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Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy

European Journal of Pharmaceutics and Biopharmaceutics
Publication Date
DOI: 10.1016/s0939-6411(02)00128-5
  • Nanoparticles
  • Poly(D
  • L-Lactide)
  • Poly(D
  • L-Lactide-Co-Glycolide)
  • Sterile Filtration
  • Photosensitizer
  • Meso-Tetra(P-Hydroxyphenyl)Porphyrin
  • P-Thpp


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 μm membranes. The three selected polyesters (poly( d, l-lactide-co-glycolide), (50:50 PLGA, 75:25 PLGA) and poly( d, l-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 drug loading was investigated in terms of particle size, drug 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 drug loading. After purification by cross-flow filtration, the nanoparticle suspensions were sterilized by membrane filtration and freeze-dried in the presence of a lyoprotectant (trehalose). For all types of nanoparticles, complete redispersion in various media could be obtained. All final freeze-dried products were refiltrable on a 0.22 μm membrane and were stable in terms of mean particle size and drug loading over a period up to 6 months. The effective drug loading increased at higher theoretical drug loading, the entrapment efficiency was however decreased. The same trend was observed with the three polyesters. The sterility of the final freeze-dried nanoparticles was confirmed by the results of the sterility testing which showed no bacterial contamination.

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