Effect of delivery system on the pharmacokinetic and phototherapeutic properties of bis(methyloxyethyleneoxy) silicon-phthalocyanine in tumor-bearing mice.

A Si(IV)-phthalocyanine bearing two methoxyethyleneglycol axial ligands bound to the central metal ion (SiPc) has been prepared by chemical synthesis and analyzed for its phototherapeutic activity after administration in a Cremophor or liposome formulation to C57B1/6 mice bearing a subcutaneously transplanted Lewis lung carcinoma (LLC). The maximum drug accumulation in the tumor is found at 24 h after intraperitoneal injection, independent of the delivery system. However, the tumor concentration of SiPc in the Cremophor formulation is about two-fold higher, while the drug concentration in liver and skin shows similar trends with the two delivery systems. The drug accumulation and retention in the brain is much larger when using Cremophor emulsion. Photodynamic therapy (672 nm, 370 mW m-2, 360 J cm-2) at 24 h after the injection of Cremophor emulsion- or DPPC liposome-formulated SiPc causes a very efficient and similar response for the LLC (approximately 8 versus 22 mm mean tumor diameter for the control groups at 21 days after phototreatment). These very promising effects, obtained both at higher and lower tumor drug concentrations, clearly demonstrate the potential phototherapeutical activity of the newly synthesized SiPc.

Si(IV)-methoxyethylene-glycol-naphthalocyanine: synthesis and pharmacokinetic and photosensitizing properties in different tumour models.

A Si(IV)-naphthalocyanine bearing two methoxyethylenglycol axial ligands to the centrally coordinated metal ion (SiNc) was prepared by chemical synthesis and assayed for the phototherapeutic activity after administration in a Cremophor formulation to C57BI/6 mice bearing a subcutaneously transplanted Lewis lung carcinoma or B16 pigmented melanoma. Pharmacokinetic studies indicate that the maximal accumulation in the tumour occurs at 24 h after intraperitoneal injection of 0.5 mg kg-1 of SiNc, although the naphthalocyanine concentration in the Lewis lung carcinoma (0.70 microgram g-1) is significantly larger than that in the B16 pigmented melanoma (0.15 microgram g-1). This results in a higher selectivity of tumour targeting in the case of the lung carcinoma. Photodynamic therapy (782 nm, 370 mW cm-2, 360 J cm-2) at 24 h after SiNc injection causes an efficient tumour response for Lewis lung carcinoma (50% lower tumour diameter on day 19 post-treatment as compared to untreated controls) while the pigmented melanoma shows only a minor response regarding the rate of tumour growth.