Lipoproteins as

Pharmaceutical Carriers

Lipoproteins as Pharmaceutical
Carriers
Lipoproteins are such structures which function as natural
biological carriers and transport various types of lipids in
blood circulation
Lipoproteins - efficient carriers for anticancer drugs, gene or
other type of compounds.
Endogenous components(Lipoproteins) do not trigger
immunological response.
Relatively long half-life in the circulation.
Small particle size - allowing the diffusion from vascular to
extravascular compartments.
Lipoproteins can potentially serve as the carriers for targeted
drug delivery through specific cellular receptors. E.g. low
density lipoprotein (LDL)-drug complexes may target cancer
cells.
Compartment for carrying hydrophobic drugs

Classes of lipoproteins
Chylomicron
Very low-density lipoprotein (VLDL)
Low-density lipoprotein (LDL)
Intermediate-density lipoprotein (IDL)
High-density lipoprotein (HDL)

Structure of Lipoproteins

Physicochemical properties of
lipoproteins
Lipoprotei
n

Transport
Route

Chylomicron Intestines to
Liver

Size(nm)

Protein (%) Total lipids

(%)

75-1200

1.5-2.5

97-99

VLDL

Liver to
tissues

30-80

5-10

90-95

IDL

Liver to
tissues

25-35

15-20

80-85

LDL

Liver to
tissues

18-25

20-25

75-80

HDL

Tissues to
liver

5-12

40 55

45 60

Chylomicron as Pharmaceutical
Carrier
Chylomicrons - natural carrier for hydrophobic
drugs to transport through lymphatic system.
Chylomicrons - much larger size than other
lipoproteins, and thus can carry more drug
molecules from the absorption site.
With the presence of food - predominant
lipoprotein produced by the small intestine to
carry dietary lipids efficiently because of its large
size.
Chylomicrons in gene delivery Reconstituted chylomicron which incorporated
a hydrophobic DNA complex and used it as an in
vivo gene transfer vector.

Chylomicron as Pharmaceutical
Carrier

Targeted therapeutic approach to hepatitis B,

anti-viral iododeocyuridine was incorporated into
recombinant chylomicrons
Drug molecules being selectively targeted to the
liver parenchymal cells.
Suggested that chylomicron can serve as a
special carrier for liver cell targeting.
Due to the targetability, this approach could be
further developed as an effective therapy for
hepatitis B patients.

VLDL as Pharmaceutical Carrier

Catabolism route of VLDL suggests the possibility of
using VLDL as a drug carrier for targeted delivery.
ApoE is a protein ligand present on the surface of
VLDL - receptor of apoE is overexpressed on some
types of cancer cells potential for antineoplastic
drug carrier.
Nanoemulsion formulation was used to encapsulated
quantum dots (QD) as a new bioimaging carrier.
Quantum
dots
(QDs)
are
semiconductor
nanocrystals that are emerging as unique
fluorescence probes in biomedicine.

VLDL as Pharmaceutical Carrier

To encapsulate QDs in phospholipid nanoemulsion
and to examine the physical stability, size
distribution and their interactions with cancer
cells.
CdSe QDs can be efficiently encapsulated in the
phospholipid nanoemulsion.
QD-encapsulated phospholipid nanoemulsion are
stable and interact well with cultured cells to
deliver the QDs inside the cells for fluorescence
imaging.
It has been demonstrated that cytotoxic drugs
such as 5-fluorouracil (5-FU), 5-iododeoxyuridine
(IudR), doxorubicin (Dox), and vindesine can be
effectively incorporated into VLDL, and the

LDL as Pharmaceutical Carrier

LDL receptor pathway and targeted drug

delivery.

LDL as Pharmaceutical Carrier

LDL as anticancer drug carriers
LDL has been studied as a target carrier for Doxorubicin in nude
mice, bearing human hepatoma HepG2 cells.
Both in vitro and in vivo studies indicated that when Dox was
incorporated into LDL, the multidrug resistance could be
circumvented and the cardiotoxicity could be reduced as well.
LDL as carriers for other types of bioactive compounds
Site-specific delivery of drugs to atherosclerotic lesions.
Dexamethasone palmitate (DP), a steroidal anti-inflammatory drug,
was incorporated in LDL, an inhibitory effect of this complex on
foam cell formations was demonstrated.
Study indicated that LDL could potentially carry DP to
atherosclerotic lesions.
LDL for gene delivery
Kim's group developed a terplex system which comprises LDL,
lipidized poly (Llysine) and plasmid DNA.
Complex had a diameter of about 100 nm.
Studies showed high efficiency to deliver plasmid DNA to smooth
muscle cells and fibroblast cells.

HDL as Pharmaceutical Carriers

Taxol(Anti-cancer Drug), was incorporated into
HDL, stable complexes were formed and they
were examined for cancer-cell targeting.
Reconstituted HDL was explored as a drug carrier
system for a lipophilic prodrug, IDU-OI2.
Studies indicated that the lipophilic prodrug could
be efficiently incorporated into reconstituted HDL
particles.
This approach may also be useful to encapsulate
other lipophilic derivatives of water-soluble drugs.

Cholesterol-rich Emulsions (LDE)

as Pharmaceutical Carriers
Comparing with native LDL, LDE is removed from
the blood circulation more rapidly.
LDE - potential carrier for anticancer drugs.
LDE binds to low-density lipoprotein receptors
which are upregulated in cancer cells, leading to a
higher concentration in neoplastic tissues.
Rodrigues et ah investigated the formulation of
LDE containing antineoplastic compound paclitaxel.
Experiments revealed a 75% incorporation
efficiency and the stable complex of the drug
molecules incorporated in LDE emulsion.
LD50 was ten-fold greater than that of a
commercial formulation of paclitaxel

Conclusion
Lipoproteins are natural nanostructures in
biological systems
Unique physicochemical properties - utilized as
pharmaceutical carriers for drug compounds and
other bioactive substances.
LDE and artificial lipoproteins, can also be
constructed to mimic the structure of natural
lipoproteins.
Nanostructures more efficient in encapsulating
drug and other bioactive molecules, and
More effective for specialize drug delivery.