Niosomes by kalyan
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Niosomes by kalyan






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Niosomes by kalyan Niosomes by kalyan Presentation Transcript

    M.Pharmacy (Pharmaceutics) 2 ndsemester
    Methods of Preparation
    Factors Affecting NiosomesPreparation
    Stability of Niosomes
    Applications of Niosomes.
  • Introduction
    Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle composed of a bilayer of non-ionic surface active agents .
    These are very small, and microscopic in size that lies in the nanometric scale. Although structurally similar to liposomes, they offer several advantages over them.
    Niosomes have recently been shown to greatly increase transdermal drug delivery and also in targeted drug delivery.
  • WHY ? WHY? WHY?
    Used for a variety of drugs : accommodate hydrophilic, lipophilic as well as amphiphilic moieties.
    Act as a depot to release the drug slowly and offer a controlled release .
    Osmotically active and stable.
    Increase the stability of the entrapped drug.
    Handling and storage of surfactants do not require any special conditions
    Enhance the skin penetration of drugs
  • Structure of Niosomes
    Niosomes are microscopic lamellar structures, which are formed on the admixture of non-ionic surfactant of the alkyl or dialkylpolyglycerol ether class and cholesterol with subsequent hydration in aqueous media.
    Niosomes may be unilamellar or multilamellar depending on the method used to prepare them.
    The hydrophilic ends areexposed on the outside and inside of the vesicle, while the hydrophobic chains face each other ` within the bilayer.
    Hence, the vesicle holds hydrophilic drugs within the space enclosed in the vesicle, while hydrophobic drugs are embedded within the bilayer itself.
  • Contd…
  • Small
    Typical Size Ranges: SLV: 20-50 nm – MLV:100-1000 nm
  • Niosomes Vs Liposomes
    In both basic unit of assembly is Amphiphiles, but they phospholipids in liposomes and nonionic surfactants in niosomes.
    Both can entrap hydrophilic and lipophilic drugs.
    Both have same physical properties but differ in their chemical composition.
    Niosomes has higher chemical stability than liposomes.
    Niosomes made of uncharged single chain surfactant molecules
    Liposomesmade of neutral or charged double chain phospholipids.
  • Similarity : Niosomes & Liposomes
    • Function
    • Increase the bioavailability
    • Decrease the clearence
    • Used for targeted drug delivery
    • Properties depends on both composition of bilayer and method of preparation
  • Advantages : Niosomes Over Liposomes
    • Ester bonds of phospholipids are easily hydrolyzed, this can lead to phosphoryl migration at low PH.
    • Peroxidation of unsaturated phospholipids.
    • As liposomes have purified phospholipids they are to be stored and handled at inert(N2) atmospheres where as Niosomes are are made of non ionic surfactants and are easy to handle and store.
    • Phospholipid raw materials are naturally occurring substances and as such require extensive purification thus making them costly
  • Niosomes : Types
    1.Bola-Surfactant containing Niosomes:
    Niosomes made of alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio) are named as Bola-Surfactant containing Niosomes.
    2. Proniosomes:
    A dry product which may be hydrated immediately before use to yield aqueous Niosome dispersions. These ‘proniosomes’ minimize problems of Niosome physical stability such as aggregation, fusion and leaking, and provide additional convenience in transportation, distribution, storage, and dosing.
  • Formation of niosomes from proniosomes
  • Factors Affecting NiosomesFormation
    Hydration Temperature
    Non-ionic surfactant nature
    Factors affecting niosomes formation
    Surfactants and lipid levels
    Membrane additives
    Nature of encapsulated drug
  • Contd…
    Nature of non-ionic surfactant
    Type of surfactant influences encapsulation efficiency, toxicity, and stability of niosomes
    Linked via ether , amide or ester bonds
    Hydrophobic tail
    Hydrophilic head
    Consist of one or two alkyl or perfluroroalkyl groups or in some cases a single steriodal group.
