Phospholipids

PolarHeadGroups

Threecarbonglycerol

What is a liposome?
Spherical vesicles with a phospholipid bilayer
Hydrophilic

Hydrophobic

Cell Membrane

Uses of Liposomes
Chelation therapy for treatment of heavy metal
poisoning
Enzyme replacement
Diagnostic imaging of tumors
Cosmetics
Study of membranes

Drug Delivery

Why Use Liposomes in Drug

Delivery?
Drug Targeting
Inactive: Unmodified liposomes gather in specific tissue
reticuloendothelial system
Active: alter liposome surface with ligand (antibodies,
enzymes, protein A, sugars)

Physical:temperature or pH sensitive liposomes

Directly to site

Why Use Liposomes in

Drug Delivery?
Pharmokinetics - efficacy and toxicity
Changes the absorbance and biodistribution
Deliver drug in desired form
Multidrug resistance

Protection
Decrease harmful side effects
Changewheredrugaccumulatesinthebody

Protectsdrug

Why Use Liposomes in

Drug Delivery?
Release
Affect the time in which the drug is released
Prolong time -increase duration of action and
decrease administration
Dependentondrugandliposomeproperties
Liposomecomposition,pHandosmoticgradient,and
environment

Modes of Liposome/Cell
Interaction
Adsorption

Endocytosis

Fusion

Lipid
transfer

Classes of Liposomes
Conventional

Long circulating

Immuno

Cationic

Liposomes Help Improve

Therapeutic index
Rapid metabolism
Unfavorable pharmokinetics
Low solubility
Lack of stability
Irritation

Custom design

Lipid content
Size
Surface charge
Method of preparation

Current liposomal drug

preparations
TypeofAgents
AnticancerDrugs
Antibacterial
Antiviral
DNAmaterial
Enzymes
Radionuclide
Fungicides
Vaccines

Examples
Duanorubicin, Doxorubicin*,Epirubicin
Methotrexate,Cisplatin*,Cytarabin
Triclosan,Clindamycinhydrochloride,
Ampicillin,peperacillin,rifamicin
AZT
cDNACFTR*
HexosaminidaseA
Glucocerebrosidase,Peroxidase
In111*,Tc99m
AmphotericinB*
Malariamerozoite,Malariasporozoite
HepatitisBantigen,Rabiesvirusglycoprotein

*CurrentlyinClinicalTrialsorApprovedforClinicalUse

LiposomalFormulationofAmB
Phospholipid:AmBratio

AmB

Cholesterolonlyfew%moles

Lipid

ExactMechanismofliposomesnotunderstood
Diffusion
Lipidtransfer

Decreaseintoxicity
Nodecreaseineffectivenessofdrugagainstfungi

Problems with Liposomal

Preparations of Drugs
$$$$
Fungizone $40.58
Amphotec $2334
Doxil $1200 per treatment, twice the cost of normal protocol
of chemotherapy and drugs

Lacklongtermstability(shortshelflife)
Physicalandchemicalinstability
FreezedryandpHadjustment

LowPayLoadpoorencapsulation
Polardrugsanddrugswithoutoppositecharge
Modifications

Problemscontinued
Possibilityofnewsideeffects
Doxilhandandfootsyndrome

Efficacy
CFTR

Future
Studieswithinsulinshowthatliposomesmay
beaneffectivewaytopackageproteins
andpeptidesforuse
ClinicalTrialsforseveralliposomalformulations
Morestudiesonthemanipulationofliposomes

Journals

Allen,TheresaM."LiposomalDrugFormulations:RationaleforDevelopmentandWhatWeCan
ExpectfortheFuture."Drugs56:747756,1998.
Allen,TheresaM."Longcirculating(stericallystabilized)liposomesfortargeteddrugdelivery."
TiPs15:214219,1994.
Allen,TheresaM."OpportunitiesinDrugDelivery."Drugs54Suppl.4:814,1997
Janknegt,Robert."LiposomalandLipidFormulationsofAmphotericinB."ClinicalPharmacokinetics.
23(4):279291,1992.
Kim,Annaetal."Pharmacodynamicsofinsulininpolyethyleneglycolcoatedliposomes."
InternationalJournalofPharmaceutics.180:7581,1999.
Quilitz,Rod."OncologyPharmacotherapy:TheUseofLipidFormulationsofAmphotericinBinCancer
Patients."CancerControl.5:439449,1998.
Ranade,VasantV."DrugDeliverySystems:SiteSpecificDrugDeliveryUsingLiposomesasCarriers."
Pharmacology.29:685694,1989.
Storm,GertandDaanJ.A.Crommelin."Liposomes:quovadi?"PSTT1:1931,1998.
Taylor,KMGandJMNewton."Liposomesasaveciclefordrugdelivery."BritishJournalofHospital
Medicine.51:5559,1994

Websites

James,JohnS."DoxilApprovedforKS."www.immunet.org.imminet/atn.nsf/page/a23503.
Wasan,Ellen."TargetedGeneTransfer."Member.tripod.com/~rrishna/lipos1.html
"IntroductiontoControlledDrugDeliverySystems."www5.bae.ncsu.edu/bae/reearch/blak
k/otherprojects/drugDeliver_97/
http://www.Mssm.edu/medicine/thrombosis/phosphol.html
"Doxorubicin."http://tirgan.com/adria.htm
"ClinicalPharmacologyOnline."http://www.cponline.gsm.com/scripts/fullmono/showmono.
"Drugstore.com"http://www.drugstore.com/pharmacy/prices/Amphotec.
"Sequus'DoxilBecomesFirstLiposomeProductApprovedInU.S."www.slip.net/~mcdavis/
database/doxor_1
"Liposomes."www.collabo.com/liposom0.htm
Paustin, Timothy. Cellular Membranes.www.bact.wisc.edu/microtextbook/bacterialstructure/Membranegen.html
www.cbc.umn.edu/~mwd/cell_www/chapter2/membrane.html#PHOSPHOLIPIDS

Books

Jones,MacolmN.andChapman,David.Micelles,MonolayersandBiomembranes.WileyLiss.
NewYork(1995).

Garrett,R.andGrishamC.Biochemistry,2nded.SaundersCollegesPublishing.NewYork(1999).264.