Niosomes and Liposomes

Question 1

what is the manufacturing process for liposomes and niosomes?

Answer 1

1-Phospholipid or non-ionic surfactant (and the second amphiphilic compound and a membrane fluidity modulator, cholesterol) are dissolved in an organic solvent.
2 Evaporation of the solvent under heat.
3 Dry lipid film formation on the surface of the vessel.
4 Aqueous buffer solution containing the drug is added and the vessel is subjected to sonication or shaking at temperatures above the phase transition temperature (Tc).
5 Multi-lamellar vesicles will form and a suspension containing the vesicles in aqueous liquid are formed.

Question 2

how do you form uni-lamellar vesicles from MLVs?

Answer 2

ultrasound
pressure filtration
dialysis

Question 3

what do we do to remove entrapped drug from aq medium in ULVs?

Answer 3

hence size exclusion chromatography, gel chromatography, or dialysis can be
applied to remove the unentrapped drug

Question 4

how do you entrap the drugs in liposomes/niosomes?

Answer 4

Lipophilic drug is mixed together with the lipids and dissolved in the organic solvent
➢After rehydration of the film, the lipid drug molecules are formed inside lipid bilayer
➢If the drug substance has some hydrophilic groups, some drug molecules will also be found in the aqueous inner cavity of the vesicles. The amount depends on the partition coefficient of the drug between water and lipid
➢Direct encapsulation of hydrophilic drugs can be achieved by dissolving them in the buffer used for rehydration of the dried lipid film. However, the method shows poor entrapment efficiency(20–30%) and larger amounts of drug will remain in the buffer

Question 5

how can you indirectly encapsulate hydrophilic drugs?

Answer 5

Therefore:
- permeability of bilayer membranes of empty liposomes is increased and the drug diffuses via the bilayer into the inner cavity.
- Use of dehydration (lyophilisation)/rehydration
cycles to increase permeability leads to fairly MLVs.

Question 6

how can entrapment of doxorubicin via indirect encapsulation be achieved?

Answer 6

two ways
method 1: liposome with same ph of buffer and drug sub + OH and +H
method 2: LIPOSOME pushing out NH3 and doxorubicin-NH2 coming in

Question 7

why is storage stability an issue with liposomes?

Answer 7

If liposomes are suspended in an aqueous
solution, the stability of liposomal products with hydrophilic drugs is low, because the drug will gradually diffuse from the inner cavity through the bilayer into the outer phase.

Question 8

what precautions are taken to reduce instability in liposomes?

Answer 8

Due to use of lipids: liposomal preparations are subjected to oxidation antioxidant (e.g. 0.1% a–tocopherol) is used.
Hydrolysis of the ester bonds of lipids can take place minimised at pH=6.5

Question 9

what happens on storage of liposomes?

Answer 9

On storage, small liposomes will fuse to form larger, thermodynamically more stable vesicles. Hence, products containing SUVs and LUVs are freeze-dried to be reconstituted before the administration (this is possible for parenteral formulations but not for topical applications)

Question 10

when is the reconstitution process not suitable?

Answer 10

is not suitable to products containing hydrophilic drugs, because the liposomal bilayers are temporarily porous during the process permitting the drug to diffuse out of the vesicle into the reconstitution medium.

Question 11

what are some interrelated factors influencing the physio-chemical properties of niosomes?

Answer 11

hydration temperature
➢nature of the drug
➢choice of the main surfactant
➢nature of the membrane additives (co-surfactant
and fluidity modulating agent)

Question 12

what happens at temperatures above the phase transition?

Answer 12

niosomes do not form spontaneously

Question 13

what are some areas of potential use for niosomes?

Answer 13

Parental
➢pulmonary
➢oral for the delivery of peptides
➢in ophthalmic preparations

Question 14

what are the benefits of using liposomes/niosomes to encapsulate drugs?

Answer 14

Solubilisation of drugs
(If the drug is lipid soluble it can be incorporated into the lipid part of the vesicle, e.g. minoxidil and amphoteracin B)
➢Drug release can be modified
(e.g. delay of drug release and alteration of drug permeability via biological membranes)
➢Site avoidance (The uptake of vesicles such as liposomes and niosomes into heart, kidneys, brain and the gut wall is minimal and thus dose-limited side effects and toxicity are usually reduced compared with free drug)
➢Site-directed targeting
(If charged molecules are incorporated, leading to anionic or cationic liposomes, or if, groups such as antibodies are attached site-targeted drug delivery can be achieved)
➢Clearance by RES
(useful for treatment of RES diseases)

Question 15

give an example of pharmaceutical application of liposomes

Answer 15

retinoids- in the treatment of acne

Question 16

what does effectivity of minoxidil depend on?

Answer 16

depends on the size of vesicles
smaller vesicles= more drug substance molecules

Question 17

how does it passivel target liver and spleen to improve efficacy and to reduce toxicity?

Answer 17

treatment of systemic fungal infections with Amphotericin B (polyene antibiotic) is associated with renal toxicity
➢liposomal Amphotericin B (Ambisome®) targetsliver and spleen passively whereby reducing renaland general toxicity at normal doses
➢was first liposomal preparation licensed for clinical use

Question 18

how does it actively target lungs?