  • Contd…
    • The alkyl group chain length is usually from C12-C18
    • Uchegbu et al reported that Span surfactants with HLB values between 4 and 8 were found to be compatible with vesicle formation
    • The water soluble detergent polysorbate 20 (HLB value 16.7) also forms niosomes with cholesterol
    • Polyglycerolmonoalkyl ethers and polyoxylate analogues are the most widely used single-chain surfactants
  • Contd…
    Membrane additives
    Cholesterol, a natural steriod, is the most commonly used membrane additive
    Usually incorporated in 1:1 molar ratio
    Prevent vesicle aggregation by the inclusion of molecules that stabilize the system against the formation of aggregates by repulsive steric or electrostatic effects
    Leads to the transition from the gel state to liquid phase in niosomes systems
    As the result, niosomes become less leaky
    Dicetyl phosphate provides negative charge to vesicles
    It is used to prevent aggregation of hexadecyldiglycerol ether (C16G2) niosomes
    Stearic acid is used in the preparation of cationic niosomes
    Dicetyl phosphate and Stearic acid
  • Contd…
    Surfactant and lipid levels
    The surfactant/lipid ratio is generally 10-30 mM (1-2.5% w/w)
    If the level of surfactant/lipid is too high, increasing the surfactant/lipid level increases the total amount of drug encapsulated
    Hydration temperature
    • The hydrating temperatures used to make niosomes should usually be above the gel to liquid phase transition temperature of the system
  • Methods Of Preparation
    • Ether injection method
    • Film method
    • Sonication
    • Reverse phase evaporation
    • The “Bubble” method
    • Micro fluidization.
  • Contd…
    Ether injection method
    • Slow injection of an ether solution of niosomal ingredients into an aqueous medium at high temperature
    • A mixture of surfactant and cholesterol (150 μmol) is dissolved in ether (20 ml) and injected into an aqueous phase (4 ml) using a 14- gauge needle syringe
    • Temperature of the system is maintained at 60oC during the process
    • Niosomes in the form of large unilamellar vesicles (LUV) are formed
  • Contd…
    Film method
    • The mixture of surfactant and cholesterol is dissolved in an organic solvent (e.g. diethyl ether, chloroform, etc.) in a round-bottomed flask
    • The organic solvent is removed by low pressure/vacuum at room temperature
    • The resultant dry surfactant film is hydrated by agitation at 50-60oC
    • Multilamellar vesicles (MLV) are formed
  • Contd…
    • The aqueous phase is added into the mixture of surfactant and cholesterol in a scintillation vial
    • Homogenized using a sonic probe
    • The resultant vesicles are of small unilamellar (SUV) type niosomes
    • The SUV type niosomes are larger than SUV liposomes
    • It is possible to obtain SUV niosomes by sonication of MLV type vesicles
  • Contd…
    Reverse phase evaporation
    • Surface-active agents are dissolved in chlorofom, and 0.25 volume of phosphate saline buffer (PBS) is emulsified to get w/o emulsion
    • The mixture is sonicated and subsequently chloroform is evaporated under reduced pressure
    • The surfactant first forms a gel and then hydrates to form niosomal vesicles
    • The vesicles formed are unilamellar and 0.5 μ in diameter
  • Contd…
    The “Bubble” method
    It is novel technique for the one step preparation of liposomes and niosomes without the use of organic solvents
    The bubbling unit consists of round-bottomed flask with three necks positioned in water bath to control the temperature
    Water-cooled reflux and thermometer are positioned in the first and second neck and nitrogen supply through the third neck
    Cholesterol and surfactant are dispersed together in the buffer (pH 7.4) at 70°C, the dispersion mixed for 15 secs with high shear homogenizer and immediately afterwards “bubbled” at 70°C using nitrogen gas
  • Contd…
    Micro fluidization
    This is a recent technique to prepare small MLVS
    A microfludizer is used to pump the fluid at a very high pressure (10,000 psi) through a 5 pm screen
    It is then forced along defined micro channels, which direct two streams of fluid to collide together at right angles, thereby affecting a very efficient transfer of energy
    The lipids/surfactants can be introduced into the fluidizer
    The fluid collected can be recycled until spherical vesicles are obtained
    Uniform and small sized vesicles are obtained
  • Contd…
    Post-Preparation Processes
    Separation of unentrapped material
  • Contd…
    Probe sonication
    Size reduction of niosomes
    Extrusion through filters
    High-pressure homogenization
    Combination of sonication and filtration
  • Dialysis
    Separation of unentrapped material from niosomes
    Gel filtration
  • Charecrisation of niosoms
    Entrapment efficiency
    • Depend on the method of preparation
    • Niosomes prepared by ether injection method have better entrapment efficiency than those prepared by the film or sonication
    • Addition of cholesterol to non-ionic surfactants with single- or dialkyl-chain significantly alters the entrapment efficiency
    • Surfactants of glycerol type lead to reduction in entrapment capacity as the amount of cholesterol increases
    • Niosomes in the form of liquid crystals possess better entrapment efficiency than gel type vesicles
  • contd…
    Entrapment efficiency (EF) = (Amount entrapped total amount) x100
    Niosomes, similar to liposomes, assume spherical shape and so their diameter can be determined using light microscopy, photon correlation microscopy and freeze fracture electron microscopy.
