Enhanced photodynamic activity of meso-tetra(4-hydroxyphenyl)porphyrin by incorporation into sub-200 nm nanoparticles.
A photosensitizer, meso-tetra(hydroxyphenyl)porphyrin (p-THPP) was incorporated into sterile submicronic nanoparticles of poly(D,L-lactide-co-glycolide) (50:50 and 75:25 PLGA) and poly(D,L-lactide) (PLA). With all polymers used, sub-130 nm p-THPP-loaded nanoparticles with similar drug loadings and entrapment efficiencies were produced using the emulsification-diffusion technique. The photodynamic activity (photocytotoxicity) of these nanoparticles was evaluated on EMT-6 mammary tumour cells in comparison with the free drug. The influence of drug concentration (3-10 microg/ml), incubation time (5-60 min) and light dose (6-9 J/cm(2)) on p-THPP photocytotoxic efficiency was investigated. With all p-THPP formulations tested, cell viability decreased with increasing values of these parameters. The beneficial effect of nanoencapsulation compared to free drug was highlighted at drug concentrations up to 6 microg/ml and short incubation times (15-30 min). The most important photocytotoxicity was observed with 50:50 PLGA nanoparticles allowing low drug doses and short drug administration-irradiation intervals for local photodynamic therapy.
Konan
Yvette Niamien
YN
School of Pharmacy, University of Geneva, 30 quai E. Ansermet, CH-1211 4, Geneva, Switzerland.
Berton
Myriam
M
Gurny
Robert
R
Allémann
Eric
E
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D043942:Nanotubes; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry
D017319:Photosensitizing Agents; D011108:Polymers; D011166:Porphyrins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C051232:5,10,15,20-tetra(4-hydroxyphenyl)porphyrin