Drug targeting is the ability of a curative agent to move on coveted site of action with small or no interaction with non mark tissue. Niosomes are one of the best bearers for drug targeting. Niosomes are Microscopic lamellar construction formed on alloy of non ionic wetting agent of the alkyl or dialkyl polyglycerol ether category and cholesterin with subsequent hydration in aqueous media. Niosomes can be SUV ( Small Unilamellar Vesicles ) , MLV ( Multi lameller Vesicles ) or LUV ( Large Unilamellar Vesicles ) . The method of readying of noisome is based on liposome engineering. The basic procedure of readying is same like hydration by aqueous stage of the lipid stage which may be either a pure wetting agent or mixture of wetting agent or mixture of wetting agent with cholesterin. Niosomes are of import vehicle for drug bringing and being nonionized which is less toxic and better the curative index of drug by curtailing action to aim cells. Niosomes have shown good release profile and therefore function better option for drug bringing system.
Niosome, Mutilamellar cyst,
Target oriented drug bringing system are the countries of major involvement in the modern pharmaceutical research. The selective drug bringing to the mark tissue increases the curative efficiency of the drug and decreases its unwanted consequence of non mark tissue. Niosomes are microscopic lamellar construction, one type of nonionized surfactant cyst, alloy of nonionized wetting agent of alkyl or dialkyl polyglycerol ether category and cholesterin with subsequent hydration in aqueous media. [ 1.14.2 ] The presence of the steroidal system ( cholesterin ) increase the Rigidity of the bilayer and of import constituent of the cell membrane and its presence affects bilayer fluidness and permeableness. This bearer system protect the drug molecule from the premature debasement and inactivation due to unwanted immunological and pharmacological effects. [ 1.4.4 ] . Niosomes and liposomes are equiactive in drug bringing potency and both increase drug efficiency as compared with that of free drug. Mostly niosomes are preferred over liposome because the former exhibit high chemical stableness and economy. [ 1.21.4 ] . This article fundamentally stress on the increasing involvement of assorted discoverer and research workers in nano size colloidal systems, specially foregrounding the niosomal drug bringing system.
Advantages: ( 4,5 ) [ 1.11.3-4 ]
Niosomal scattering in an aqueous stage can be emulsified in a non-aqueous stage to modulate the bringing rate of drug and administer normal cyst in external non aqueous stage.
Niosomes possess an substructure consisting of hydrophilic, amphiphilic and lipotropic medieties together and as a consequence can suit drug molecule with a broad scope of solubilities.
They improve unwritten bioavalability of ailing absorbed drugs and enhance skin incursion of niosomes.
They increase the curative public presentation of the drug molecule by delayed clearance from the circulation, protecting the drug from biological environment and curtailing effects to aim cells.
The wetting agent are biodegradable, biocompatible and non-immunogenic hence can be used safely in readying of niosomes.
The cyst may move as a terminal, let go ofing the drug in a controlled mode.
They are osmotically active and stable, every bit good as they increase the stableness of entrapped drug.
They can be made to make the site of action by unwritten, parenteral every bit good as topical paths.
Disadvantages: [ 1.6.13 ] ( 6 )
Such type of drug bringing system holding high cost.
It has low solubilty and low stableness.
Escape and Fusion of encapsulated drug or molecules is seen.
It has short half life.
Sometimes phospholipid undergoes oxidization and hydrolysis.
Components OF NIOSOMES:
Chiefly niosomes contains following types of constituents.
Non Ionic wetting agents:
It holding bilayer lattices in which the hydrophillic caputs align confronting aqueous majority while the hydrophobic caput holding less contact with aqueous media. [ 1.4.4 ]
Following types of Nonionized wetting agents are
Surfactant-I ( MW-473 ) is C16 monoalkyl glycerin quintessence with norm of three glycerin units.
Surfactant-II ( MW-972 ) is diglycerol ether with norm of the seven glycerin units.
