Camposomes™
Camptothecin
is an antitumor alkaloid that is isolated from the bark and
stem wood of Camptotheca acuminata, a small tree native to
China. This compound displays unprecedented antitumor activities
against leukemia, human colon cancer and a variety of solid
tumor systems. In particular, it was discovered that camptothecin
traps the cleavable complex between topoisomerase I and DNA.
Camptothecin is a unique topoisomerase I inhibitor which,
while very effective, is not yet completely understood. In
addition to its potent anticancer activity, camptothecin inhibits
the replication of HIV and other viruses.
The
full therapeutic activity of camptothecin has been limited
by poor water solubility and aqueous instability of the lactone
ring moiety. Ring opening will cause loss of biological activity
of this compound. Preferential binding of the biologically
inactive carboxylate form with human serum albumin further
hinders drug effectiveness. Administration of the soluble
sodium salt of camptothecin has proved to be ineffective and
has delayed the development of this potent anticancer compound.
As a result of this, camptothecin analogs that exhibit a superior
solubility profile while retaining antitumor activity are
being developed. These goals are frequently at odds, as increased
hydrophilicity engenders greater exposure to the deactivating
aqueous environment. Several promising clinical candidates,
such as topotecan, CPT-11, and 9-aminocamptothecin, have emerged;
topotecan and CPT-11 have been approved by the FDA for colorectal
and other cancers.
Water
soluble camptothecin analogs have yet to prove as effective
as the native compound and some of its hydrophobic analogs.
Liposomes are a useful drug delivery system for solubilizing
camptothecin, while retaining both its lactone ring and antitumor
activity. Hydrophobic compounds are trapped inside the lipid
bilayers, masking the drug’s toxic nature and permitting
a biocompatible formulation to be administered.
Aphios
has utilized its patented SuperFluids™ CFN technology
(US Patent Nos. 5,554,382 and 5,776,486) to form nanosomes
(small, uniform liposomes) of camptothecin called Camposomes™.
Liposomes are microscopic vesicles of phospholipid bilayers
comprised of single or multiple lipid bilayers. Most liposomes
are non-toxic, non-antigenic and biodegradable in character
since they have the molecular characteristics of mammalian
cell membranes.
The
US National Cancer Institute conducted in vivo testing of
Camposomes™, which were formulated using Aphios’
SuperFluids™ CFN critical fluid injection technique.
Camposomes™ had a size distribution centered at 100
nm (S.D. 35 nm). The camptothecin concentration of the liposomal
solution produced was 1.1 mg/mL by HPLC assay. Four groups
of 10 mice were implanted with lymphoma xenografts and given
intravenous treatment. For the highest dose (11 mg/Kg) tested,
3 were found to be tumor-free (cured) after 69 days with no
drug-related deaths.
Camposomes™
will improve the efficacy, reduce the toxicity, and improve
the solubility and stability of this unique topoisomerase
I inhibitor and anticancer drug. We are seeking strategic
corporate partners to continue the development of Camposomes™.
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