Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy
Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy
January 2003
Yvette Niamien Konan, Radovan Cerny, Joselyne Favet, Myriam Berton, Robert Gurny and Eric All?mann
European Journal of Pharmaceutics and Biopharmaceutics Volume 55, Issue 1 , January 2003, Pages 115-124
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Abstract
A photosensitizer, meso-tetra(4-hydroxyphenyl)porphyrin, was incorporated into sub-150 nm nanoparticles using the emulsification-diffusion technique in order to perform sterilization by filtration using 0.22 small mu, Greekm membranes. The three selected polyesters (poly(Image,Image-lactide-co-glycolide), (50:50 PLGA, 75:25 PLGA) and poly(Image,Image-lactide (PLA)) for the nanoparticle production were all amorphous in nature and have similar molecular weights but different copolymer molar ratios. The influence of the copolymer molar ratio and the theoretical drugnext term loading was investigated in terms of particle size, previous termdrugnext term loading, entrapment efficiency and surface characteristics. With all the polymers used, sub-150 nm nanoparticles were produced with good reproducibility and narrow size distributions irrespective of both the polymer nature and the theoretical previous termdrugnext term loading. After purification by cross-flow filtration, the nanoparticle suspensions were sterilized by membrane filtration and previous termfreeze-driednext term in the presence of a lyoprotectant (trehalose). For all types of nanoparticles, complete redispersion in various media could be obtained. All final previous termfreeze-driednext term products were refiltrable on a 0.22 small mu, Greekm membrane and were stable in terms of mean particle size and previous termdrugnext term loading over a period up to 6 months. The effective previous termdrugnext term loading increased at higher theoretical previous termdrugnext term loading, the entrapment efficiency was however decreased. The same trend was observed with the three polyesters. The sterility of the final previous termfreeze-driednext term nanoparticles was confirmed by the results of the sterility testing which showed no bacterial contamination.
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