Distribution of photosensitizers in bladder cancer spheroids: implications for intravesical instillation of photosensitizers for photodynamic therapy of bladder cancer.
J Pharm Pharm Sci
; 8(3): 536-43, 2005 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-16401399
ABSTRACT
PURPOSE:
Uniform intratumor distribution of sufficient photosensitizer is one of the important aspects of photodynamic therapy for solid tumors.METHODS:
Multicellular spheroids derived from a human transitional cell carcinoma cell line (MGHU3) were used as a surrogate system of tiny solid tumors to study intratumor distribution of photosensitizers. Photosensitizers included Photofrin, hypocrellins (HBEA-R1/R2, HBBA-R2), aluminum phthalocyanine chloride (AlPC), benzoporphyrin derivative monoacid ring A (BPD-MA), protoporphyrin-IX (PpIX), and liposomal formulations of HBBA-R2 and BPD-MA. Spheroids were incubated with various doses of the above drugs for 1-4 hours, and were examined by confocal microscopy.RESULTS:
Histology showed all cells were healthy in spheroids less than 400 microm in diameter. Scanning electron microscopy showed tight cell-to-cell interdigitation in spheroids. HBEA-R1/R2 distributed more uniformly in spheroids than other drugs. Free hypocrellins and BPD-MA penetrated spheroids centripetally deeper than AlPC, Photofrin, and PpIX. Liposomal HBBA-R2 and BPD-MA penetrated less than their free formulations.CONCLUSIONS:
The spheroids mimic solid tumors prior to neovascularization. Based on drug distribution in spheroids, hypocrellins and BPD-MA appear superior to Photofrin, AlPC and PpIX for intravesical administration for bladder cancer phototherapy.
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Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Neoplasias da Bexiga Urinária
/
Fármacos Fotossensibilizantes
/
Esferoides Celulares
Limite:
Humans
Idioma:
En
Revista:
J Pharm Pharm Sci
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Canadá