Liposomal Formation Flashcards
Why are nano carriers used?
they allow the deliver of small molecule drugs previously deemed to be less useful due to problems of
- stability
- solubility
- non-specific toxicity
What are liposomes?
are uni or multi-lamellar, highly ordered concentric bilayer structures alternating with aqueous compartments
- have lamellae
- are a phospholipid bilayer with an aqueous centre
How are drug solutes stored within a phospholipid bilayer?
hydrophilic solute is encapsulated in aqueous core between the bilayers
hydrophobic solute has an affinity towards the alkyl chains of the lipids/surfactants
- are embedded within the hydrophobic environment of the bilayer
What are the characteristics of a bilayer?
bilayers could be PEGylated
- INCREASES drug stability, drug circulation/half life, drug solubility and bioavailability
- DECREASES immunogenicity
vesicles can be attached with antibodies to achieve site specific delivery
What is the critical packing parameter?
determines the type of aggregate formed by surfactants
- bilayers have a CPP of 0.5-1
- hexagonal H1 phase have a CPP of <0.5
- hexagonal H11 phase have a CPP of >1
How does phase transition of temperature affect bilayer membrane characteristics?
in the gel phase
- there is both lipid chain conformational and translational order
in the liquid-crystalline phase
- there exists a conformational and translational disorder with lateral diffusibility
How are liposomes classified?
are classified based on the number of lamellae and size
small unilamellar vesicle (SUV) - presence of one bilayer
large unilamellar vesicle (LUV) - presence of bilayer
large multilamellar vesicles (MLV) - presence of more than one bilayer
multivesicular vesicles (MVV) - presence of multiple vesicles within a large vesicle
What are the methods of controlling vesicle size?
fractionation
centrifugation
- vesicles sediment in a centrifugal field
size exclusion chromatography
- vesicle suspensions are run through a column where large vesicles remain and small vesicles are eluted
What are the methods of controlling vesicle size?
homogenisation/sonication
high sheer homogenisers and probe sonicators are used to down size large vesicles
What are the methods of controlling vesicle size?
extrusion
polycarbonate membrane extrusion
- produces vesicles of defined size with narrow size distribution
ceramic extrusion
- use of ceramic membranes avoids the problem of membrane clogging
What are the methods of liposome preparation?
large multilamellar vesicles (LMV)
- thin film hydration method
- dehydration-rehydration method
large unilamellar vesicle (LUV)
- reverse phase evaporation method
small unilamellar vesicle (SUV)
- sanitation, extrusion, homogenisation
What are the factors affecting vesicle size, encapsulation and release characteristics?
solute
lipid/surfactant characteristics and concentration
cholesterol content
surface charge
method of preparation
osmotic effect
What is the EPR effect?
enhanced permeation and retention effect
- mechanism by which there is increased accumulation of macromolecules (liposomes and drugs) in tumour tissues
this is due to
- vasculature within tumours zones are leaky (underdeveloped and leaky endothelium) so drugs escape blood vessels
- dysfunctional lymphatic system results in a lack of lymphatic drainage so drugs remain for longer
What are liposomes?
liposomes are spherical lipid vesicles composed of one or more lipid bilayers (phospholipid)
- as a result of emulsifying natural or synthetic lipids in an aqueous medium
What are the function properties of liposomes?
protects the encapsulated drug from premature degradation
reduces side effects of the drug
potential to target the drug to a specific site in the body
relatively high drug accumulation at the site of action
increased shelf life and easier sterilisation
potential to engineer surface characteristics
What is Caelyx? Why is it known as STEALTH liposomal carrier? What are its properties?
Doxorubicin HCl liposome injection
- sterile, translucent, red liposomal dispersion
is known as a STEALTH lipsomal carrier due to it being PEGylated
- masks the presence of the liposome which allows it to achieve long circulation times
shows passive targeting by preferential accumulation in tumours due to EPR effect
What is amphotericin B?
is a polyene class of antifungals
- is a broad spectrum anti fungal
is amphoteric
- soluble in both acidic and basic environments
insoluble in water
- lipid formulations offer better therapeutic index
What are the different amphotericin B formulations?
Fungizone
- amphotericin B deoxycholate
Amphotec
- amphotericin B colloidal dispersion
Abelcet
- amphotericin B lipid complex
Ambisome
- liposomal amphotericin B
What are the properties of Fungizone?
amphotericin B deoxycholate
- given via intravenous infusion
- distributes quickly but penetrates poorly into CNS, saliva, bronchial secretions, pancreas, muscle and bone
- can cause glomerular nephrotoxicity
MOA
- binds to ergosterol within fungal cell membrane resulting in formation of pores due to depolarisation of the membrane
= pores permit leakage of monovalent ions (K, Na, H)
What are the properties of Amphotec?
amphotericin B colloidal dispersion
- formulation consists of amphotericin B in a complex with cholesterol sulphate
- has reduced rates of nephrotoxicity in comparison to Fungizone
What are the properties of Abelcet?
amphotericin B lipid complex
- equimolar concentrations of amphotericin and lipid
- has reduced frequency and severity of infusion related reactions
- has reduced rate of nephrotoxicity
What are the properties of Ambisome?
liposomal amphotericin B
- sterile, powder for solution for infusion that after reconstitution is given via intravenous infusion
- has reduced frequency and severity of infusion related reactions
- has reduced rate of nephrotoxicity
What is the difference between Abelcet and Ambisome?
abelcet - amphotericin B lipid complex
ambisome - liposomal amphotericin B
abelcet > ambisome
- caused higher rates of side effects at higher doses (chills, fevers, hypoxia)
- nephrotoxicity was higher with abelcet
