Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy.
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 microm 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 microm 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.
Konan
Yvette Niamien
YN
School of Pharmacy, University of Geneva, Geneva, Switzerland.
Cerny
Radovan
R
Favet
Joselyne
J
Berton
Myriam
M
Gurny
Robert
R
Allémann
Eric
E
D004655:Emulsions / Q000737:chemistry; D005374:Filtration; D005612:Freeze Drying; D019344:Lactic Acid / Q000737:chemistry; D008970:Molecular Weight; D036103:Nanotechnology; D010316:Particle Size; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry*; D015203:Reproducibility of Results; D013242:Sterilization; D013499:Surface Properties; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D004655:Emulsions; D017319:Photosensitizing Agents; D011091:Polyesters; D011108:Polymers; D011166:Porphyrins; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); C051232:5,10,15,20-tetra(4-hydroxyphenyl)porphyrin