Introduction to liposomes and its types.

1. Liposomes

2. What’s the meaning of Liposomes???
*Liposomes are microscopic phospholipid bubbles with a
bilayered membrane structure.
*Many new developments have been seen in the area of
liposomal drugs, from clinically approved products to new
experimental applications, with gene delivery and cancer
therapy still being the principal areas of interest.

3. Some History…
50 years ago Alec Bangham noticed that phospholipids in aqueous
systems can form closed bilayered structure.
•Since then they came from being an exotic object in research to common
drug carrier with many clinical applications.
Example: Doxorubicin in polyethylene glycol (PEG) liposomes for
the treatment of solid tumors in patients with breast-carcinoma
metastases which improved survival.

4. Types of Liposomal vesicles:

5. Attractive Biological Properties:

6. Goals of Liposomes Surface Modification:

7. Liposomes in Drug Delivery: Evolution
• One of drawbacks of use of liposomes is fast elimination
from blood & capture of liposomal preparations by cells
of RES mainly in liver.
• To reduce this problem:
1) Immunoliposomes: To increase liposomal drug
accumulation in desired tissues. Use of targeted
liposomes with surface attached ligands able to recognize
& bind to desired cells. IgG are most widely used
targeting moieties for liposomes.
2) Long circulating liposomes: Include coating liposome
surface with inert, biocompatible polymers as PEG ,
which slow down liposome recognition by opsonins and
therefore clearance of liposomes.

8. Liposomes in Drug Delivery: Evolution
• Although, PEG remains the gold standard for the steric
protection of liposomes, attempts continue to identify other
polymers that could be used to prepare long-circulating
liposomes.
• Earlier studies with various water-soluble flexible polymers
have been summarized elsewhere.
• More recent papers describe long-circulating liposomes
that were prepared using poly [N-(2-hydroxypropyl)
methacrylamide)] ,poly-N-vinylpyrrolidone, L-amino-acid-
based biodegradable polymer lipid conjugates and polyvinyl
alcohol.

9. Liposomes in Drug Delivery: Evolution
3) Long-circulating Immunoliposomes:
• Involved the combination of the properties of long-
circulating liposomes and immunoliposomes in one
preparation.
• Performed by simple co-immobilization of an antibody and
PEG on the surface of the liposome, although the protective
polymer can create steric hindrances for target recognition
with the targeting moiety.
• Solution : To achieve better selectivity of PEG-coated
liposomes, it is advantageous to attach the targeting ligand
via a PEG spacer arm, so that the ligand is extended outside
of the dense PEG brush, which reduces steric hindrance.

10. Liposomes Surface Modification Chemistry
• The preparation of modified Liposomes with controlled properties requires the
chemical conjugation of proteins, peptides , polymers and other molecules to the
liposome surface.
• The conjugation methodology is based on 3 main Rxs :
1- reaction bet. Activated carboxyl gps and amino gps , which yields an amide bond.
2- reaction bet. pyridyldithiols and thiols, which yields disulfide bonds.
3- reaction bet. Maleimide derivatives and thiols, which yields thioether bonds.
• Many lipid derivatives used in these techniques are comercially available.
• Other approaches exist ,such as those that yield the carbamate bond via the
reaction of p-nitrophenylcarbonyl and amino gp.

11. New Ligands for Targeting Liposomes
• Examples for Antibody-mediated liposome targeting :
1) using anti-HER2 liposomes to target HER2-overexpressing
tumors.
2) NUCLEOSOME-specific antibodies have improved Doxil
targeting to tumour cells.
• Folate-mediated liposome targeting: A popular approach,
because folate receptors (FR) are frequently overexpressed
in a range of tumour cells.
• Possibility of delivering macromolecules and then liposomes
into living cells using FR endocytosis, which could bypass
multidrug resistance.

12. New Ligands for Targeting Liposomes
Transferrin-mediated liposomal targeting: TF-receptors over expressed
on surface of many tumor cells so coupling of TF on pegylated
liposome was successfully used for brain targeting.
Vasoactive intestinal peptide (VIP): Has been used to target PEG
liposomes with radionuclides to VIP receptors on surface of tumor
cell and resulted in enhanced breast cancer inhibition in rats.
Epidermal growth factor receptor (EGFR): EGFR-targeted liposomes
delivered to tumor cells that over express EGFR.
Galactosylated liposome: Research also continues on the use of
galactosylated liposomes to target drug to Liver for the treatmentof
liver tumors and metastases.
Cisplatin-loaded liposomes: Bind to chondroitin sulphate which is over
expressed in many tumor cells have been used for suppression of
tumor growth.

13. PH Sensitive Liposomes
• Focus on development of new lipid composition that confer PH
sensitivity to liposomes by using PH sensitive polymers.
• Combining PH sensitive liposomes with longevity and ligand
mediate targeting.
• Pegylated PH sensitive liposomes have long duration.
• Antisense oligonucleotides can be delivered into cells by anionic
pH-sensitive phosphatidyl ethanolamine .
• containing liposomes that are stable in the blood but which,
however undergo phase transition at acidic endosomal pH.
• Ex. oleyl alcohol and a mono-stearoyl derivative of morpholine.
• liposome pH-sensitivity and specificity of ligand targeting (folate
and targeted liposomes).

14. PH Sensitive Liposomes

15. References…
This Presentation is based on:
RECENT ADVANCES WITH LIPOSOMES AS
PHARMACEUTICAL CARRIERS
By~ Vladimir P. Torchilin