What are liposomes?

Lipidic nanoparticles/colloidal vesicles

Artificially prepared, closed phospholipid bilayer, fluidic systems
First described by Alex Bangham in 1961
Greek: =fat, =body

Backgroun
d

Phospholipid
Phospholipids
bilayer can include phosphatidylcholine,

Liposome/vesicle
type

Lipid
bilaye
r

Size

small unilamellar
(SUV)

single

20nm100nm

large unilamellar
(LUV)

single

100nm400nm

giant unilamellar
(GUV)

single

1m and
greater

large multilamellar
(MLV)

multipl
e

200nm3m

dipalmitoylphosphatidylcholine or
phosphatidylethanolamine.
Cholesterol maintains fluidity and structural
Cholesterol:
integrity.

Other applications

multivesicular (MVV)
multipl
Liposome
Drug
e
product
carried

200nmApplication
3m

Caelyx/
Myocet/Doxil

Doxorubicin

Breast &
ovarian
cancers,
Kaposis
sarcoma

AmBisome

Amphotericin
B

Diprivan

Propofol

The applications of liposomes can be divided into

therapeutic and diagnostic. Their applications in
different fields is due to their versatility and
compatibility.
Bioengineering applications of liposomes is the
As good and important as liposomal drugs
focus
are, there are some disadvantages of
considered here and some
advantages
utilising liposomal drugs. These include:
include:
Sterilisation of the liposome during
Sustained release drug delivery
production process
Site avoidance delivery
Stability of the drug
Site specific targeting
Short half life of the drug in the blood
Passive and active targeting
stream and at the site of action
Improved solubility of lipophilic and
High production cost
amphiphilic
drugs
Improved transfer of hydrophilic charged
molecules

Applications/
Advantages &
Disadvantages

Anaesthetic

tu
e
C
ab

Mansoubi-H

osseini, Mic
hael Oladim
a
eji, Emily Kn
n
d
N
atalie Kaof
School of Biosciences, University
ight
raKent,
minaCanterbury
s

Vaccines; antiinflammatory drugs;

gene medicines;
nucleic acid polymers;
cosmetic ingredients;
nutritional & dietary
supplements; imaging;
biodetoxification

Fungal
infections
leishmaniasis

Engineering
liposomes

Liposomal Drug
Delivery

Masoumeh

TAT

xim

One of the most recent

liposomal drugs
(FDA approved, August
Estrasorb
Estrogen
Menopausal
2012) is Marqibo carrying Vincristine
acute lymphoblastic
therapy

Flu
cil

som
o
Lip
e

PEGylatio
n

a
r
u
o
or

mAbs

leukaemia at relapse.

methanol). Evaporate to form a thin lipid film. Hydrate by adding aqueous

buffer (which can contain drugs) which causes the lipids to swell and peel off
to form multilamellar vesicles (MLVs). These can then be sonicated by high
frequency sound waves which causes breakdown of MLVs to small
unilamellar vesicles (SUVs).

Our designed drug is a small unilamellar

Our Liposomal
liposome containing the cytotoxic drug
fluorouracil which is an anti-metabolite used in
Drug
On the liposome surface there is:
the treatment of colorectal cancer.
PEGylation masking the liposome from the immune system
Cetuximab (a mAb) for improved cell targeting of metastatic
colorectal tumour cells.
TAT for improved cell penetration. TAT is protected from degradation by
further PEGylation which is pH sensitive. The pH in tumour tissue is
approximately 5-6. At this reduced pH, the PEG sheds to reveal TAT.

Referen
ces

T
TA

Preparatio
PEG
Dissolve
n phospholipids in solution of organic solvents (e.g. chloroform and

PEG
+
mAb

pe TAT
pt
ide

At the target
site, the
liposome loses
its pH sensitive
shell and the
cell-penetrating
action of TAT
occurs,
resulting in
intracellular
drug delivery.

Liposomal drug
loading

Encapsulation of hydrophobic
drugs:
During the preparation in the
subsequent hydration phase, drugs
would trap in the hydrophobic bilayer
area.
Encapsulation of hydrophilic
drugs:
Transmembrane pH gradients
Proton-generating dissociable
salts

The stability of liposomes can be promoted in

several ways:
Increasing saturation by using cholesterol
Applying lower internal pH environments in
the liposome
PEGylation
coupling of
Increasinginvolves
the drugcovalent
to lipid ratio
polyethylene glycol to the phospholipid, which
results in a significant increase in circulation halfby preventing opsonization.
life
Monoclonal antibodies (mAbs) lead liposomes to the
specific target site. Attaching mAbs at the end of
PEG is preferable, otherwise PEGylation may
obstruct them.
Cell-penetrating
tag further improves intra
cellular drug delivery of nanoparticles (e.g TAT
peptide).

Summary
Liposomes are artificially prepared nanoparticles which
have a multitude of biotechnological applications. The
ability to add surface decorations to alter the properties
of liposomes makes them a valuable tool in drug design.
The addition of PEGylation, mAbs and TAT protein
enabled us to design a novel cancer therapy which could
potentially be used in the treatment of colorectal and
other cancers.

Allen TM, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2012;64, Supplement(0):206-212.
Koren E, Apte A, Jani A, Torchilin VP. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Controlled Release. 2012;160(2):264-273
Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, HanifehpourY, Nejati-Koshki K. Liposome: classification, preparation, and applications. Nanoscale Research Letters. 2013;8(1):102.