A SEMINAR ON LIPOSOME DRUG DELIVERY FOR

OPHTHALMICS

PRESENTED BY-Mr. Mayur R. WaghM.Pharm 1ST Sem

(PHARMACEUTICS)

GUIDED BY-Dr. (Mrs.) Pallavi

Chaudhari

Dr. D.Y. Patil College of Pharmacy, Akurdi, Pune-44

09/11/2016

2

CONTENTS-• DEFINATION OF LIPOSOMES• CLASSIFICATION OF LIPOSOMES• ADVANTAGES & DISADVANTAGES OF

LIPOSOMES• OCULAR DRUG DELIVERY SYSTEM• VESICULAR OCULAR DRUG DELIVERY SYSTEM

OF LIPOSOMES• APPLICATIONS OF LIPOSOMES• REFRENCES

3

INTRODUCTION OF LIPOSOMES:- Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids

Liposomes were discovered about 40 years ago by Alec Bangham

4

• Liposomes can be produced from cholesterols, non toxic surfactants, sphingolipids, glycolipids, long chain fatty acids & even membrane proteins

• Liposomes are the drug carrier loaded with great variety of molecules such as small drug molecules, proteins, nucleotides & even plasmids

• Considerable progress was made during 1970s and 1980s in the field of liposome stability leading to long circulation times of liposomes

INTRODUCTION-

5

STRUCTURAL COMPONENTS :

6

CLASSIFICATION:VESICLE TYPE  ABBREVIATI

ONDIAMETER SIZE

NO. OF LIPID BI - LAYER

Unilamellar vesicle UV All size range ONE

Small unilamellar vesicle SUV 20-100 nm ONE

 Medium unilamellar vesicle

MUV >100 nm ONE

Large unilamellar vesicle LUV >1000 nm ONE

Giant unilamellar vesicle

GUV >1µm ONE

Oligolamellar vesicle OLV 0.1-1µm 5

Multilamellar vesicle MLV >0.5µm 5-25

Multivesicular vesicle MV >1µm Multicompartmental structure

7

ADVANTAGES Drugs delivered intact to various

body tissues.

Liposomes can be used for both

hydrophilic and hydrophobic drug.

Possibility of targeting and

decrease drug toxicity.

The size, charge and other

characteristics can be altered

according to drug and desired

tissue.

DISADVANTAGESThey need many modification

for drug delivery to special

organs.

Stability problem and

oxidative degradation.

Requires special packaging

and storing facility.

Costly.

8

Liposomes in drug delivery:• Liposomes are microparticulate lipoidal vesicles

which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents

• Composed of relatively biocompatible and biodegradable material, and they consist of an aqueous volume entrapped by one or more bilayers of natural and/or synthetic lipids

• Drugs with widely varying lipophilicities can be encapsulated in liposomes, either in the Phospholipid bilayer or at the bilayer interface

9

Ideal Characteristics of Liposomes-

• It should be non-toxic, biocompatible, biodegradable

• Therapeutic amount of drug release

• Physicochemical stable in-vivo and in-vitro

• Drug release does not affect the drug action

10

OCULAR DRUG DELIVERY SYSTEM –

• Ocular administration of drug is associated with the need to treat ophthalmic diseases

• Eye is most easily accessible site for topical administration of medication

• Ideal ophthalmic drug delivery system is the one which is able to sustain the drug release and to remain in the vicinity of front of the eye for prolonged period of time

• Most ocular treatments call for the topical

administration of opthalmically active drugs to tissue around the ocular activity

11

Anatomy of the Eye-

12

ROUTES OF DRUG DELIVERY IN EYE-

13

Absorption barriers for topical drug delivery-

1. Corneal Barrier

2. Tear Film Barrier

3. Scleral Barrier

4. Conjunctival Barrier

14

Mechanisms of permeation of liposomes throughocular surface-

• The mechanisms of interaction of liposomes with cell membranes that result into intracellular drug delivery

• Four mechanisms of intracellular drug delivery by liposomes -:

1. Adsorption: Adsorption of liposomes to cell membrane is one of the important mechanisms of intracellular drug delivery

2. Endocytosis: Adsorption of liposomes on the surface of cell membrane is followed by their engulfment and internalization into endosomes

15

3. Fusion: Fusion of lipid bilayer of liposomes with lipoidal cell membrane by intermixing and lateral diffusion of lipids results in direct delivery of liposomal contents into the cytoplasm

4. Lipid exchange: Due to the similarity of liposomal membrane lipids with the cell membrane phospholipids, lipid transfer proteins in the cell membrane recognize liposomes and consequently cause lipid exchange.

