Liposomal drug delivery system(LDDS)
Course Instructor
Dr. Sohel Rana
Professor
Dept. of Pharmacy, Jahangirnagar Universit...
LIPOSOME
liposome derives from two Greek words:lipo("fat")
and soma ("body"); it is so named because its
composition is pr...
List of Some clinically approved liposomal drugs
Name Trade name Company Indication
Liposomal amphotericin
B
Abelcet Enzon...
Application of Liposomes
• Intracellular drug delivery
• Site-avoidance delivery
• Site-specific targeting
• Enzyme replac...
Advantages of LDDS
Advantage
 Suitable for delivery of hydrophobic, hydrophilic and amphipatic drugs and
agents
 Chemica...
Disadvantage of LDDS
Disadvantage
 their rapid clearance from circulation due to uptake,
 by the reticuloendothelial sys...
Classification
based on the ability of liposomes to
interact with cells
• non-interactive sterically stabilized
(long-circ...
Mechanism of liposomal drug delivery
A liposome encapsulates a region of aqueous solution inside
a hydrophobic membrane; d...
Liposome Preparation
Lipid in organic solvent solution
Evaporation
Extrusion (or sonication)
Liposomes and unencapsulated ...
Methods of liposome preparation
Solvent dispersion
methods
Ethanol injection
Ether injection
Double emulsion
vesicles
...
Why Use Liposomes in Drug Delivery?
Drug Targeting at specific
-Cell
-Tissue
- Receptor
- pH resone
Inactive: Unmodified l...
Pharmokinetics - efficacy and toxicity
-Changes the absorbance and biodistribution
- Deliver drug in desired form
- Delive...
Stability
• One of the major problems limiting the widespread
use of liposomes is stability--both physical and
chemical.
•...
All for your kind
attention
Liposomal drug delivery system
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Transcript of "Liposomal drug delivery system"

  1. 1. Liposomal drug delivery system(LDDS) Course Instructor Dr. Sohel Rana Professor Dept. of Pharmacy, Jahangirnagar University Submission Date: 28.08.2013 Submitted By: Nazmul Islam Ms in Pharm Tech,Dept of Pharmacy,UAP Contact:(uap_nazmul2yahoo.com)
  2. 2. LIPOSOME liposome derives from two Greek words:lipo("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid. Liposomes are microparticulate lipoidal vesicles which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents, composed of relatively biocompatible and biodegradable material, and they consist of an aqueous volume entrapped by one or more bilayers of natural and/or synthetic lipids.
  3. 3. List of Some clinically approved liposomal drugs Name Trade name Company Indication Liposomal amphotericin B Abelcet Enzon Fungal infections Liposomal amphotericin B Ambisome Gilead Sciences Fungal and protozoal infections Liposomal cytarabine Depocyt Pacira (formerly SkyePharma) Malignant lymphomatous meningitis Liposomal daunorubicin DaunoXome Gilead Sciences HIV-related Kaposi’s sarcoma Liposomal doxorubicin Myocet Zeneus Combination therapy with cyclophosphamide in metastatic breast cancer Liposomal IRIV vaccine Epaxal Berna Biotech Hepatitis A Liposomal IRIV vaccine Inflexal V Berna Biotech Influenza Liposomal morphine DepoDur SkyePharma, Endo Postsurgical analgesia Liposomal verteporfin Visudyne Novartis Age-related macular degeneration, pathologic myopia, ocular histoplasmosis Liposome-PEG doxorubicin Doxil/Caelyx Ortho Biotech, Schering- Plough HIV-related Kaposi’s sarcoma, metastatic breast cancer, metastatic ovarian cancer Micellular estradiol Estrasorb Novavax Menopausal therapy
  4. 4. Application of Liposomes • Intracellular drug delivery • Site-avoidance delivery • Site-specific targeting • Enzyme replacement • Study of membranes • Oral Drug Delivery • Gene Therapeutics • Formulation aid • Cosmetics • Chelation therapy for treatment of heavy metal poisoning. • Liposomes as Protein Carriers in Immunology • Sustained or Controlled Delivery • Diagnostic imaging of tumors
  5. 5. Advantages of LDDS Advantage  Suitable for delivery of hydrophobic, hydrophilic and amphipatic drugs and agents  Chemically and physically well characterized entities  Biocompatible  Use as carrier for suitable for controlled release drug delivery.  Suitable to give localized action in particular tissues.  Suitable to administer via various routes  Increased efficacy and therapeutic index.  Reduction on toxicity of the encapsulation agent.  Improved pharmacokinetic properties.  Can be made into Varity of drug.  Minimum antigenicity.
