Liposomes as carriers of anticancer drugs in drug delivery ... (poster).pdf · nanoparticles and...
1
RESEARCH POSTER PRESENTATION DESIGN © 2015 www.PosterPresentations.com RESEARCH POSTER PRESENTATION DESIGN © 2015 www.PosterPresentations.com Introduction: Nowadays, cancer is one of the most important issues in global health and for the time being, it is one of the reasons for 12%of all deaths worldwide. some scientific research has been done in the cause of cancer ،its recognition, and medical treatment up to now. But unfortunately due to the increasing of resistance of the cancer cells against the chemotherapy drugs, the attempts ended in failure. For this reason, scientists are looking for the methods to increase the response to the cancer cells to anticancer drugs and also find the best methods with less side effects. Currently, the usage of liposomes are notable as one of the most famous and the most stable nanocarriers in drug delivery system. Liposomes are colloidal substances with two or more phospholipid membrane which are created by the mixture of lipids and other amphipathic molecules such as cholesterol. Common medicinal compounds that use of liposome for defeating in cancer disease, including Doxil and Evacet that both of them consist of chemotherapic drug “doxorubicin”. To design an efficient nanocarrier for drug delivery system, we should consider the actions to maximize performance and prolong liposome circulation time in the blood stream such as the ability to protect it from immune system ,the way that exhibits greater stability and diminished toxicity of liposomes and target the area of the purpose tissue in the body and release drugs in a controlled manner. Methods: All the methods of preparing the liposomes involve four basic stages:1-Drying down lipids from organic solvent. 2- Dispersing the lipid in aqueous media. 3- Purifying the resultant liposome. 4- Analyzing the final product. The following methods are used for the preparation of liposome based on drug loading:1-Passive loading techniques 2-Active loading technique. Passive loading techniques include three different methods: 1-Mechanical dispersion method. 2-Solvent dispersion method. 3-Detergent removal method Results and discussion: Despite the many disadvantages of liposomes as drug carrier like high production cost, low efficiency in trapping the drugs and slow drug release, they have lots of benefits. Liposomes are non-toxic, flexible, biocompatible, completely biodegradable, and they help reduce the exposure of sensitive tissues to toxic drugs Conclusion: Despite the limitations and drawbacks that exist today, science and research go towards the use of nanocarriers and drug delivery system for the treatment of cancer and it is hoped that in the near future drug delivery systems, will be problem solver of treatment of many patients with incurable diseases. Abstract Nano particle in drug delivery systems Organic nanoparticles polymeric nanoparticle homopolymers nanospheres nanocapsules Hydrogels nanoparticles dendrimers copolymers micelles polymerosomes lipid nanoparticle s Solid lipid nanoparticles liposomes micelles Inorganic nanoparticles Ceramic nanoparticles fullerenes nanoparticles Metallic nanoparticles Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran Samaneh mirhaji Liposomes as carriers of anticancer drugs in drug delivery systems These vesicles consist of several lipid bilayers separated from one another by aqueous spaces. These entities are heterogeneous in size, often ranging from a few hundreds to thousands of nanometers in diameter. These vesicles consist of a single bilayer surrounding the entrapped aqueous space having diameters larger than 100 nm Small unilamellar vesicles consist of a single bilayer surrounding the entrapped aqueous space having size range less than 100 nm Multi lamellar vesicles Large unilamellar vesicles Small unilamellar vesicles unique properties of PEG • Nontoxic • soluble in both polar and nonpolar solvents • can be eliminated from the body through a combination of renal and hepatic pathways effect of the PEG corona • cause significant stabilization of liposome dispersions • prevent liposome aggregation • inhibit protein and cellular interactions with liposomes • considerable increase in the loading efficiency of the liposomes for hydrophobic molecules • The permeability of PEGylated liposomes was decreased in comparison to DPPC liposomes without PEGylation. • alter the properties of phospholipid membranes. • increase in the hydrophobicity of lipid membranes. Retinol palmitate A plot of change in absorbance at 540nm with time for incubation of : a)retinol b)retinol palmitate c)control with erythrocyte in phosphate buffered saline at 37 C . Inset :absorption spectrum of erythrocyte after lysis by retinoids A plot change in absorbance at 540 nm with time for incubation of a)retinol in phosphate buffered- saline b) PC liposome. c) PC liposomes with erythrocyte at 37 C Effect of liposomal and non-liposomal retinol and retinol palmitate on red blood cells (RBC) the liposomes can sequester the drug and prevent its interaction with erythrocytes Effects of liposomal and nan liposomal retinol palmitate on erythrocyte’s viscosity Change of viscosity with shear rate. a)Erythrocyte b)Erythrocyte and retinol palmitate c)Erythrocyte and PC-liposomal. the presence of an external lipid, the lipids of RBC get exchanged with the former, and as a result, the rigidity of the red cells decreases. Consequently,decrease in the viscosity is observed. Biophysical Chemistry 73 Ž1998. 