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1.
Eur J Pharm Biopharm ; 157: 38-46, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33059005

RESUMO

The spread of a primary malignant tumor is the major reason for most of the cancer-associated deaths. To this day, treatment regimen and available drugs are still insufficient to manage these conditions. In this work, a new therapeutic concept based on photodynamic therapy (PDT) of metastasis-initiating cells is introduced. To address this issue, an experimental model was developed to simulate the movement and photodynamic inactivation of circulating tumor cells (CTCs) in vitro. Using curcumin loaded poly(lactic-co-glycolic acid) nanoparticles, a significant reduction in the cell viability of human breast cancer cells (MDA-MB-231) could be achieved after 30 min laser irradiation (λ = 447 nm, P = 100mW) under flow conditions (5 cm s-1). Confocal laser scanning microscopy images confirmed the immediate accumulation of curcumin on the cell membrane and an increased fluorescence signal after irradiation. PDT caused time-dependent morphological cell alterations (i.e. membrane evaginations and disruption) indicating apoptosis and early necrosis. During the photoactivation of curcumin, a blue shift in the absorption spectra and a decrease in the curcumin content could be determined. This study confirms that the presented experimental model is suitable for in vitro investigations of CTCs under in vivo-like conditions, at the same time encouraging the clinical implementation of PDT as an innovative strategy against metastasis.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/ultraestrutura , Linhagem Celular Tumoral , Curcumina/química , Portadores de Fármacos , Composição de Medicamentos , Feminino , Humanos , Microscopia Confocal , Microscopia Eletroquímica de Varredura , Nanopartículas , Necrose , Metástase Neoplásica , Células Neoplásicas Circulantes/ultraestrutura , Fármacos Fotossensibilizantes/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
2.
Eur J Pharm Biopharm ; 139: 59-67, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30836179

RESUMO

Nanostructured coatings of dental implants have shown great potential in overcoming many challenges responsible for implant failure. In this study, nano spray drying technology was utilized to produce novel biocompatible nanocoatings with antibacterial activity. The experiments were applied on titanium discs, which were used as a model material for dental implants. The produced nanocoatings consisted of poly(lactic-co-glycolic acid) as a biodegradable polymer and norfloxacin as a model antibiotic. Scanning electron microscopy results revealed an average particle size ranging between 400 and 600 nm. In vitro release studies showed a biphasic drug release profile with a burst release within the first 48 h, followed by a sustained release phase until the end of the experiment. The antibacterial activity of the nanocoatings was evaluated against Escherichia coli where the norfloxacin loaded nanocoatings achieved up to 99.83% reduction in the number of viable bacterial colonies. Finally, in vitro biocompatibility of the nanocoatings was investigated using mouse fibroblasts (L929) as a standard sensitive cell line for cytotoxicity assessment. Cell proliferation on the surface of the titanium discs was studied using fluorescence microscopy followed by cell counting assay. Both methods confirmed the biocompatibility of the examined nanocoatings. In conclusion, nano spray drying is a promising technique for preparing tailor-made nanocoatings, thereby representing an innovative approach for the surface modification of dental implants.


Assuntos
Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Implantes Dentários , Nanoestruturas/química , Animais , Antibacterianos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos , Teste de Materiais/métodos , Camundongos , Microscopia Eletrônica de Varredura , Nanoestruturas/ultraestrutura , Norfloxacino/química , Norfloxacino/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Propriedades de Superfície , Titânio
3.
Photochem Photobiol Sci ; 18(2): 304-308, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30620037

RESUMO

Photodynamic therapy is one of the most promising non-invasive strategies employed for the treatment of several kinds of bacterial infections. Though the vast majority of clinically approved photosensitisers are administered intravenously, most of the in vitro experiments are performed under static conditions which do not represent the physiological environment of the venous bloodstream. To address this issue, a dynamic circulation model was developed to facilitate in situ antibacterial photodynamic therapy under flow conditions to mimic blood stream infections.


Assuntos
Bacteriemia/tratamento farmacológico , Fotoquimioterapia/métodos , Humanos , Teste de Materiais , Nanopartículas/efeitos adversos , Nanopartículas/química
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