Reaction #1121560

ord-b6425798170940428bd12f1d5331f419

Reaction equation

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin HCl
→
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin

Reactants

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin HCl

Reagents

None

Solvents

CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN.CS(=O)(=O)O
desferal

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.ADDITIONwas added to I ml of the liposome dispersion after the liposomes
  2. 2
    Filtrationfiltrated on a Sephadex G-50 column
  3. 3
    Otherin a 15 min
  4. 4
    workup.ADDITIONA column containing 1-2 g
  5. 5
    Otherdry weight of the resin
  6. 6
    Concentration, the phospholipid and doxorubicin concentration

Procedure

1 ml of a 10 mg/ml solution of doxorubicin HCl dissolved in saline-desferal was added to I ml of the liposome dispersion after the liposomes were gel filtrated on a Sephadex G-50 column. The mixture was incubated at room temperature for approximately 24 hours. The incubation was shorter for certain types of kinetic experiments. At the end of incubation period, the mixture was passed through a Dowex 50 WX-4 column to adsorb the free drug. The resin is able to adsorb as much as 1 mg of free doxorubicin in a 15 min time while the sequestered liposome incorporated remains with the liposomes. A column containing 1-2 g dry weight of the resin was sufficient to adsorb all unincorporated drug. To determine the ratio of incorporated drug to liposomal lipid., the phospholipid and doxorubicin concentration were determined as described previously.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05316771uspto-grants-1994_05