155 162 -Liposome encapsulated vitamin A compounds exhibit greater stability and diminished toxicity /Anil K. Singh , Joydip Das Biophysical Chemistry 73 Ž1998. 155 162 -Liposome encapsulated vitamin A compounds exhibit greater stability and diminished toxicity /Anil K. Singh , Joydip Das Classification of Liposome Based on size and number of bilayers Improved penetration into tissues Site-specific targeting Improved transfer of hydrophilic, charged molecules Improved solubility of lipophilic and amphiphilic drugs Site-avoidance mechanism Passive targeting to the cells of the immune system, (mononuclear phagocytic system ) Benefits of drug load in liposomes Amphotericin B, hydrophilic drugs, such as anticancer agent doxorubicin or acyclovir amphotericinB, porphyrins, vaccines, Doxorubicin amphotericin B Anti-inflammatory drugs, anti-cancer, anti-infection Antibiotics, chelators, plasmids, and genes Corticosteroids, anesthetics, and insulin Methods of liposome preparation Drying down lipids from organic solvent Dispersing the lipid in aqueous media. Purifying the resultant liposome Analyzing the final product General methods of preparation Trends and Developments in Liposome Drug Delivery Systems TIANSHUN LIAN, RODNEY J. Y. HO Benefits of drug load in liposomes Methods of liposome preparation Method of liposome preparation and drug loading Liposome preparation based on drug loading Passive loading techniques Mechanical dispersion method Solvent dispersion method Detergent removal method Active loading technique For drugs with amphipathic feature xenobiotic opsonins Reference 1. A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells/Biochimica et Biophysica Acta 1237(1995) 99-108 2. Liposome encapsulated vitamin A compounds exhibit greater stability and diminished toxicity/Biophysical Chemistry 73 Ž1998. 155 162 3. PEGylated Liposomes as Carriers of Hydrophobic Porphyrins /Monika Dzieciuch,† Sami Rissanen,‡ Natalia Szydłowska, 4. Combination Approach: the Future of the War Against Cancer Lan Chen • Anshoo Malhotra /DOI 10.1007/s12013- 015-0549-0 5. The role of surface charge and hydrophilic groups on lipos0me clearance in vivo - Alberto Gabizon Why liposome should be PEGylated? although liposomes show remarkable promise as drug carriers, they do have a significant weakness: once injected into the bloodstream, they are vulnerable to attack from the reticuloendothelial system (RES). circulation time can be increased by decreasing liposome size and modifying the surface/steric effect with PEG derivatives. Remove Liposome from the blood stream RES opsonization introduction result result Effect of pegylation on liposome Amphipathic phospholipids property creates spherical particles in water environment which called liposomes. liposome drug delivery systems have played a remarkable role in the formulation of potent drugs to improve therapeutics. Depending on whether the molecule (drug) is hydrophilic or hydrophobic, it could be incorporated in the entrapped aqueous interior or in the lipid bilayer of the liposome. Liposomes are prepared with distinct structure, size, composition, flexibility with a variety of surface modification. Such availability of liposomes with great diverse properties makes them most intelligent carrier system for delivery of bioactive substances discussion Nowadays the knowledge of using nanoparticles and drug delivery system is progressing and Despite the limitations and drawbacks that exist today, science and research go towards the use of drug delivery system based on liposome carrier in many kinds of field such as cancer therapy, vaccine delivery , pulmonary delivery, gene Therapeutics , ophthalmic drug delivery etc. it is hoped that in the near future we can treat many disease and patient problem with this intelligent drug delivery systems Conclusion Carrier Name of the product Drug Non PEGylated liposome Daunoxome Daunorubicin Non PEGylated liposome Myocet Doxorubicin PEGylated liposome Doxil/Caelyx Doxorubicin Liposomes are colloidal particles that can be prepared with phospholipid molecules. Phospholipids are amphipathic molecule i.e. having affinity for both aqueous & polar moieties, as they have a hydrophobic tail & hydrophilic head. Depending on whether the molecule(drug) is hydrophilic or hydrophobic, it could be incorporated in the entrapped aqueous interior or in the lipid bilayer of the liposome
Transcript of Liposomes as carriers of anticancer drugs in drug delivery ... (poster).pdf · nanoparticles and...
