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Drug Delivery with liposome. Pei Hsuan Wu Yi Chieh Chung. What is a liposome?. Spherical vesicles with a phospholipid bilayer. 50-100 nm. Hydrophilic. Figure 1. liposome. Figure 2. Phospholipid bilayer. Hydrophobic.

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drug delivery with liposome

Drug Deliverywith liposome

Pei Hsuan WuYi Chieh Chung

what is a liposome
What is a liposome?
  • Spherical vesicles with a phospholipid bilayer

50-100 nm

Hydrophilic

Figure 1.

liposome

Figure 2.

Phospholipid bilayer

Hydrophobic

Liposomes were first observed by British haematologist Alec D Banghamin 1961 (published 1964), at the Babraham Institute, in Cambridge[1]

the role of nano technology
The role of nano-technology

Because the phospholipid bilayer is thin and fragile, it need good nano-technology to control and Manufacture.

Figure 3. TEM images of liposome [2]

uses of liposomes
Uses of Liposomes
  • Chelation therapy for treatment of heavy metal poisoning
  • Nutritional supplements
  • Diagnostic imaging of tumors
  • Transgenesis
  • Drug Delivery
why use liposomes in drug delivery
Why Use Liposomes in Drug Delivery?
  • The absorbance and biodistribution
  • Protects drug
  • Decrease harmful effects
  • Deliver drug in desired form
  • Multidrug resistance

Due to the hydrophilic

and hydrophobic of the phospholipid layer.

medicine

Phospholipid layer

why use liposomes in drug delivery1
Why Use Liposomes in Drug Delivery?

2.Inactive

Unmodified liposomes gather in specific tissue.

medicine

Liposome

1.Drug Targeting

3.Active

alter liposome surface with ligand

4.Physical

temperature or pH sensitive liposomes

drug targeting
Drug Targeting
  • Pharmokinetics - efficacy and toxicity
  • Decrease harmful side effects

Examples:leishmaniasis, amphotericin B……

  • Change where drug accumulates in the body

Examples:

Cancer Therapy

Figure 4. Cancer cell[5]

stay inactive
Stay inactive
  • Deliver drug in desired form
  • Protection medicine from Immune System

Pretend to be Erythrocyte

Example:

PEG Liposome Coating

Sialic acid Coating

Figure 5. Erythrocyte

[1]

react with active
React with active
  • How to release the medicineMacrophage, cell membrane..
  • When to release the medicine

Affect the time in which the drug is released.

Prolong time -increase duration of action anddecrease administration.

Figure 6. Macrophage[1]

modes of liposome cell interaction
Modes of Liposome/Cell Interaction

Endocytosis

Adsorption

Lipid transfer

Fusion

pld doxil caelyx
PLD (Doxil, Caelyx)
  • PEG Liposome Coating: hydrophilicity; opsonization
  • Drug loading gradient: encapsulation efficiency, drug retention

PEG

DRUG

Doxorubicin

Evades reticulo-endothelial

system – “Stealth”Effect

Prolonged circulation

80-90 nm

Drug stays in liposome until

it reaches “permeable” tissue

Passive Tumor Targeting

Lipid Bilayer

marked drug deposition in subcutaneous tumor implants 48 hrafter i v pld
Marked Drug Deposition in Subcutaneous Tumor Implants 48 hrAfteri.v. PLD*

Skin = 0.5 µg/g

Tumor

86 µg/g

Halo

40 µg/g

*20 mg/kg

Analysis of Drug Levels

plasma levels prolonged half life pld vs doxorubicin single dose 50 mg m 2

2

5

.

0

1

.

0

0

.2

0

.1

Plasma Levels: prolonged half-lifePLD vs. doxorubicin (Single Dose, 50 mg/m2)

10.0

PLD (T½=50-80 hours)

2.5

Doxorubicin (µg/mL)

Doxorubicin

0

4

8

12

16

20

24

Hours After Infusion

Gabizon et al., Cancer Res. 1994

slide14
Stealth liposome localization in human tumors Gamma Scintigraphy 24 and 48 Hours after Injection of Radiolabeled Stealth Liposomes

(Posterior view)

Lung Tumor

Spleen

Liver

Bone Marrow

Harrington et al.,

Clin. Cancer Res. 2001

reference
Reference
  • [1] Wikipediahttp://en.wikipedia.org/
  • [2] “Carbon nanotube–liposome supramolecularnanotrains for intelligent molecular-transport systems Eijiro” ,Miyako1, Kenji Kono2, Eiji Yuba2, Chie Hosokawa1, Hidenori Nagai1 & Y oshihisaHagihara1.
  • [3]"Liposomes", D. Lasic, American Scientist, Vol. 80, January-February 1992.
  • [4] “Lipid-based materials” Chi-Wei Lan , Biorefinery & Bioprocess Engineering Laboratory,Departmentof Chemical Engineering and Materials Science, Yuan Ze University
  • [5] Cancer Research UK http://www.cancerresearchuk.org