Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a comparison of whole monoclonal antibody, Fab' fragments and single chain Fv.

As part of an ongoing effort to develop a clinically acceptable doxorubicin formulation, targeted against B-cell malignancies, this study compared long-circulating (Stealth) immunoliposomes (SIL) that were targeted against the B-cell antigen CD19, via a whole HD37 monoclonal antibody (HD37 mAb), versus its Fab' fragment (HD37 Fab') or an HD37-c-myc-Cys-His5 single chain Fv fragment (scFv, HD37-CCH) directed against the same epitope. Compared to untargeted liposomes (SL), SIL showed increased binding in vitro to CD19-expressing Raji cells and, when loaded with doxorubicin (SIL-DXR), increased cytotoxicity against Raji (CD19(+)), but not Molt4 (CD19(-)) cells. Pharmacokinetics and biodistribution studies using dual-labeled liposomes (lipid and drug) in naive and Raji-bearing mice showed that SIL-DXR targeted via HD37 Fab' exhibited the same long circulation half-life as SL-DXR.

Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer.

Nanoscale drug delivery systems (DDS) are used to circumvent some of the non-ideal properties of conventional anticancer chemotherapy drugs. Manipulation of the physical properties of DDS provides improved control over the pharmacokinetics (PK) and pharmacodynamics (PD) of the encapsulated drugs relative to free drugs. Liposomes are the archetypical nanoscale DDS and the first of these received clinical approval in 1990.