RESEARCH POSTER PRESENTATION DESIGN © 2015
www.PosterPresentations.comRESEARCH POSTER PRESENTATION DESIGN © 2015
www.PosterPresentations.com
Introduction: Nowadays,cancerisoneofthemostimportantissuesinglobalhealthandforthetimebeing,itisoneofthereasonsfor12%ofalldeathsworldwide.somescientificresearchhasbeendoneinthecauseofcancer ،itsrecognition,andmedicaltreatmentuptonow.Butunfortunatelyduetotheincreasingofresistanceofthecancercellsagainstthechemotherapydrugs,theattemptsendedinfailure.Forthisreason,scientistsarelookingforthemethodstoincreasetheresponsetothecancercellstoanticancerdrugsandalsofindthebestmethodswithlesssideeffects.Currently,theusageofliposomesarenotableasoneofthemostfamousandthemoststablenanocarriersindrugdeliverysystem.Liposomesarecolloidalsubstanceswithtwoormorephospholipidmembranewhicharecreatedbythemixtureoflipidsandotheramphipathicmoleculessuchascholesterol.Commonmedicinalcompoundsthatuseofliposomefordefeatingincancerdisease,includingDoxilandEvacetthatbothofthemconsistofchemotherapicdrug“doxorubicin”.Todesignanefficientnanocarrierfordrugdeliverysystem,weshouldconsidertheactionstomaximizeperformanceandprolongliposomecirculationtimeinthebloodstreamsuchastheabilitytoprotectitfromimmunesystem,thewaythatexhibitsgreaterstabilityanddiminishedtoxicityofliposomesandtargettheareaofthepurposetissueinthebodyandreleasedrugsinacontrolledmanner.Methods: Allthemethodsofpreparingtheliposomesinvolvefourbasicstages:1-Dryingdownlipidsfromorganicsolvent.2- Dispersingthelipidinaqueousmedia.3- Purifyingtheresultantliposome.4- Analyzingthefinalproduct.Thefollowingmethodsareusedforthepreparationofliposomebasedondrugloading:1-Passiveloadingtechniques2-Activeloadingtechnique.Passiveloadingtechniquesincludethreedifferentmethods:1-Mechanicaldispersionmethod.2-Solventdispersionmethod.3-DetergentremovalmethodResultsanddiscussion: Despitethemanydisadvantagesofliposomesasdrugcarrierlikehighproductioncost,lowefficiencyintrappingthedrugsand slowdrugrelease,theyhavelotsofbenefits.Liposomesarenon-toxic,flexible,biocompatible,completelybiodegradable,andtheyhelpreducetheexposureofsensitivetissuestotoxicdrugsConclusion:Despitethelimitationsanddrawbacksthatexisttoday,scienceandresearchgotowardstheuseofnanocarriersanddrugdeliverysystemforthetreatmentofcanceranditishopedthatinthenearfuturedrugdeliverysystems,willbeproblemsolveroftreatmentofmanypatientswithincurablediseases.