• This results in the destabilization of liposomal membranes and intracellular release of drug molecules

Mechanisms of intracellular drug delivery by liposomes -:

16

Routes of drug Administration-

• Topical Administration-• Drops• Perfusion• Sprays•Ointments• Particulates

• Intraocular drug delivery-• Liposomes•Microparticulates and nanoparticles• Intraocular devices• Iontophoresis

17

FACTORS AFFECTING INTRAOCULAR BIOAVAILABILITY :-

1. Inflow & Outflow of Lacrimal fluids2. Efficient naso-lacrimal drainage3. Interaction of drug with proteins of Lacrimal fluid4. Dilution with tears5. Limited and poor corneal permeability 6. Metabolism

18

VESICULAR OCULAR DRUG DELIVERY SYSTEM – LIPOSOMES

• Deliver the drug at a predetermined rate and should release the drug at the specific site of action in therapeutically active concentration

• Drug delivery via vesicles provides prolonged as well as controlled drug delivery at the targeted corneal surface

• Thus, a vesicle acts as prominent carrier system for ophthalmic drug delivery

• Vesicular drug delivery systems entrap the drug molecule within the lipid bilayer or surfactant vesicles

19

• At the corneal surface of an eye also prevent the metabolism of the drug by the enzymes that are present at the tear/corneal epithelial surface

• Vesicles used in ophthalmic include liposome and niosomes specifically

• Liposome act as carrier system for the delivery of variety of drug molecules, proteins, nucleotides, enclosing them with a great potential for their application in ophthalmic

VESICULAR OCULAR DRUG DELIVERY SYSTEM – LIPOSOMES

They are having an intimate contact with the corneal and conjunctival surfaces

Which is desirable for drugs that are poorly absorbed, the drugs with low partition coefficient, poor solubility or those with medium to high molecular weights

20

21

• Liposomal encapsulation has the drug in the eye, but also to reduce the intraocular toxicity of certain drugs

• For example, liposome-encapsulated amphotericin B produces less toxicity than the commercial solubilized amphotericin B formulation when injected intravitreally

• Vesicle composed of phospholipid bilayer enclosing aqueous compartment in alternate fashion

• It is Biodegradable, Non-toxic in nature

VESICULAR OCULAR DRUG DELIVERY SYSTEM – LIPOSOMES-

22

• Applications of Liposomes In Ophthalmic Drug Delivery-:

• Subconjunctival injection of liposomes can provide retentive effect and steady-state release at the site of application E.g. Heparin

• It can enhance the permeation of poorly absorbed drug molecules by binding to the corneal surface and improving residence time E.g. Ciprofloxacin

• liposomes can improve pharmacokinetic profile, enhance therapeutic effect, and reduce toxicity associated with higher dose E.g. fluconazole

• liposomes have been widely investigated for the treatment of both anterior and posterior segment eye disorders.

23

PATENTS IN LIPOSOMAL DRUG DELIVERY(OCULAR)

TITLE AUTHOR NAME

PATENT NO.

PUBLICATION DATE

Liposome System For Ocular Administration

Subramanian Venkatraman, Sujay

Chattopaddhay. WO

2011098578A2

16 Feb. 2012

A Liposomal Formulation For Ocular Drug Delivery

Yian Chiang Freddy Boey, Tina Wong.

WO 20120211

07 A3

29 Nov. 2012

Liposomal Formulation For Ocular Drug Delivery

Jayaganesh V. Natranjan,

Subramanian Venkatraman

US 20130216

606A122 Aug.

2013

24