Surfactant-III ( MW-393 ) is ester linked wetting agent other than alkyl glycerin, alkyl glycosides & A ; alkyl ether bearing polyhydrixyl caput group are besides used in preparation of niosomes. [ 1.4.4-6-7 ]
Alkyl Esters: In this class Sorbitan esters are largely preferable wetting agent for readying of niosomes. [ 1.4.8-9 ] . Vesicles which are prepared by the polyoxyethelyne sorbitan glandular fever laurate are comparatively soluble than other surfactant cysts. [ 1.4.10 ]
For e.g. Polyoxyethylene ( polysorbate 60 ) has been utilized for encapsulation of Diclofenac Na. A mixture of polyoxyethelene-10-steryl quintessence: glyceryl laurate: cholesterin ( 27:15:57 ) has been used in Transdernal bringing of cyclosporine-A. [ 1.4.4, 12 ]
Alkyl Amide: Galactoside and Glucoside have been utilized to bring forth niosomal cyst [ 1.4.13 ]
Fatty acid and Amino acid Compounds: some long concatenation fatty acid and amino acid compounds have been utilized in some niosomal readying. [ 1.4.14 ]
Steroids are of import constituents of the cell membrane and their presence in membrane affect the bilayer fluidness and permeability.Cholesterol which is a steroid derived function and used in preparation of niosomes but may non demo any function in the formation of bilayer.
Here cholesterin affect belongingss of niosomes like membrane permeableness, Rigidity, encapsulation efficiency, easiness of rehydration of freezing dried nauseating and their toxicity. It prevent the cyst collection by the inclusion of molecules which stabilize the system against the formation of sums by abhorrent steric or electroststic forces that leads to the passage from the gel to liquid stage in nauseating system. Hence the nauseating becomes leaky. [ 1.4.15 ]
To Increase the stableness of nauseating by electrostatic repulsive force which prevents coalescency, some charged molecule are added to niosomes.
The negatively charged molecules [ e.g. Diacetyl phosphate ( DCP ) and Phosphotidic acid. ] and
The positively charged molecules [ Stearylamine ( STR ) and staryl pyrimidium chloride ] are usage in niosomal readying. These charged molecules are used to forestall collection of niosomes [ 1.4.1,16 ] . But 2.5 to 5 mol % concentration of charged molecules are tolerable because high concentration inhibit niosome formation. [ 1.4.1,17 ] .
METHODS OF PREPARATION:
Hand Shaking Method ( Thin Film Hydration Technique ) [ 1.7.11 ] ( 16 )
The mixture of cyst organizing ingredients like wetting agent and cholesterin are dissolved in volatile organic dissolvers like diethyl quintessence, trichloromethane or methyl alcohol in a Round underside flask. The organic dissolver is evaporated at room temperature ( 20A°C ) utilizing rotoary evaporator go forthing a thin bed of solid mixture on the wall of flask. The dried movie can be rehydrated by aqueous stage at 0 to 60A°C with soft agitation, which will organize typical mutilamellar noisome.
Fig.1 Hand Shaking Method
Ether Injection Method: [ 1.6.22 ] ( 17 )
In this method niosomes are formed by presenting a solution of surfactant dissolved in diethyl quintessence into warm H2O maintained at 60A°C. The surfactant mixture in quintessence is injected through 14- gage niddle into an aqueous solution of stuff. Then ether will be vaporized leads to formation of individual layered cyst which has diameter from 50 to 1000 nanometer.
Sonication: ( 18 ) [ 1.6.23 ]
In this method an aliquot of drug solution in buffered is added to the wetting agent or cholesterin mixture in a 10 milliliter glass phial. The mixture is probe sonicated at 60A°C for 3 min. utilizing a sonicator with a Ti investigation to give niosomes.
Rearward Phase Evaporation Techniques: [ 1.6.23 ] ( 18 )
In this method, wetting agent and cholesterin are dissolved in a mixture of trichloromethane and quintessence.
An aqueous stage incorporating drug is added to this mixture and ensuing two stage is sonicated at 4-5A°C. The clear gel is formed which is further sonicated after the add-on of a little sum of phosphate buffer saline. The organic stage is removed at 40A°C under low force per unit area. Then ensuing syrupy nauseating suspension is diluted with phosphate buffered saline and heated in a H2O bath at 60A°C for 10 min to give niosomes.
