Transcript
LIPOSOMES IN DRUG TARGETINGBY: El-Hajqassem Hussien
EL-Hahabi HasanSUPERVISION: Dr. Mouhamed Koder
How this thesis was built up?
•Main Idea• Backbone• References and Translation• Challenges• Dr. M. Khoder Help
#References
# Translators
THESIS’S BOOK CONTENTS:• Chapter1: Preface 3 pages• Chapter2: Targeting Strategies 20 pages
• Active and passive Targeting• Cellular Targets• Carriers used in Targeting
• liposomes
• Chapter3: Liposomes components 22 pages• Surfactant study (PL)
• Chapter4: Liposomes preparations 13 pages• Chapter5: Liposomes Generations 17 pages• Chapter6: Medical application of liposomes 13 pages
102 pages Including
references
PRESENTATION CONTENTS1. Sophisticated Drugs
Problems…..2. How to solve it?
3. Fusion of ideas (carriers and Targeting)4. Liposomes
5. Liposomes prepration
ESTIMATED MAX TIME: 20 MIN
2.1. Carriers 2.2 Targeting
4.1 liposomes components4.2 liposomes Features4.3 liposomes generation and medical uses4.4 other types of liposomes
5.1 General Method5.2 Bangham Method
1. PREFACE
1. Sophisticated Drugs Problems…..
• Effective drugs but highly toxic or Narrow Theraputic Window• Stability Issues• Bioavailability Issues (solubility)• Half Time
• ex: Anticacancer• Gene therapy• Some AB
PLUS:• These Drugs are given in Tarditional Methods of
administration
SERandom Distribution
EX: COMBRETASTATI A4can’t be Adminstrated as a free drug !
2. HOW TO SOLVE IT?First: let’s deal with
low BA low StabilityNarrow TWShort half time ?
2.1. CARRIERS
Carriers Function
2.1.1 CARRIERS FUNCTION
• Help to bypass the natural barriers. • Improve BA
• Reduce Exposure to external media• Improve Stability
• Bound to Drug or entrape it• Improves Half time
liker DrugCarriers
Carrier
drug
drug
drug
drug
drugModifies drug PK not just in
absorption but Distribution as well.
2.1.2 CARRIERS TYPES
Colloidal carriersCellular CarriersPolymeric Carriers
Vesicular Carriers
Particulate Carriers
Liposomes
Niosomes
Virosomes
Nanoparticles
Microparticles
Released EC
ABs
Albumin
Radio-sensitive polymersMucus-Sticky
PolymersProteins
Supramolcular Carriers
Micelles
Lipoproteins
2.1.3 TARGEING USING CARRIES ALONE
• Could be used for passive targeting.• Depending on increased permeability• Local application• Immmune system targeting
Passive Targeting
RegularVasculature Tumor
Vasculature
STILL RANDOM DISTRIBUTION!!
WHAT TO DO TO SELECT SICK OTHER TARGETS?
Targeting some tumors and immune systems
2.2 TARGETING: THE MAGIC BULLET PRINCIPLE
2.2.1 MAIN POINT IN TARGETING: SPICIFIC ANTIGEN WHICH REPRESENT THE LOCK
Antigen
The Lock
2.2.2 THE KEY: LIGANDS Active Targeting
peptides
Carbohydrates
Growth Factors
Folate
3. FUSION OF IDEAS
• A carriers with it’s advantages and a Targeting moiety with result in:• Improved therapeutics response (+ drug
potency)• Improved BA• Improved Stability• Improved Half time• Reduced Toxicity• Reduced SE
CarrierCarrier
Target Cell
Ab
Ag
4. LIPOSOMES AS AN EXAMPLE
Lip- -somes
phosolipids
4.1 LIPOSOMES COMPONENTS
• PL (i.e. phosphatidylserine).
• Cholesterol, why?• Other components: …
4.2 LIPOSOMS FEATURES
• Biodegradable• Biocompatible• Non-toxic• Protect drug• modifies (Abs. and
Dis.)• Passive targeting• active targeting, how?
√√
√
√√
√
√
• Slow drug release• Uncontrolled drug
release• Entrapment efficacy• High cost• Some reached 13,00 $
per injection
• May expose Hydrolysis.
LIPOSOMES EVOLUTION
4.3 LIPOSOMES GENERATIONS AND MEDICAL USES
3 rd : Stealth targeting liposomes
2 ed: Stealth Liposomes1st Generation
3 rd : Stealth targeting liposomes
with penetrating peptides
4.3.1 FIRST GENERATION
• Targets immune system, why?• Medical uses:
• The most popular ex: Ambisome:…
Reticuloendothelial System
4.3.2 STEALTH LIPOSOMES
• Escapes phagocytosis > long circulating in the blood > better half time• Passive Targeting• Medical uses:• Doxurobucin stealth liposomes
4.3.3 TARGETED LIPOSOMES• Binds to conjugate• Some are modified with
penetrating peptides > increased amount at selected site.
• Medical uses: • Combretastati A4 Targeted
liposomes.• Folate-ligand liposomes
for treating leukimea.
)+potency) (-SE)
4.4 OTHER TYPES
OTHER VESICLES
4.4.1 Magnetic Liposomes• Treatment
4.4.2 LIPOLEXEX(LIPOSOMES+DNA COMPLEXES)• Positively charged lipids• Medical uses: • Gene delivery
4.4.3 VIROSOMES
• Used viruses to prepare vesicles.• influenza, herpes simples
• Lipid bilayer with Fusogenic proteins.• Improve fusion with target cells• Targetability to specific cells• Vaccination especially “influenza”
4.4.4 pH-sensitive Liposomes
OTHER VESICLES
OTHER VESICLES
4.4.5 Heamosomes
OTHER VESICLES
• 4.4.6 Liposomes for Diagnosis
5. LIPOSOMES PREPRATION
5.1 GENERAL METHOD OF PREPRATION
Lipid film prepration
Suspending this film in an aqueous media
Purification (from free and unentrapped drug)
Control of layers number and Sizing
5.2 BANGHAM METHOD AS AN EXAMPLE:
Liposomes
Hot water
Drying
PL Dissolution in
Organic solvent
5.3 LIPOSOMES STORAGE
No Light No O2 Reduce Hydrolysis
Best solution is: Lyphilization
FUTURE’S
Thanks for listening
Questions?
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