title: Benefits of nanoencapsulation for the hypercin-mediated photodetection of ovarian micrometastases.
abstract: The high recurrence and lethality of ovarian cancer at advanced stages is problematic, especially due to the development of numerous micrometastases scattered throughout the abdominal cavity. Fluorescence photodetection (PD) used in combination with surgical resection of malignant tissues has been suggested to improve recovery. Based on promising in vivo results for the detection of bladder cancer, hypericin (Hy), a natural photosensitizer (PS), stands as a good candidate for the photodetection of ovarian cancer. However, due to its hydrophobicity, systemic administration of Hy is problematic. Polymeric nanoparticles (NPs) help to overcome these delivery and stability problems and enable intravenous administration of Hy. In this study, Hy-loaded NPs of polylactic acid were produced with the following properties: (i) mean size of 268 nm, (ii) negative zeta potential, (iii) low residual surfactant and (iv) drug loading of 3.7 % (w/w). The potential of hypericin-loaded nanoparticles for the fluorescence photodetection of ovarian metastases in Fischer 344 rats bearing ovarian tumours was compared to free drug. The selectivity of Hy administered with both formulations was assessed first by fluorescence endoscopy, and then quantified after tissue extraction. The results showed an improved selective accumulation of Hy in ovarian micrometastases when NPs were used.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Magali
authors.initials: M
authors.lastname: Zeisser-Labouèbe
authors.forename: Florence
authors.initials: F
authors.lastname: Delie
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
mesh_terms: D000818:Animals; D000873:Anthracenes; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004724:Endoscopy; D005260:Female; D005453:Fluorescence; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D010569:Perylene; C004965:hypericin