Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation.
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.
Hofman
Jan-Willem
JW
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB, Utrecht, The Netherlands.
Carstens
Myrra G
MG
van Zeeland
Femke
F
Helwig
Conny
C
Flesch
Frits M
FM
Hennink
Wim E
WE
van Nostrum
Cornelus F
CF
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
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