Liposomes_BSPS

Liposome

  • Lipo = fat

  • soma= body

Phospholipids

  • When phospholipids are dispersed in water they spontaneously form closed structures with Internal Aqueous Compartments

  • separated by aqueous compartments

  • micro and non-particle dug carriers

Advantages of Liposomes

  • Suitable for delivery of Hydrophobic, Hydrophilic, and Amphipathic drugs and agents

  • Chemically and physically well characterized

  • Biocompatible, biodegradable, and eliminated

  • sustained controlled release

    • relate drug at a constant rate in specific amounts over a specified period of time

  • administer it in various route

Structure of Liposome

  • Phospholipid tail (water fearing, hydrophobic)

  • Unsaturated is bent

  • Saturated fatty tail is straight

  • Hydrophilic head containing Choline, Phosphate, and Glycerol

Materials used in Liposome Preparation

  • Glycerol containing phospholipids

    • most abundant are phosphotidyl choline (lecithin) and phosphotidylethanolamine (cephaline)

  • Fatty acids are important constituent of glycerol phosphatides

Sphingolipids

  • contain sphingosine ( attached to a phosphate group), structural backbone

  • Most abundant form is an Sphingomylein

Glycosphingolipids

  • found in grey matter of brain tissue

  • included in liposomes formulation to provide a layer od surfaced charged groups

Sterols

  • Cholesterol and included in liposomal membrane

  • Cholesterol can be added to bilayer mixture forthe following purposes

    • fluidity buffer

    • intercalator

    • decreases permeability of membrane to water soluble molecules

Synthetic Phospholipids

  • Saturated

    • Include DDPC, DDPE, DPPS, DSPC

  • Unsaturated

    • DOPC. DOPG

Classification of Liposomes

  • Size of liposome

    • Small unilamellar vehicles (150 nm), Medium, large, Giant, Oligomalaellar, multi, Multivesicular

  • Method of preparation

  • composition an in vivo application

Methods for Controlling Liposome Size

  • Membrane pore Extrusion

    • liposofats or lipex

  • Homogenization

    • emulsiflex

  • Sonication

  • Fractionation

    • centrifugation

    • size exclusion chromatography

Classification based on methods and Preparation

Dry “thin” Film

  • Liposomes are formed when think lipid fils are hydrated

  • The hydrated lipid sheets detach during agitation and form large Multiamaller vesicles

High Shear fragmentation ‘fence press’

Solvent injection method

  • injection of water immiscible solvent

    • ether infusion

  • injection of miscible solvent

    • Ethanol injection

Targeted Liposomes

  • Include Ligands, antibodies, immunoglobulins, and oligosaccharides attached to the surface

Cationic Liposomes

  • Cationic lipid component interact with negatively charged DNA
    Results into Lipid- DNA complexes

Marketed Liposomes

  • Cancer Therapy (Myocet)

  • Fungal Diseases (Abeclet)

  • Analgesics (Diprivin)

  • Viral Vaccines (Epaxal)

  • Phtotdynamic therapy (Visudyne)

Liposomal Formulations Present in Clinical Trials

  1. Doxil, administered Via I.V, Ovarian, breast cancer, and Sarcoma

  2. Myocet, I.V, Combination therapy

  3. DepoDur, Epidural, Pain mamagment

  4. Amphocet, I.V, server fungal infections

  5. Mepact, i.v, High-grade

Factors affecting drug Release

  • Solvents

  • pH

  • Temperature

  • Agitation

  • Enzymes

  • Cell culture

  • Sink conditions

  • Volume

  • Sampling Interval

Formulations of Liposomal Anti-cancer Agents Clinically Tested

  • Regional Therapy

    • DepoCyt (intrathecal)