RESUMO
Photodynamic therapy (PDT) is a clinical treatment based on the activation of light-absorbing photosensitizers (PS) to generate reactive oxygen species, which are toxic to the targeted disease cells. Because most PS are hydrophobic with poor water solubility, it is necessary to encapsulate and solubilize PS in aqueous conditions to improve the photodynamic action for this compound. In this work, gelatin-poly(acrylic acid) nanoparticles (PAA/gelatin nanoparticles) via template polymerization for incorporation aluminum chloride phthalocyanine (ClAlPc) as a model drug for PDT application were developed. Biocompatible core-shell polymeric nanoparticles were fabricated via template polymerization using gelatin and acrylic acid as a reaction system. The nanoparticulate system was studied by scanning electron microscopy, steady-state, and their biological activity was evaluated using in vitro cancer cell lines by classical MTT assay. The obtained nanoparticles had a spherical shape and DLS particle size were determined further and was found to be around 170 nm. The phthalocyanine-loaded-nanoparticles maintained their photophysical behaviour after encapsulation. It is found that ClAlPc can be released from the nanoparticles in a sustained manner with a small initial burst release. In vitro cytotoxicity revealed that ClAlPc-loaded nanoparticles had similar cytotoxicity to free ClAlPc with mouse melanoma cancer cell line (B16-F10). In vitro photoeffects assay indicated that the nanoparticle formulation was superior in anticancer effect to free ClAlPc on mouse melanoma cancer cell line B16-F10. The results indicate that ClAlPc encapsulated in gelatin-poly(acrylic acid) nanoparticles are a successful delivery system for improving photodynamic activity in the target tissue.
Assuntos
Melanoma , Nanopartículas , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Gelatina , Camundongos , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , PolimerizaçãoRESUMO
Development delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (NP) were prepared using a double-emulsion method to load zinc(II) phthalocyanine (ZnPc). NP were obtained using poly (lactic acid) (PLA). ZnPc is a second generation of photosensitizer used in photodynamic therapy (PDT). ZnPc loaded PLA nanoparticles (NPLA-ZnPc) were prepared by double-emulsion method, characterized and available in cellular culture. The mean nanoparticle size presented particle size was 384.7 ± 84.2 nm with polydispersity index (PDI) of 0.150 ± 0.015, and the encapsulation efficiency was of 83%. The nanoparticle formulations presented negative zeta potential values (-27.5 ± 1.0 mV), explaining their colloidal stability. ZnPc loaded nanoparticles maintain its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained over 168 h with a biphasic ZnPc release profile. An in vitro phototoxic effect in range of 80% was observed in 9 L/LacZ gliosarcoma cells at laser light doses (10 J cm-2) with 3.0 µg mL-1 of NPLA-ZnPc. All the physical-chemical, photophysical and photobiological measurements performed allow us to conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for PDT.
Assuntos
Gliossarcoma , Nanopartículas , Compostos Organometálicos , Fotoquimioterapia , Emulsões , Humanos , Óperon Lac , Ácido Láctico , Fármacos Fotossensibilizantes , Poliésteres , Zinco , Compostos de ZincoRESUMO
BACKGROUND: Photodynamic Therapy (PDT) is a modality for the treatment of neoplastic tissues, which is based on the administration of a phototherapeutic agent and light irradiation at an appropriate wavelength, aiming to locate and destroy the target cell with the formation of reactive oxygen species. Nanoencapsulation technology presents itself as a tool for incorporation of bioactive substances aiming to improve their solubility in physiological environment, obtain a longer circulation time in the organism, administration of lower dosages and the minimization of side effects. The present work aimed at the development of poly (lactic acid-glycolic acid) (PLGA) nanoparticles coated with polyelectrolyte film layers for encapsulating zinc phthalocyanine tetrasulfonated (ZnPcSO4) as a bioactive substance model. METHODS: PLGA nanoparticles were produced by the double emulsion/solvent evaporation technique and polyelectrolytic coating was performed using polyalkylamine hydrochloride (PAH) as a weak polycation and poly (4-styrene sulfonate) (PSS) as a strong polyanion by layer-by-layer self-assembly technique (known as layer-by-layer-LbL). The nanoparticulate system was studied by scanning electron microscopy, steady-state, and their biological activity was evaluated using in vitro cancer cell lines by classical MTT assay. RESULTS: The polyelectrolytic PLGA nanoparticles had an average diameter of 384.7 ± 138.6 nm, restricted distribution size with a polydispersity index. The obvious change in zeta potential indicates successful alternation in polycation (PAH) and polyanion (PSS) deposition directly in PLGA nanoparticles. Scanning electron microscopy (SEM) analysis showed that the formed system had morphology spherical, typical of these release systems. The loading efficiency was 82.1 % ± 1.2 %. The polyelectrolytic nanoparticles loaded with phthalocyanine maintained their photophysical behavior after encapsulation. Cell viability was determined, obtaining 90 % cell death. CONCLUSIONS: Therefore, the presented work depicts ZnPcSO4-loaded polyelectrolytic PLGA nanoparticles as a promise drug delivery system for phototherapeutic agent, which are thus expected to have superior therapeutic efficiency than free drug.