Abstract
Nanoparticleindrugdeliverysystems
Organicnanoparticles
polymericnanoparticle
homopolymers
nanospheres
nanocapsules
Hydrogelsnanoparticles
dendrimers
copolymers
micelles
polymerosomes
lipidnanoparticle
s
Solid lipidnanoparticles
liposomes
micelles
Inorganicnanoparticles
Ceramicnanoparticles
fullerenesnanoparticles
Metallicnanoparticles
InstituteofBiochemistryandBiophysics,UniversityofTehran,Tehran,IranSamanehmirhaji
Liposomesascarriersofanticancerdrugsindrugdeliverysystems
Thesevesiclesconsistofseverallipidbilayersseparatedfromoneanotherbyaqueousspaces.Theseentitiesareheterogeneousinsize,oftenrangingfromafewhundredstothousandsofnanometersindiameter.
Thesevesiclesconsistofasinglebilayersurroundingtheentrappedaqueousspacehavingdiameterslargerthan100nm
Smallunilamellarvesiclesconsistofasinglebilayersurroundingtheentrappedaqueousspacehavingsize
rangelessthan100nm
Multilamellarvesicles
Largeunilamellarvesicles
Smallunilamellarvesicles
uniquepropertiesofPEG• Nontoxic• soluble in both polar and nonpolar solvents• can be eliminated from the body through a combination of
renal and hepatic pathways
effectofthePEGcorona• cause significant stabilization of liposome dispersions• prevent liposome aggregation• inhibit protein and cellular interactions with liposomes • considerableincreaseintheloadingefficiencyoftheliposomesforhydrophobicmolecules
• ThepermeabilityofPEGylatedliposomeswasdecreasedincomparisontoDPPCliposomeswithoutPEGylation.
• alterthepropertiesofphospholipidmembranes.• increaseinthehydrophobicityoflipidmembranes.
Retinolpalmitate
Aplotofchangeinabsorbanceat540nmwithtimeforincubationof:a)retinolb)retinolpalmitatec)controlwitherythrocyteinphosphatebufferedsalineat37C.Inset:absorptionspectrumoferythrocyteafterlysisbyretinoids
Aplotchangeinabsorbanceat540nmwithtimeforincubationofa)retinolinphosphatebuffered-salineb)PCliposome.c)PCliposomeswitherythrocyteat37C
Effectofliposomal andnon-liposomalretinol andretinolpalmitateonredbloodcells(RBC)
theliposomescansequesterthedrugandpreventitsinteractionwitherythrocytes
Effectsofliposomalandnanliposomalretinolpalmitateonerythrocyte’sviscosity
Changeofviscositywithshearrate.a)Erythrocyteb)Erythrocyteandretinolpalmitatec)ErythrocyteandPC-liposomal.
thepresenceofanexternallipid,thelipidsofRBCgetexchangedwiththeformer,andasaresult,therigidityoftheredcellsdecreases.Consequently,decreaseintheviscosityisobserved.
BiophysicalChemistry73Z1998.155162-LiposomeencapsulatedvitaminAcompoundsexhibitgreaterstabilityanddiminishedtoxicity/AnilK.Singh,JoydipDasBiophysicalChemistry73Z1998.155162-LiposomeencapsulatedvitaminAcompoundsexhibitgreaterstabilityanddiminishedtoxicity/AnilK.Singh,JoydipDas
ClassificationofLiposomeBasedonsizeandnumberofbilayers
Improvedpenetrationinto
tissues
Site-specifictargeting
Improvedtransferofhydrophilic,charged
molecules
Improvedsolubilityoflipophilicandamphiphilicdrugs
Site-avoidancemechanism
Passivetargetingtothecellsoftheimmunesystem,(mononuclearphagocytic
system)BenefitsofdrugloadinliposomesAmphotericinB,
hydrophilicdrugs,suchasanticanceragentdoxorubicinoracyclovir
amphotericinB,porphyrins,vaccines, Doxorubicin
amphotericinB
Anti-inflammatorydrugs,anti-cancer,anti-infection
Antibiotics,chelators,plasmids,andgenes
Corticosteroids,anesthetics,andinsulin
Benefits of drug load in Liposomes Methodsofliposomepreparation
Dryingdownlipidsfromorganicsolvent
Dispersingthelipidinaqueousmedia.
