<title>Pharmaceutical development of CGP 55847: a liposomal Zn-phthalocyanine formulation using a controlled organic solvent dilution method</title>

Abstract

Liposomes were prepared containing zinc-phthalocyanine (ZnPc). The composition was ZnPc/POPC/OOPS (1 :90:1 0 w/w 1w). The phospholipids (PL) were dissolved in t-butanol at 50°C under magnetic stirring and mixed with ZnPc, dissolved in NMP for two hours in an ultrasonic bath at 80 °C. This mixture (50°C) was diluted with lactose-NaCI solution (9.475 % lactose, 0.027% NaCl) at 4°C using a dynamic mixer. The collected liposomal suspension was concentrated first, to 20 mg PLiml suspension and then the organic solvents were removed by tangential flow filtration (CentrasetteR) against a ten fold volume of lactose-NaCl solution . After sterile filtration the liposomal suspension was freeze-dried for 24 hours. For preparation of the liposomal suspension, water for injection was added to the lyophilisate and shaken by hand after hydration for 60 5.

CGP 55398, a liposomal Ge(IV) phthalocyanine bearing two axially ligated cholesterol moieties: a new potential agent for photodynamic therapy of tumours

“…Melting point, 274-276°C; UV(CH2Cl2), 358 (63900), 678 (275700); PDMS, 1753.9 (M+); NMR (CDC13), 9.50 (m), 8.34 (m), 6.70 (t), 6.29 (t), 4.91 (d), 4.63 (m), 2.1-0 (remaining H atoms). The incorporation of Ge(IV) phthalocyanine into small unilamellar liposomes was performed by the same procedure as published for zinc(II) phthalocyanine-containing liposomes (Isele et al, 1993), with the exception that tetrahydrofuran was used as solvent for both the phthalocyanine derivative and the phospholipids. Liposomes were prepared from mixing of the phospholipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC, CGP 31 586) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (OOPS, CGP 31 524A) at a ratio of 9:1.…”

Can nanotechnology potentiate photodynamic therapy?

“…A second successful application of liposomes in PDT drug delivery was that of zinc(II) phthalocyanine (ZnPC; see Figure 2B). ZnPC is highly insoluble and was formulated by Ciba-Geigy Pharmaceuticals in liposomes composed of palmitoyl-oleoyl-phosphatidylcholine and di-oleoyl phosphatidylserine (ZnPC/OPOC/OOPS; 1:90:10 w/w/w) to form CGP55847 [14]. Although CGP55847 was tested in clinical trials of PDT for squamous cell carcinomas of the upper aerodigestive tract [15], it never received regulatory approval.…”

“…The MSN surface was post-functionalized with a mannose derivative to target lectins overexpressed by cancer cells [14]. Incubated with cancer cells, these MSNs were nontoxic under daylight illumination.…”

Can nanotechnology potentiate photodynamic therapy?

“…A second successful application of liposomes in PDT drug delivery was that of zinc(II) phthalocyanine (ZnPC; see Figure 2B). ZnPC is highly insoluble and was formulated by Ciba-Geigy Pharmaceuticals in liposomes composed of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl phosphatidylserine (ZnPC/OPOC/OOPS; 1:90:10 w/w/w) to form CGP55847 [14] . Although CGP55847 was tested in clinical trials of PDT for squamous cell carcinomas of the upper aerodigestive tract [15] , it never received regulatory approval.…”

“…The MSN surface was postfunctionalized with a mannose derivative to target lectins overexpressed by cancer cells [14] . Incubated with cancer cells, these MSNs were nontoxic under daylight illumination.…”