DepoFoam
TM
of Sky Pharma and is a treatment for lymphomatous
meningitis, a compli cation of late-stage lymphoma. Lymphomatous meningitis
can be controlled with cytarabine, but the drug’s short half-life (plasma
elimination half-life of = 720 min) requires a spinal injection every other day,
distressing for the patient and incurring high nursing costs. DepoCyt cuts the
injection frequency to every second week, allowing treatment on an outpatient.
DepoCyt was introduced in the United States in 1999. DepoCyt consist of
spherical particles composed of numerous nonconcentric internal aqueous
chambers containing the encapsulated drug. Each chamber is separated from
adjacent chambers by bilayer lipid membranes composed of synthetic analogs
of naturally occurring lipids (dioleoyl phosphatidylcholine, dipalmitoyl
phosphatidylglycerol, cholesterol, triolein) [104]. Studies have shown that,
compared with unencapsulated cytarabine, intrathecal administration of
DepoCyt provides a significant pharmacokinetic advantage that maximize s
the therape utic potential of cell cycle S-phase-specific cytotoxicity agents. In
addition, the prolonged CSF t
1/2
of cytarabine provided by this novel
formulation may permit less frequent dosing, which is particularly convenient
for intrathecal administration [104, 105].
16.3.1.7 Liposome Vaccine
Known vaccines typically utilize either purified antigen or attenuated pathogen
as the immunogen. However, attenuated vaccines can actually cause the
infection against which a person is being immunized. On the co ntrary, purified
antigens may not induce a long term immune response and sometimes induce
no response at all. In contrast to the short-term immune response obtained by
direct immunization with certain antigens, presentation of the antigen in the
presence of liposomes can induce a long term response that is essential for any
effective vaccine. Various studies showed that liposomes might also be formed,
at least in part, from cell membranes of malignant cells that contain potential
antigens. Due to the presence of membrane-associated antigens, these
membrane-derived preparations may be used as malignancy-specific vaccines.
Indeed, some types of membrane-derived preparations have been used as
tumor-specific antigens to treat melanomas and murine SL2 lymphosarcoma
[106–108].
In a study, a synthetic human MUC1 peptides (25 amino acid sequence)
known as BLP 25 was studied for their therapeutic application as cancer
vaccines. It was shown to render immunogenic by incorporation in liposomes,
the effects of physical association of the peptide with liposomes on immune
responses wer e investigated. Lipid conjugated and nonconjugated MUC1
peptides were incorporated in liposomes with a composition of distearoylpho-
sphatidylcholine, cholesterol, dimyristoylphosp hatidylglycerol (3:1:0.25, molar
ratio) containing monophosphoryl lipid A (1% w/w of the total lipids).
C57BL/6 mice were immunized with lipopeptide alone, peptide mixed with
peptide-free liposomes, and peptide associated with liposomes in entrapped or
NANOSTRUCTURES FOR CANCER THERAPY 425