Wk 12: Niosomes + liposomes Flashcards
Outline the manufacturing process for liposomes + niosomes
- Phospholipid/nonionic surfactant, 2nd amphiphilic compound + cholesterol dissolved in organic solvent
- Solvent evaporated under heat
- Dry lipid film formed on surface
- The vessel is hydrated + aqueous buffer solution w/ drug added
- Vessel is shaken/sonicated at temp above phase transition temp
- Multi-lamellar vesicle formed
How are multilamellar vesicles turned into uni-lamellar vesicles?
- Ultra sound
- Pressure filtration
- Dialysis
ULVs contain entrapped drug molecules, however the aqueous medium also hold unentrapped drugs. How are the unentrapped drugs removed?
- Size exclusion chromatography
- Gel chromatography
- Dialysis
Outline how drugs are directly encapsulated in liposomes and niosomes
- 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
What are factors that influence chemical properties of niosomes?
- Hydration temp
- Nature of drug
- Choice of main surfactant
- Nature of membrane additive
- Addition of kinetic energy during prep
- Size reduction technique
What are the areas of potential use of niosomes + liposomes?
- Parental
- Pulmonary
- Oral of peptides
- Ophthalmic prep
What are the benefits of using liposomes or niosomes to encapsulate drugs?
- Solubilisation of drugs
- Drug release is modifiable
- Site avoidance
- Site directed targeting
- Clearance by RES
What are the pharmaceutical applications of liposomes?
- Retinoid
- Minoxidil
What are retinoids?
- For acne
- Teratogenic if given orally
How are liposomal topical formulations of retinoids better?
Red oxidation + skin irritations (due to slow release of drug)
What is minoxidil?
For hair loss due to infection
What are the problems of liposomal preparations of minoxidil?
Slow growth of liposomes during storage = instability
How is liposomal amphotericin B better than amphotericin B?
- Amphotericin B = renal toxicity
- Liposomal: targets liver + spleen reducing renal toxicity
Define pro-liposomes
- Dry free flowing solid drug products w/ dispersed system that form liposomal suspension in contact w/ aqueous phase
- For parenteral admin, oral, pulmonary + transdermal
What are the usual carrier systems of pro-liposomes?
- Sodium chloride
- Sugar: trehalose, sorbitol + mannitol
What are the advantages of pro-liposomes?
- Help w/ Aggregation, sedimentation, drug leakage + hydrolysis/oxidation
- Improve oral delivery as able to retain integrity
- Stable
- Scale-up production
- Prolonged half life
How are particulate based pro-liposomes manufactured?
- Sugar particles (300-500um), phospholipid, cholesterol + drug in chloroform
- Evaporation of solvent in rotary evaporator
- Prod dry powder
How are alcohol based pro-liposomes manufactured?
- 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
Which drugs can be incorporated into pro-liposomes?
- Hydrophobic drugs
- Chemotherapeutic drugs
- Antimicrobial drugs
What are the characterisation methods for pro-liposomes?
- Morphological properties
- Particle size + charge before/after reconstitution
- Flow properties
- Uniformity
- Encapsulation efficiency
- Thermal analysis
- Cytotoxicity to specific cells
- In vitro drug release
Give examples of a niosome containing cytotoxic drug
Doxorubicin + 5-fluorouracil
Give examples of advanced liposomal formulations
- mNon conventional
- PEGylated
- Immunoliposomes based cancer therapeutics
- PEGylated immunoliposomes w/ cytotoxic drugs
Define pH sensitive liposomes
Phase transition in alkaline media lead to inc membrane fluidity + release of encapsulated materials
Define heat sensitive liposomes
Leak more readily at temp above phase transition - release upon hyperthermia
Define PEGylated liposomes
Surface of vesicles modified w/ hydrophilic polymers, reducing agglomeration tendency of vesicles + avoid removal by RES
What is used for second line treatment for ovarian cancer?
Paclitaxel - PEGylated liposomal doxorubicin + topotecan
What are immunoliposomes?
Antibody conjugated liposomes - when conjugated w/ monoclonal antibodies, entrapped drug released into target cells
What are the properties of negatively charged liposomes?
More rapidly removed from circulation than neutral or +vely charged liposome
How can liposomal uptake be reduced?
Sterically stabilised additives - hydrophilic polymers or glycolipids