Answer 18

➢Coating of vesicles with polyethylene oxide
➢Encapsulation of anti-tuberculosis drugs such as rifampicin or isoniazid reduces their toxicity and improves their efficacy

Question 19

define pro-liposomes

Answer 19

are dry free flowing solid drug
products with a dispersed system that can form a liposomal suspension in contact with an aqueous phase.

Question 20

what do pro-liposomes need?

Answer 20

usually they need carrier systems such as sodium chloride or sugar such as trehalose, sorbitol, mannitol.

Question 21

what are the advantages of pro-liposomes?

Answer 21

Pro-liposomes are effective formulations to solve problems associated with liposomes:
Aggregation
Sedimentation
Fusion
Hydrolysis and oxidation
Drug leakage
Also, pro-liposomes could improve the oral
delivery of the drugs due to their abilities to
retain their integrity at the absorption site

Question 22

why is advantageous for pro-liposomes to be dry free flowing powders?

Answer 22

stable phospholipid formulations
scale-up production
prolonged shelf-lives

Question 23

what is the importance of pro-liposomes as drug delivery systems?

Answer 23

Drug targeting
➢Drug solubilisation
➢Drug protection
➢Controlled release properties
➢Cationic - DNA complex for gene delivery into
cells

Question 24

how do you manufacture pro-liposomes?

Answer 24

1 Particulate based pro-liposome
Sugar particles (300-500mm), phospholipid, cholesterol the drug All in chloroform>
Evaporation of solvent, rotary evaporator>
Dry powder

2 Alcohol based pro-liposomes
Phospholipid, cholesterol, the drug dissolve in 95% ethanol > ethanolic lipid solution containing the drug >
Sugar such as sucrose or mannitol is then suspended in the solution >
Evaporation of ethanol: spray drying can be used >
Dry pro-liposome powder

Question 25

what are the characterisation methods for pro-liposomes?

Answer 25

Morphological properties
Particle size and particle charge characteristics
before and after reconstitution
flow properties
Drug content uniformity
Encapsulation efficiency
Thermal analysis
Cytotoxicity to specific cells
In-vitro drug release

Question 26

what are the possible routes of drug admin for pro-liposomes?

Answer 26

parenteral
pulmonary
oral
transdermal

Question 27

what are some advanced liposomal formulations?

Answer 27

Non conventional liposomal formulations
PEGylated (long circulating) liposomes
Immunoliposmes based cancer
therapeutics
PEGylated Immunoliposmes with cytotoxic
drugs

Question 28

what are the properties of ph sensitive liposomes?

Answer 28

phase transition in
alkaline media lead to increasing membrane fluidity
and release of encapsulated materials

Question 29

what are the properties of heat sensitive and ion sensitive liposomes?

Answer 29

They leak more readily at
temperatures above the phase transition temperature. They are formulated to be stable at normal body temperature, 37°C, and they release the drug upon hyperthermia (inside the tumour). They can enhance the delivery of cytotoxic drugs to the inside of tumours. Example: Prolieve®

Question 30

what are PEGylated liposomes?

Answer 30

“PEGylated liposomes”: the surface of vesicles is modified with hydrophilic polymers, which will reduce the agglomeration tendency of the vesicles
and will avoid recognition and removal of the vesicles by the RES. The polymer (PEG) is conjugated to the terminal amine groups
(phosphatidylethanolamine).

Question 31

what is PEGylated liposomes associated with?

Answer 31

PEG is strongly associated with water
molecules (hydration), it provides a hydrated surface layer around the liposomes, no detection of the vesicles by macrophages and the RES.

Question 32

what size PEGylayed liposomes can target solid tumours passively?

Answer 32

100nm

Question 33

how do PEGylayed liposomes maintain stability?

Answer 33

In vivo stability of liposomes is important
for targeted liposomes: they should maintain stability in the plasma till release of contents at the target site.

Question 34

what are immunoliposomes?

Answer 34

Immunoliposomes are antibody conjugated liposomes.
Liposomes can carry drugs or therapeutic nucleotides and when they conjugated with monoclonal antibodies (mAb): the entrapped drug(s) will release into targeted cells.

Question 35

why are immuniliposomes beneficial?

Answer 35

Beneficial than liposomes due to retention of immunoliposomes (via the mAb)to tumour through stable linkages

Question 36

how do immunoliposomes work?

Answer 36

Liposome acts as a drug carrier
The antibody allows bringing the drug system specifically to its target.
Tumour cells have molecules for recognition but also they have common characteristics with normal cells.
Accordingly, it is essential to find a suitable target for effective immunoliposomalformulations.
Tumor-overexpressed proteins …TARGET

Question 37

what about negatively charged liposomes?

Answer 37

more rapidly removed from circulation than neutral or positively charged liposomes: lipid composition (phosphatidylserine, phosphatidic acid, and phosphatidylglycerol versus sterically shielded phosphatidylinositol).

Question 38

what can liposomal uptake be reduced by?

Answer 38

stericallystabilised additives “Steric stabilisation” means the colloidal stability resulting from addition of hydrophilic polymers or glycolipids into liposomes.

Question 39

what do sterically stabilised liposome show?

Answer 39

prolonged stay in the circulation as compared with non-stabilised liposomes and also they are less reactive toward serum proteins and less susceptible to RES uptake