Bulge method: [ 1.4.23,24 ] ( 19,20 )
In this method, the mixture of cholesterin and diacetyl phosphate is prepared and so dissolver is evaporated with the aid of rotary vaccum evaporator to go forth a thin movie. The movie is hydrated by aqueous drug solution and suspension therefore obtained is extruded through the polycarbonate membrane holding pore size 0.1 Aµm and so placed in series up to 8 transitions to obtain unvarying size niosomes.
Trans membrane pH gradient Drug consumption procedure ( Remote lading ) :
In this method cholesterin and wetting agent are dissolved in trichloromethane. The wetting agent is evaporated under decreased force per unit area to acquire obtain thin movie on the wall of unit of ammunition underside flask. The movie is so hydrated with 300 millimeters citric acid ( pH 4.0 ) by whirl commixture. The multilamellar cyst are frozen and thawed 3 times and so sonicated. To this niosomal suspension, aqueous solution incorporating 10 mg/ml of drug is added and vortexed. The pH of the sample is so raised to 7.0-7.2 with 1M disintegration phosphate. The mixture is so heated at 60°C for 10 min to give niosomes.
Multiple Membrane Extrusion method: [ 1.17.13 ] ( 22 )
For commanding the size of niosome, this one is good method. In this method wetting agent, cholesterin and diacetyl phosphate all are mixed in trichloromethane and signifier thin movie by Evaporation. The movie is so hydrated with aqueous drug solution and attendant suspension extruded through polycarbonate membranes which are placed in series for upto 8 transition.
Emulsion method: [ 1.14.26,27 ] ( 23,24 )
In this method the oil in H2O ( o/w ) emulsion is placed from an organic solution of wetting agent, cholesterin and an aqueous solution of drug. Then the organic dissolver is evaporated which go forthing a thin movie dispersed in aqueous stage.
Niosome readying utilizing Micelle:
Niosomes are formed from a assorted micellar solution by the usage of Enzymes. A assorted micellar solution of C16G2, dicalcium H phosphate, polyoxyethylene sholesterol sebacetate diester ( PCSD ) converts to a niosome scattering when incubated with esterase. PCSD is cleaved by esterase to give polyoxyethylene, sebacic acid and cholesterin. Cholesterol in combination with C16G2 and DCP so yield C16G2 niosomes.
Active Trapping Method: [ 1.3 ] ( 25 )
In this method burden of drug after the formation of niosomes. The niosomes are prepared and so drug is loaded by keeping pH gradient or ion gradient to ease consumption of drug into niosomes.
It has different advantage like 100 % entrapment, Absence of escape, High drug lipoids ratio, Cost effectual and suitableness for labile drug.
The Bubble Method: [ 1.3 ] ( 26 )
In this method niosomes are formed in one measure without usage of organic dissolver. All constituents are dispersed in buffer and the scattering is placed in a unit of ammunition underside flask which is immersed in H2O bath with controlled temperature. The flask has three cervixs attached to H2O cooled reflux, thermometer and nitrogen supply. The scattering is assorted with a shear homogenizer for 15 seconds and so bubbled with N in this assembly to organize niosomes.
Microfluidization: [ 1.3 ] ( 27 )
In this method the two stage are allowed to interact at extremist high velocity in micro channels in an interaction chamber. The high velocity encroachment and the enegy involved in this which leads to formation of uniformed little niosomes.
TYPES OF NIOSOMES:
The niosomes are calssified as map of the figure of Bilayer ( e.g. SUV, MUV ) or as a map of size ( e.g. LUV, SUV ) or as a map of the method of readying ( e.g. REV, DRV ) There are chiefly three types of niosomes [ 1.23.9 ]
Multi lamellar cysts ( MLV )
Large unilamellar cysts ( LUV )
Small unilammellar cysts ( SUV )
I. Multi lamellar Vesicles ( MLV ) :
It consists of a figure of bilayer environing the aqueous lipid compartment individually. The approximative size of such cysts are 0.5 to 10 Aµm diameter. MLV are most widely used niosomes. Which are simple to do and automatically stable upon storage for long periods. These cyst are largely suited as drug bearer for Lipophillic compounds
II. Large Unilamellar Vesicles ( LUV ) :
Such types of Niosomes are high aqueous to lipid compartment ratio, so that big volume of Bio-active stuffs can be entrapped with a really economical usage of membrane lipoids.
