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Drug Delivery with liposome

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

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  1. Drug Deliverywith liposome Pei Hsuan WuYi Chieh Chung

  2. 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]

  3. 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]

  4. Uses of Liposomes • Chelation therapy for treatment of heavy metal poisoning • Nutritional supplements • Diagnostic imaging of tumors • Transgenesis • Drug Delivery

  5. 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

  6. 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

  7. 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]

  8. 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]

  9. 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]

  10. Modes of Liposome/Cell Interaction Endocytosis Adsorption Lipid transfer Fusion

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

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