer by MALLS and gel electrophoresis, and confirmed that there was a high transfection efficiency and low cytotoxicity based on cellular data. Intracellular trafficking was observed by image restoration microscopy, demonstrating that b-PEIS does not accumulate in the cell interior.
Assuntos
Implantes Absorvíveis , DNA/administração & dosagem , DNA/farmacocinética , Portadores de Fármacos/química , Células Endoteliais/fisiologia , Marcação de Genes/métodos , Polietilenoimina/química , Sulfetos/química , Transfecção/métodos , Células Cultivadas , DNA/genética , Humanos , Teste de MateriaisRESUMO
We developed a polyethylene glycol (PEG)-based biodegradable hydrogel through disulfide crosslinking of polyethylene oxide sulfide (PEOS). The crosslinking rate was highly dependent on temperature, and incubation at about 40-50 degrees C was required for efficient crosslinking. The crosslinked PEOS hydrogel showed glutathione-dependent dissolution and corresponding controlled release of a model drug-fluorescein isothiocyanate (FITC)-labeled dextran-because the disulfide bond, the main linker, is selectively degraded in response to the high concentration of glutathione. The temperature-sensitive crosslinking and the hydrogel formation have the potential for use as an injectable biogel precursor, which was confirmed by in situ gel formation in mice.
Assuntos
Dextranos/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Polietilenoglicóis/química , Sulfetos/química , Animais , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Fluoresceína-5-Isotiocianato/administração & dosagem , Glutationa/metabolismo , Hidrogéis , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C57BL , TemperaturaRESUMO
Poly(ethylene oxide sulfide) (PEOS), polymers consisting of an internal ethylene oxide oligomer and disulfide linkage, were synthesized and characterized. The degree of polymerization was dependent upon temperature, dimethyl sulfoxide condition, and monomer hydrophobicity. The stability of PEOS was measured by the size exclusion chromatography method after the incubation both with and without 5 mM glutathione. The disulfide bond was stable in the extracellular condition but completely degraded in 2 h in the reductive cytosolic condition. Hydrophilic PEOS polymers showed no cytotoxicity on the HepG2 cell line. On the basis of these properties, PEOS can be applied in many drug delivery fields.