III. Small Unilamellar Vesicles ( SUV ) :
such types of niosomes are largely prepared from multi lamellar cysts by sonication method, Gallic imperativeness bulge method or Homonization method. The size of little unilamellar cysts are 0.025-0.05 Aµm diameter which are thermodynamically unstable and are susceptible to collection and merger. Their entrapped volume is little and per centum entrapment of a aqueous solute is correspondingly low.
Word picture OF NIOSOMES:
Entrapment efficiency: [ 1.17.23 ] ( 14 )
After fixing niosomal scattering, unentrapped drug is separated by Dialysis, Gel filteration or Centrifugation and the drug remained entrapped in noisome is determined by complete cyst break utilizing 50 % n-propanol or 0.1 % Triton X-100 and analysing the attendant solution by appropriate checks method for the drug.
Entrapped efficiency ( EE ) = Amount entrapped entire sum A- 100
Niosomes are spherical and so their diameter can be determined by Light Microscopy, photon correlativity microscopy and freezing break negatron microscopy. Freeze dissolving [ 1.17.24 ] ( 15 ) is besides applicable for such measuring.
In-vitro release: [ 1.17.24 ] ( 15 )
A method of in-vitro release rate survey include the usage of dialysis tube. A dialysis pouch is washed and soaked in distilled H2O. The cyst suspension is pipette out into a bag made up of tube and sealed. The bag incorporating the cyst is placed in 200 milliliter of buffer solution in a 250 milliliter beaker with changeless shaking at 25A°C and 37A°C. at assorted clip interval s. The buffer is analyzed for the drug content by an appropriate check method.
Bilayer Rigidity and Homogeneity: [ 1.9.7,8,9 ]
The Rigidity of bilayer affects biodistribution and biodegradation of niosomes. In homogeneousness can happen both within niosome construction themselves and between niosomes in scattering and could be identified via. p-NMR, Differntial scanning calorimertry ( DSC ) and Fourier transform infra-red spectrometry ( FT-IR ) techniques. Now a twenty-four hours, fluorescence resonance energy transportation ( FRET ) are used to obtain deeper penetration about the form, size and construction of niosomes.
Vesicle charge can play of import function in the behaviour of niosomes in vivo and in vitro. Charged niosomes are more stable against collection and merger than uncharged cyst. In order to obtain an estimation of the surface potency, the zeta potency of single niosomes can be measured by Microelectrophoresis. Another attack is the usage of pH-sensitive fluorophores. Dynamic light dispersing have been used to mensurate the zeta potency used now a yearss.
The niosomal preparation were subjected to stableness by hive awaying at 4C, 25C and 37C in thermostatic over for the period of three months. After one month, drug content of all the preparations were checked by method discussed antecedently in entrapped efficiency parametric quantity.
Tissue Distribution or In vivo survey:
This survey is carried out by utilizing suited carnal theoretical accounts like albino rats ( 100-150 gram ) . Largely three groups are taken each group contain three animate beings ( entire 3*3=9 ) . The first group is treated as control, in which free niosome without drug are injected. To the 2nd group free drug is injected. The 3rd group is treated by lyophilised niosome. After giving the animate beings, different tissue like liver, lungs, lien, bosom and kidney are removed. After rinsing the tissue with phosphate buffer ( pH-7.4 ) the organ are homogenized and centrifuged. The supernant is used for the finding of drug content utilizing suited method. [ 1.4.46 ] The wetting agents with alkyl side concatenation length from C12-C18 are suited for readying of niosomes [ 1.24.8 ] ( 33 ) . Span series wetting agent holding HLB figure of between 4 and 8 can organize niosomal cyst. [ 1.24.9 ] ( 34 )
Factor impacting physicochemical belongingss of niosomes:
Nature of Wetting agents:
Types of wetting agents affect encapsulation efficiency, toxicity and stableness of niosomes. The wetting agent used in formation of niosome must hold hydrophilic caput and hydrophobic tail. Hydrophobic tail consist of one or two alkyl or perfluoroalkyl groups or in some instances a individual steroidal group [ 1.24.6 ] ( 31 ) The quintessence type wetting agents with individual concatenation alkyl as hydrophobic tail is more toxic than matching dialkyl ether concatenation. The ester type wetting agent are chemically less stable but less toxic than ether type wetting agent. [ 1.24.7 ] ( 32 ) .