Purifyingtheresultantliposome
Analyzingthefinalproduct
Generalmethodsofpreparation
TrendsandDevelopmentsinLiposomeDrugDeliverySystemsTIANSHUNLIAN,RODNEYJ.Y.HO
Benefitsofdrugloadinliposomes Methodsofliposomepreparation
Methodofliposomepreparationanddrugloading
Liposomepreparation
basedondrugloading
Passiveloadingtechniques
Mechanicaldispersionmethod
Solventdispersionmethod
Detergentremovalmethod
Activeloadingtechnique
Fordrugswithamphipathic
feature
xenobiotic
opsonins
Reference1. A new strategy for attachment of
antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells/Biochimica et BiophysicaActa 1237(1995) 99-108
2. Liposome encapsulated vitamin A compounds exhibit greater stability and diminished toxicity/Biophysical Chemistry 73 Ž1998. 155 162
3. PEGylated Liposomes as Carriers of Hydrophobic Porphyrins /Monika Dzieciuch,† Sami Rissanen,‡ Natalia Szydłowska,
4. Combination Approach: the Future of the War Against Cancer Lan Chen • AnshooMalhotra /DOI 10.1007/s12013-015-0549-0
5. The role of surface charge and hydrophilic groups on lipos0me clearance in vivo -Alberto Gabizon
WhyliposomeshouldbePEGylated?
althoughliposomesshowremarkablepromiseasdrugcarriers,theydohaveasignificantweakness:onceinjectedintothebloodstream,theyarevulnerabletoattackfromthereticuloendothelialsystem(RES).circulationtimecanbeincreasedbydecreasingliposomesizeandmodifyingthesurface/stericeffectwithPEGderivatives.
RemoveLiposomefromthebloodstream
RESopsonization
introduction
result
result
EffectofpegylationonliposomeAmphipathicphospholipidspropertycreatessphericalparticlesinwaterenvironmentwhichcalledliposomes.liposomedrug
deliverysystemshaveplayedaremarkableroleintheformulationofpotentdrugstoimprovetherapeutics.Dependingon
whetherthemolecule(drug)ishydrophilicorhydrophobic,itcouldbeincorporatedintheentrappedaqueousinteriororinthelipidbilayeroftheliposome.Liposomesarepreparedwithdistinctstructure,size,composition,flexibilitywithavarietyofsurfacemodification.Suchavailabilityofliposomeswithgreatdiverseproperties
makesthemmostintelligentcarriersystemfordeliveryofbioactivesubstances
discussionNowadaystheknowledgeofusingnanoparticlesanddrugdeliverysystemisprogressingandDespitethelimitationsanddrawbacksthatexisttoday,scienceand
researchgotowardstheuseofdrugdeliverysystembasedon
liposomecarrierinmanykindsoffieldsuchascancertherapy,vaccinedelivery,pulmonarydelivery,geneTherapeutics,
ophthalmicdrugdeliveryetc.itishopedthatinthenearfuturewe
cantreatmanydiseaseandpatientproblemwiththis
intelligentdrugdeliverysystems
Conclusion
Carrier Nameoftheproduct
Drug
NonPEGylatedliposome
Daunoxome Daunorubicin
NonPEGylatedliposome
Myocet Doxorubicin
PEGylatedliposome
Doxil/Caelyx Doxorubicin
Liposomesarecolloidalparticlesthatcanbepreparedwithphospholipidmolecules.Phospholipidsareamphipathicmoleculei.e.havingaffinityforbothaqueous&polarmoieties,astheyhaveahydrophobictail&hydrophilichead.Dependingonwhetherthemolecule(drug)ishydrophilicorhydrophobic,itcouldbeincorporatedintheentrappedaqueousinteriororinthelipidbilayeroftheliposome