    Freeze thawing (keeping vesicles suspension at –20°C for 24 hrs and then heating to ambient temperature) of niosomes increases the vesicle diameter, which might be attributed to fusion of vesicles during the cycle.
  • contd…
    In-vitro release :
    A method of in-vitro release rate study includes the use of dialysis tubing. A dialysis sac is washed and soaked in distilled water. The vesicle suspension is pipetted into a bag made up of the tubing and sealed. The bag containing the vesicles is placed in 200 ml of buffer solution in a 250 ml beaker with constant shaking at 25°C or 37°C. At various time intervals, the buffer is analyzed for the drug content by an appropriate assay methodof vesicles during the cycle.
  • Stability Of Niosomes
    Vesicles are stabilised based upon formation of following forces:
    • van der Waals forces among surfactant molecules
    • Electrostatic repulsive forces are formed among vesicles upon addition of charged surfactants to the double layer, enhancing the stability of the system
  • Contd…
    Niosomes in the form of liquid crystal and gel can remain stable at both room temperature and 4oC for 2 months
    Recommended temperature of storage 4oC
    Ideally niosomes should be stored dry for reconstitution
    The factors which affect the stability of niosomes:
    • Type of surfactant
    • Nature of encapsulated drug
    • Storage temperature
    • Detergents
    • Use of membrane spanning lipids
    • Inclusion of charged molecule
  • Applications Of Niosomes
  • Contd…
    • Transdermal Applications
    • Slow penetration of drug through skin is the major drawback of transdermal route of delivery. An increase in the penetration rate has been achieved by transdermal delivery of drug incorporated in niosomes. has studied the topical delivery of erythromycin from various formulations including niosomes or hairless mouse.
    • parenteral Applications
    • Niosomes in sub-micron size are used for parenteral administration
    • Niosomal vesicles upto 10 μm are administered via i.p. or i.m.
  • Contd…
    • Radiopharmaceuticals
    • First application of niosomes as radiopharmaceuticals demonstrated by Erdogan et al. in 1996.
    • Delivery of peptide drugs
    Oral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped in niosomes increase stability of peptide significantly.
  • Contd…
    Ophthalmic Drug Delivery
    Saettone et al. (1996) reported on the biological evaluation of a niosomalCyclopentolate delivery system for opthalmic delivery
    Polysorbate 20 and cholesterol were used for niosomes formulation
    Optimum pH for peak permation values was pH 5.5, permeatiom decreased at pH 7.4
    But in vivo data showed no such dependent on pH
    Niosomes> 10 μm are suitable for drug administration to eye
  • Recent advances in niosomes
    •  Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.
    • Phase I and phase II studies were conducted for Niosomalmethotrexate gel in the treatment of localized psoriasis. These studies suggest that niosomalmethotrexate gel is more efficacious than placebo and marketed methotrexate gel.
    • A research article was published that Acyclovir entrapped niosomes were prepared by Hand shaking and Ether injection methods increases the oral bioavailability
    • Lancome has come out with a variety of anti-ageing products which are based on niosome formulations
  • Conclusion
    The concept of incorporating the drug into liposomes or niosomes for a better targeting of the drug at appropriate tissue destination is widely accepted by researchers and academicians.
    Niosomes represent a promising drug delivery module.
    Niosomes are thoughts to be better candidates drug delivery as compared to liposomes due to various factors like cost, stability etc .
    Various type of drug deliveries can be possible using niosomes like targeting, ophthalmic, topical, parenteral, etc.
     Niosomes can also serve better aid in diagnostic imaging and vaccine adjuvant in pharmaceutical industry.
  • References
    1. Malhotra M and Jain NK. Niosomes as Drug Carriers. Indian Drugs 31 (3), 1994, 81-86.
    2. Handjani-Vila RM., Ribier A, Rondot B and Vanlerberghie G. Dispersions of lamellar phases of non-ionic lipids in cosmetic products. International Journal of Cosmetic Science 1 (5), 1979, 303-314.
    3. Baillie AJ, Florence AT, Hume LR, Rogerson A, and Muirhead GT ,The preparation and properties of niosomes-non-ionic surfactant vesicles. J. PharmPharmacol. 37(12), 1985, 863–868.