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?