RESUMEN
Poly(lactide-co-glycolide) (PLGA) has been used for the encapsulation of phthalocyanine motived by its biocompatibility and biodegradability. Many studies have already been done to evaluate the influence of parameters used in the PLGA nanoparticle synthesis but without the evaluation of the combinatory interaction between these parameters on the nanoparticulate properties. Ga(III)-phthalocyanine (GaPc) was encapsulated into the PEGlated PLGA-nanoparticles and the individual and combinatory effects of the emulsification time, the method used for the nanoparticle synthesis and the temperature of the aqueous phase was evaluated on the size, entrapment efficiency, efficacy of nanoparticle recovery, residual PVA and zeta potential value using a 23 factorial design (FD). Mathematical models were adjustable to the data and evolutionary operations were performed to optimize the nanoparticle size. The ability of the optimized nanoparticle to decrease the viability of the Hepa-1C1C7 cell and the blood red cell was also evaluated. The FD disclosed the emulsification-diffusion method decreased the residual PVA and the size of PLGA-PEG nanoparticle, but also decreased the entrapment efficiency of GaPc, the zeta potential absolute value and the recovery efficacy of nanoparticles. The combinatory effect between the method used in the nanoparticle preparation and the temperature of aqueous phase influenced four of the five evaluated properties. The viability of Hepa-1C1C7 cells was reduced until 13× when the cells were irradiated in the presence of encapsulated GaPc while it was decreased until 4.7× when the experiment was carried out with the free GaPc. The encapsulated GaPc was also more efficient to cause the haemolysis of the RBC than it was the free GaPc. The optimization of the nanoparticles synthesis increased the efficiency of the GaPc to oxidize the evaluated cells.
Asunto(s)
Galio/química , Nanopartículas/química , Poliésteres/química , Polietilenglicoles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Hemólisis/efectos de los fármacos , Humanos , Indoles/química , Isoindoles , Nanopartículas/toxicidad , Tamaño de la Partícula , TemperaturaRESUMEN
The development and manufacture of novel nanocarriers for drug delivery has proved challenging with regards to scale-up and pharmaceutical quality. Polymeric nanocarriers composed of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) were prepared and the photosensitizer meso-tetrakis(3-hydroxyphenyl) chlorin (mTHPC) was effectively encapsulated. Furthermore, the interplay of various process and formulation parameters and their impact on the most important product specifications were investigated by using a factorial design and a central composite design in a microfluidic manufacturing process. These nanoparticles for intravenous administration with a size of 97 ± 0.13 nm, narrow size distribution, and an encapsulation efficiency of more than 80% were produced at high throughput. In vitro stability and in vitro drug release testing were applied for quality control purposes. Finally, the toxicity of the photosensitizer was tested in vitro. The cytotoxicity was successfully reduced while the efficacy of the formulation was maintained. First observations using in vivo imaging suggest effective distribution of the nanocarrier system after injection into rodents. Thus, further in vivo testing of the beneficial effects of nanoencapsulation into the matrix system and its formulation will be considered for the delivery of mTHPC to tumor tissues during photodynamic therapy.