  6. 6. Disadvantage of LDDS Disadvantage  their rapid clearance from circulation due to uptake,  by the reticuloendothelial system(RES), primarily in the liver  Leakage of encaptulation drug delivery during storage.  Batch to batch variation.  Once administered, can’t removed.  Difficult in large scale manufacture and sterilization.  Physical /chemical stabillity  Very high production cost  Possibility of dumping due to faulty administration.
  7. 7. Classification based on the ability of liposomes to interact with cells • non-interactive sterically stabilized (long-circulating) liposomes (LCL) and; • highly interactive cationic liposomes. Based on size and number of bilayers • multilamellar vesicles (MLV); • large unilamellar vesicles (LUV); • small unilamellar vesicles (SUV). Based on composition and mechanism of intracellular delivery • conventional liposomes (CL); • pH-sensitive liposomes; • cationic liposomes; • immunoliposomes; • long-circulating liposomes (LCL).
  8. 8. Mechanism of liposomal drug delivery A liposome encapsulates a region of aqueous solution inside a hydrophobic membrane; dissolved hydrophilic solutes cannot readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents.
  9. 9. Liposome Preparation Lipid in organic solvent solution Evaporation Extrusion (or sonication) Liposomes and unencapsulated SRB Lipid film Freeze/thaw cycles Gel filtration Purified liposomes Hydrate with sulforhodamine B (SRB) solution
  10. 10. Methods of liposome preparation Solvent dispersion methods Ethanol injection Ether injection Double emulsion vesicles Stable plurilamellar Vesicles Reverse phase evaporation vesicles Detergent removal methods Passive loading techniques Detergent(Cholate, Alkyl glycoside, Triton X-100) removal from mixed micelles by Dialysis Column chromatography Dilution Reconstituted sendai virus enveloped vesicles Active loading techniques Lipid film hydration by hand shaking non-hand shaking and freeze drying Micro emulsification Sonication French pressure cell Membrane extrusion Dried reconstituted vesicles Freeze thawed liposomes Mechanical dispersion methods 10
  11. 11. Why Use Liposomes in Drug Delivery? Drug Targeting at specific -Cell -Tissue - Receptor - pH resone Inactive: Unmodified liposomes gather in specific tissue reticuloendothelial system Active: alter liposome surface with ligand (antibodies, enzymes, protein A, sugars) Protection - Decrease harmful side effects (Change where drug accumulates in the body)
  12. 12. Pharmokinetics - efficacy and toxicity -Changes the absorbance and biodistribution - Deliver drug in desired form - Deliver drug in desired form Protection - Decrease harmful side effects (Change where drug accumulates in the body) Release - Affect the time in which the drug is released - Prolong time -increase duration of action and decrease administration Dependent on drug and liposome properties Liposome composition, pH and osmotic gradient, and environment.
  13. 13. Stability • One of the major problems limiting the widespread use of liposomes is stability--both physical and chemical. • Depending on their composition, the final liposome formulations may have short shelf-lives partly due to chemical and physicalinstability. (1)Chemical instability may be caused by hydrolysis of ester bond and/or oxidation of unsaturated acyl chains of lipids. (2)Physical instability may be caused by drug leakage from the vesicles and/or aggregation or fusion of vesicles to form larger particles. Both of these processes (drug leakage and change in liposome size) influence the in vivo performance of the drug formulation, and therefore may affect the therapeutic index of the drug.
  14. 14. All for your kind attention

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