Assuntos
Nanopartículas , Fotoquimioterapia , Portadores de Fármacos , Indóis , Ácido Láctico , Compostos Organometálicos , Tamanho da Partícula , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polieletrólitos , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
It has been demonstrated an increase in resistance of Candida albicans to conventional therapies, probably, due the indiscriminate use of the conventional antifungal drugs. In this aspect, the nanotechnology generates the possibility of creating new therapeutic agents. Thus, the objective of this paper was to produce and characterize a bovine serum albumin (BSA) nanoparticle encapsulated with Methylene Blue (MB). In addition, the effect of BSA nanoparticles encapsulated with MB (BSA-MB) was evaluated on both growth and biofilm formation by C. albicans by Photodynamic Antimicrobial Chemotherapy (PACT) protocols. The BSA-MB nanoparticles were prepared by the desolvation process. The nanoparticulate system was studied by steady-state techniques, scanning electron microscopy and their biological activity was evaluated in vitro both growth and biofilm formation by C. albicans. The synthetized BSA-MB nanoparticles were spherical in shape exhibiting a 100-200 nm diameter with a low tendency to aggregate (PDI values < 0.2). MB photophysical properties were shown to be preserved after BSA encapsulation. A significant reduction in C. albicans growth, after PACT was observed, in a dependent manner on MB-loaded in BSA nanoparticles concentration used. It was observed an inhibition of 23, 65 and 83% in the presence of MB-loaded in BSA nanoparticles 0.1, 0.5 and 1.0 µg.mL-1, respectively. In addition, MB-loaded BSA nanoparticles 0.5 µg.mL-1 were able to reduce both biofilm formation (80%) and the transition from yeast to filamentous form by C. albicans. The results presented here demonstrated a potentiation of the phototoxic effect of MB after BSA encapsulation, since the concentrations of MB-loaded BSA nanoparticles necessary to inhibits â¼50% of C. albicans development was 10 times minor than that observed for free MB. Taken together, these results suggest the potential of PACT, using MB-loaded BSA nanoparticles in inhibiting C. albicans development. The synthesis and design of BSA nanoparticles can be successfully applied for MB encapsulation and offer the possibility to drive the toxicity effect to a specific target, as an evaluation on both growth and biofilm formation by Candida albicans.
Assuntos
Anti-Infecciosos , Nanopartículas , Fotoquimioterapia , Antifúngicos/farmacologia , Biofilmes , Candida albicans , Azul de Metileno/farmacologia , Fármacos Fotossensibilizantes , Soroalbumina BovinaRESUMO
Recently several scientific-technological advances in the health area have developed. Among them, we can highlight research addressing nanoscience and nanotechnology focusing on the development of formulations for the cancer treatment. This work describes the synthesis and characterization of bovine serum albumin (BSA) polyelectrolytic nanoparticles for controlled release using silicon dihydroxide phthalocyanine [SiPc (OH)2] as a photosensitizer model for application in Photodynamic Therapy (PDT). BSA nanoparticles were prepared by the one-step desolvation process and the nanoparticulate system was coated with polyelectrolytes using poly-(4-styrene sulfonate - PSS) as a strong polyanion and polyallylamine hydrochloride (PAH) as a weak polycation by the technique self-assembling layer-by-layer (LbL). The formulation was characterized and available in cellular culture. The profile of drug release was investigated and compared to that of free [SiPc (OH)2]. The nanoparticles have a mean diameter of 226.9 nm, a narrow size distribution with polydispersive index of 0.153, smooth surface and spherical shape. [SiPc(OH)2] loaded nanoparticles maintain its photophysical behaviour after encapsulation. The polyelectrolytic nanoparticles improved efficiency in release and photocytotoxicity assay when compared to pure drug. The results demonstrate that photosensitizer adsorption on BSA nanoparticles together with biopolymer layer-by-layer assembly provides a way to manufacture biocompatible nanostructured materials that are intended for use as biomaterials for Photodynamic Therapy applications.
Assuntos
Nanopartículas , Fotoquimioterapia , Sistemas de Liberação de Medicamentos , Isoindóis , Tamanho da Partícula , Polieletrólitos , Soroalbumina Bovina , SilícioRESUMO
Gelatin nanoparticles (GN) with an intrinsic antimicrobial activity maybe a good choice to improve the effectiveness of photodynamic antimicrobial chemotherapy (PACT). The aim of this study was to development gelatin nanoparticles loaded methylene blue (GN-MB) and investigate the effect of GN-MB in the Candida albicans growth by PACT protocols. The GN and GN-MB were prepared by two-step desolvation. The nanoparticulate systems were studied by scanning electron microscopy and steady-state techniques, the in vitro drug release was investigated, and we studied the effect of PACT on C. albicans growth. Satisfactory yields and encapsulation efficiency of GN-MB were obtained (yield = 76.0% ± 2.1 and EE = 84.0% ± 1.3). All the spectroscopic results presented here showed excellent photophysical parameters of the studied drug. Entrapment of MB in GN significantly prolongs it's in vitro release. The results of PACT experiments clearly demonstrated that the photosensitivity of C. albicans was higher when GN-MB was used. Gelatin nanoparticles loaded methylene blue-mediated photodynamic antimicrobial chemotherapy may be used against Candida albicans growth.