title: Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation.
abstract: OBJECTIVE
  To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation.
  
  
  METHODS
  Micelles of mPEG750-b-oligo(epsilon-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg).
  
  
  RESULTS
  Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30% (w/w), likely due to pi-pi interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored.
  
  
  CONCLUSIONS
  The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB, Utrecht, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Hofman
authors.forename: Myrra G
authors.initials: MG
authors.lastname: Carstens
authors.forename: Femke
authors.initials: F
authors.lastname: van Zeeland
authors.forename: Conny
authors.initials: C
authors.lastname: Helwig
authors.forename: Frits M
authors.initials: FM
authors.lastname: Flesch
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
mesh_terms: D002208:Caproates / Q000737:chemistry* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism; D008049:Lipase / Q000378:metabolism*; D008081:Liposomes; D008652:Mesoporphyrins / Q000737:chemistry / Q000494:pharmacology*; D008823:Micelles; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002208:Caproates; D007783:Lactones; D008081:Liposomes; D008652:Mesoporphyrins; D008823:Micelles; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C121056:caprolactone; C028210:monomethoxypolyethylene glycol; D008049:Lipase; C072269:temoporfin