Wk 12: Niosomes + liposomes

Question 1

Outline the manufacturing process for liposomes + niosomes

Answer 1

1. Phospholipid/nonionic surfactant, 2nd amphiphilic compound + cholesterol dissolved in organic solvent
2. Solvent evaporated under heat
3. Dry lipid film formed on surface
4. The vessel is hydrated + aqueous buffer solution w/ drug added
5. Vessel is shaken/sonicated at temp above phase transition temp
6. Multi-lamellar vesicle formed

Question 2

How are multilamellar vesicles turned into uni-lamellar vesicles?

Answer 2

• Ultra sound
• Pressure filtration
• Dialysis

Question 3

ULVs contain entrapped drug molecules, however the aqueous medium also hold unentrapped drugs. How are the unentrapped drugs removed?

Answer 3

• Size exclusion chromatography
• Gel chromatography
• Dialysis

Question 4

Outline how drugs are directly encapsulated in liposomes and niosomes

Answer 4

• Lipophilic drug mixed w/ lipid + dissolved in organic solvent
• After rehydration, lipid drug molecule formed inside lipid bilayer
• If hydrophilic, drug molecules found in aqueous inner cavity of vesicles
• Amount depends on partition coefficient of drug btw water + lipid
• Drugs are dissolved in buffer used for rehydration of dried lipid film

= Poor entrapment efficiency

Question 5

What are factors that influence chemical properties of niosomes?

Answer 5

• Hydration temp
• Nature of drug
• Choice of main surfactant
• Nature of membrane additive
• Addition of kinetic energy during prep
• Size reduction technique

Question 6

What are the areas of potential use of niosomes + liposomes?

Answer 6

• Parental
• Pulmonary
• Oral of peptides
• Ophthalmic prep

Question 7

What are the benefits of using liposomes or niosomes to encapsulate drugs?

Answer 7

• Solubilisation of drugs
• Drug release is modifiable
• Site avoidance
• Site directed targeting
• Clearance by RES

Question 8

What are the pharmaceutical applications of liposomes?

Answer 8

• Retinoid
• Minoxidil

Question 9

What are retinoids?

Answer 9

• For acne
• Teratogenic if given orally

Question 10

How are liposomal topical formulations of retinoids better?

Answer 10

Red oxidation + skin irritations (due to slow release of drug)

Question 11

What is minoxidil?

Answer 11

For hair loss due to infection

Question 12

What are the problems of liposomal preparations of minoxidil?

Answer 12

Slow growth of liposomes during storage = instability

Question 13

How is liposomal amphotericin B better than amphotericin B?

Answer 13

• Amphotericin B = renal toxicity
• Liposomal: targets liver + spleen reducing renal toxicity

Question 14

Define pro-liposomes

Answer 14

• Dry free flowing solid drug products w/ dispersed system that form liposomal suspension in contact w/ aqueous phase
• For parenteral admin, oral, pulmonary + transdermal

Question 15

What are the usual carrier systems of pro-liposomes?

Answer 15

• Sodium chloride
• Sugar: trehalose, sorbitol + mannitol

Question 16

What are the advantages of pro-liposomes?

Answer 16

• Help w/ Aggregation, sedimentation, drug leakage + hydrolysis/oxidation
• Improve oral delivery as able to retain integrity
• Stable
• Scale-up production
• Prolonged half life

Question 17

How are particulate based pro-liposomes manufactured?

Answer 17

• Sugar particles (300-500um), phospholipid, cholesterol + drug in chloroform
• Evaporation of solvent in rotary evaporator
• Prod dry powder

Question 18

How are alcohol based pro-liposomes manufactured?

Answer 18

• Phospholipid, cholesterol and drug dissolved in 95% ethanol
• Ethanolic lipid solution containing drug produced
• Undergoes sonication
• Sucrose or mannitol suspended in solution
• Sonication again to deaggregate sugar
• Evaporation of ethanol: spray drying
• Prod dry pro-liposome powder

Question 19

Which drugs can be incorporated into pro-liposomes?

Answer 19

• Hydrophobic drugs
• Chemotherapeutic drugs
• Antimicrobial drugs

Question 20

What are the characterisation methods for pro-liposomes?

Answer 20

• Morphological properties
• Particle size + charge before/after reconstitution
• Flow properties
• Uniformity
• Encapsulation efficiency
• Thermal analysis
• Cytotoxicity to specific cells
• In vitro drug release

Question 21

Give examples of a niosome containing cytotoxic drug

Answer 21

Doxorubicin + 5-fluorouracil

Question 22

Give examples of advanced liposomal formulations

Answer 22

• mNon conventional
• PEGylated
• Immunoliposomes based cancer therapeutics
• PEGylated immunoliposomes w/ cytotoxic drugs

Question 23

Define pH sensitive liposomes

Answer 23

Phase transition in alkaline media lead to inc membrane fluidity + release of encapsulated materials

Question 24

Define heat sensitive liposomes

Answer 24

Leak more readily at temp above phase transition - release upon hyperthermia

Question 25

Define PEGylated liposomes

Answer 25

Surface of vesicles modified w/ hydrophilic polymers, reducing agglomeration tendency of vesicles + avoid removal by RES

Question 26

What is used for second line treatment for ovarian cancer?

Answer 26

Paclitaxel - PEGylated liposomal doxorubicin + topotecan

Question 27

What are immunoliposomes?

Answer 27

Antibody conjugated liposomes - when conjugated w/ monoclonal antibodies, entrapped drug released into target cells

Question 28

What are the properties of negatively charged liposomes?

Answer 28

More rapidly removed from circulation than neutral or +vely charged liposome

Question 29

How can liposomal uptake be reduced?

Answer 29

Sterically stabilised additives - hydrophilic polymers or glycolipids