Table 1: Differnent types of Non-ionic wetting agent
Type of Non-Ionic wetting agent
Steryl intoxicant, Cetyl intoxicant Cetosteryl intoxicant, oleyl intoxicant
Glyceryl laurate, Polysorbates, Spans
Brij, Lauryl glucoside, Octyl glucoside, Nanoxylol-9
Structure of Wetting agents:
The construction of surfactant affects the geometry of cyst, which is related to critical wadding parametric quantity. Critical wadding parametric quantity ( CPP ) can be defined by following equestion. [ 1.21.20 ] ( 35 )
CPP = V / lc A- a0
Where, v = hydrophobic group volume
lc = the crical hydrophobic length,
a0 = the country of hydrophilic caput group.
From the CPP value, type of miceller construction can be predicted.
If CPP & lt ; A? so formation of spherical micelles, If A? & lt ; CPP & lt ; 1 formation of bilayer micelles and If CPP & gt ; 1 formation of upside-down micelles.
Temperature of hydration:
Hydration temperature affect the form and size of the niosome. For ideal status it should be above the gel to liquid stage passage temperature of system. Temperature alteration of niosomal system affects assembly of wetting agent into cysts and induces vesicle form transmutation. [ 1.21.21 ]
Nature of Encapsulated drug:
The physicochemical belongingss of encapsulated drug affect charge and rigidness of the niosome bilayer. Here drug interacts with surfactant caput group and develops the charge which creates common repulsive force between surfactant bilayer and hence addition cyst size. [ 1.21.19 ] ( 37 ) The collection of cyst is prevented due to the charge which is developed on bilayer. In PEG ( polyoxyethylene ethanediol ) coated cyst, some drug is entrapped in the long PEG concatenation, therefore cut downing the inclination to increase the size. [ 1.24.15 ] ( 38 )
Table 2: Consequence of the Nature of Drugs on the formation of Niosomes
Nature of the Drugs
Escape from cyst
Improve transdermal bringing
Altered cataphoretic mobility, increase encapsulation belongings
Different additives are added along with surfactant and drug to organize stable niosomes. Niosomes holding figure of morphologies, permeableness and stableness belongingss which can be altered by adding different additives. For e.g. Polyhedral niosomes formed from C16G2, the form of these niosome remains unaffected by adding low sum of solulan C24 ( Cholesteryl poly-24-oxyethylene quintessence ) , which prevent collection due to development of steric hindrance. [ 1.21.22 ] ( 39 )
Applications: [ 1.4 ]
As a Carrier for drug bringing
I± , I‰-Hexadecyl-bis- ( 1-aza ) 18-crown-6 ( bolo tie ) ,
Span 80, Cholesterol
Thin bed vaporization method
5- flurouracil ( 5-FU )
For Brain aiming
N-Palmitoyl glucosamine ( NPG ) , Span 60, Cholesterol, Solulan C24
Probe sonication technique
Vasoactive enteric peptides
To Improve Bioavalability
Cholesterol, Span 60, Span 20, Span 40, Dicetylphosphate ( DCP )
Film hydration method
Span 40, Cholesterol, DCP
Solvent vaporization technique
To protract the release clip
Rearward stage vaporization method
Cholesterol, DCP and Tween 85 or pluronic F108
Rearward stage vaporization method