title: Improved photodynamic activity of porphyrin loaded into nanoparticles: an in vivo evaluation using chick embryos.
abstract: Hydrophobic porphyrins are potentially interesting molecules for the photodynamic therapy (PDT) of solid cancers or ocular vascularization diseases. Their pharmaceutical development is, however, hampered by their lipophilicity, which renders formulation difficult especially when intravenous administration is needed. Encapsulation of a lipophilic derivative of porphyrin, the meso-tetra(p-hydroxyphenyl)porphyrin (p-THPP), into polymeric biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles proved to enhance its photodynamic activity against mammary tumour cells when compared to free drug. In order to further investigate these carriers, the efficacy of the encapsulated drug was assessed on the chick embryo chorioallantoic membrane (CAM) model. First, we identified a suitable solvent for the drug in terms of p-THPP solubility and tolerability by chick embryos. This solution was used as a reference. Then, the fluorescence pharmacokinetics and the photodynamic effects of the porphyrin on CAM vessels were evaluated after intravenous administration of either a p-THPP solution (free drug) or the drug loaded into nanoparticles. The results showed that: (i) the drug remained longer in the vascular compartment when incorporated into nanoparticles and (ii) vascular effects of p-THPP after light irradiation were enhanced with nanoparticle carriers. These results are discussed taking into account the extravasation of intravascular circulating photosensitizers and its influence on PDT performance.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, School of Pharmacy, University of Geneva, 30, quai E. Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Angelica
authors.initials: A
authors.lastname: Vargas
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pegaz
authors.forename: Elodie
authors.initials: E
authors.lastname: Debefve
authors.forename: Yvette
authors.initials: Y
authors.lastname: Konan-Kouakou
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ballini
authors.forename: Hubert
authors.initials: H
authors.lastname: van den Bergh
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.forename: Florence
authors.initials: F
authors.lastname: Delie
mesh_terms: D000818:Animals; D002642:Chick Embryo / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004357:Drug Synergism; D000431:Ethanol / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control; D005453:Fluorescence; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012995:Solubility; D013557:Switzerland
chemical_list: D004338:Drug Combinations; D019999:Pharmaceutical Solutions; D017319:Photosensitizing Agents; D011108:Polymers; D011166:Porphyrins; C481734:meso-tetra-(4-hydroxyphenyl)porphyrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000431:Ethanol