ABSTRACT
Photodynamic therapy (PDT) mediated by photosensitizers loaded in nanostructures as solid lipid nanoparticles has been pinpointed as an effective and safe treatment against different skin cancers. Amazon butters have an interesting lipid composition when it comes to forming solid lipid nanoparticles (SLN). In the present report, a new third-generation photosensitizing system consisting of aluminum-phthalocyanine associated with Amazon butter-based solid lipid nanoparticles (SLN-AlPc) is described. The SLN was developed using murumuru butter, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 40 nm was obtained. The study of the permeation of these AlPc did not permeate the analyzed skin, but when incorporated into the system, SLN-AlPc allowed permeation of almost 100% with 8 h of contact. It must be emphasized that SLN-AlPc was efficient for carrying aluminum-phthalocyanine photosensitizers and exhibited no toxicity in the dark. Photoactivated SLN-AlPc exhibited a 50% cytotoxicity concentration (IC50) of 19.62 nM when applied to B16-F10 monolayers, and the type of death caused by the treatment was apoptosis. The exposed phospholipid phosphatidylserine was identified, and the treatment triggered a high expression of Caspase 3. A stable Amazon butter-based SLN-AlPc formulation was developed, which exhibits strong in vitro photodynamic activity on melanoma cells.
ABSTRACT
Nanocapsules (NCS-DOX) with an oily core of selol and a shell of poly(methyl vinyl ether-co-maleic anhydride) covalently conjugated to doxorubicin were developed. These nanocapsules are spherical, with an average hydrodynamic diameter of about 170 nm, and with negative zeta potential. NCS-DOX effectively co-delivered the selol and the doxorubicin into 4T1 cells and changed the intracellular distribution of DOX from the nuclei to the mitochondria. Moreover, a significantly increased cytotoxicity against 4T1 cells was observed, which is suggestive of additive or synergic effect of selol and doxorubicin. In conclusion, PVM/MA nanocapsules are suitable platforms to co-deliver drugs into cancer cells.
Subject(s)
Adenocarcinoma/drug therapy , Doxorubicin , Mammary Neoplasms, Animal/drug therapy , Nanocapsules , Selenium Compounds , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Nucleus/pathology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Female , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Animal/pathology , Mice , Mitochondria/metabolism , Mitochondria/pathology , NIH 3T3 Cells , Nanocapsules/chemistry , Nanocapsules/therapeutic use , Selenium Compounds/chemistry , Selenium Compounds/pharmacokinetics , Selenium Compounds/pharmacologyABSTRACT
This study describes the synthesis of magnetic nanohydrogels by miniemulsion polymerization technique. Dextran was derivatized by the glycidyl methacrylate to anchor vinyl groups on polysaccharides backbone, allowing its use as a macromonomer for miniemulsion polymerization, as confirmed by proton nuclear magnetic resonance spectroscopy (13C NMR). Magnetite nanoparticles were synthesized by coprecipitation, followed by air oxidation to maghemite. The results of X-ray diffractometry (XRD), Raman and transmission electron microscopy (TEM) analysis showed that maghemite nanoparticles were obtained with a diameter of 5.27nm. The entrapment of iron oxide nanoparticles in a dextran nanohydrogel matrix was confirmed by thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and Zeta potential data. The magnetic nanohydrogels presented superparamagnetic behavior and were colloidal stable in physiological during 30days. Our findings suggest that the synthesized magnetic nanohydrogel are potential candidates for use in drug delivery systems due to its physicochemical and magnetic properties.
ABSTRACT
BACKGROUND: Photodynamic therapy (PDT) combines light, molecular oxygen and a photosensitizer to induce oxidative stress in target cells. Certain hydrophobic photosensitizers, such as aluminium-phthalocyanine chloride (AlPc), have significant potential for antitumor PDT applications. However, hydrophobic molecules often require drug-delivery systems, such as nanostructures, to improve their pharmacokinetic properties and to prevent aggregation, which has a quenching effect on the photoemission properties in aqueous media. As a result, this work aims to develop and test the efficacy of an AlPc in the form of a nanoemulsion to enable its use in anticancer PDT. RESULTS: The nanoemulsion was developed using castor oil and Cremophor ELP®, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 25 nm was obtained. While free AlPc failed to show significant activity against human breast adenocarcinoma MCF-7 cells in an in vitro PDT assay, the AlPc in the nanoemulsion showed intense photodynamic activity. Photoactivated AlPc exhibited a 50 % cytotoxicity concentration (CC50) of 6.0 nM when applied to MCF-7 cell monolayers and exerted a powerful cytotoxic effect on MCF-7 cell spheroids. CONCLUSION: Through the use of spontaneous emulsification, a stable AlPc nanoemulsion was developed that exhibits strong in vitro photodynamic activity on cancer cells.
