INTRODUCTION:
New drug delivery systems (NDDS)
are innovative technologies and new formulations that have attracted
considerable interest, particularly in the treatment of cancer and diseases
related to immunodeficiency, due to their high efficiency. The drug delivery system
enhances the effectiveness of the drug, controls the release rate, improves
safety and precisely delivers the drug
to the target tissue. Additionally, over longer periods of time, this
method maintains therapeutic concentrations within the therapeutic range. [1][
2]
The NDDS applications seek to
build a carrier system that can carry the molecules reliably and deliver them
to the correct designation without damaging normal physiological processes. By
binding the drug to a carrier particle like liposomes, niosomes, microspheres,
etc., which modulates the absorption characteristics of the drug and bypasses
the restriction of oral delivery, an appropriate carrier, which protects the
drugs from rapid degradation or clearance, enhances drug concentration in
target tissue. Liposomes and niosomes are 2 different well-researched drug
delivery vans. Niosomes are a promising drug delivery system because of their
biodegradable, biocompatible, and non-immunogenic structure. [3][5]
Niosomes are a novel drug
delivery system that incorporates the drug in a vesicle. Niosomes are spherical
and comprised of microscopic lamellar structure. It is composed of a bilayer of
nonionic surfactants and cholesterol. And since niosomes are amphiphilic in
nature, hydrophilic drugs can be microencapsulated in the core cavity and
hydrophobic drugs in the non-polar region present within the bilayer, and hence
both hydrophilic and hydrophobic drugs can be used in niosomes. Niosomes have
been shown to significantly improve transdermal drug delivery and can also be
used in targeted drug delivery. [6]
Importance:
The chief goal of the research
was to design and implement Niosomal gel in order to enhance bioavailability,
reduce dosing frequency, and improve patient compliance by overcoming the risks
of oral administration. The niosomal formulation increases the drug's water
solubility. The drug has been released in a controlled manner by a vesicles of
the niosomes. The topical route was chosen for this work because topical drug
delivery systems have been used for centuries to treat pain and inflammation.
On the one hand, topical drug application offers the potential benefits of
delivering the drug directly to the site of action and for an extended period
of time at the effected site and the drug. Drugs with the highest Log P, Pka
value, and bioavailability due to high first pass metabolism and short
half-life that is suitable of transdermal drug delivery system. [2]
What Is NIOSOME?
A niosome is a non-ionic
surfactant-based vesicle. Niosomes are formed mostly by non-ionic surfactant
and cholesterol incorporation as an excipient. [7]
Niosomes are microscopic
structures with lamellar structures. They are made up of a non-ionic surfactant
from the alkyl or dialkyl polyglycerol ether class and cholesterol, later on
hydrated in aqueous media. The surfactant molecules tend to orient themselves
so that the non-ionic surfactant's hydrophilic ends point outwards as well as
the hydrophobic ends face each other to form the bilayer. [8]
Figure 1:- Structure of Niosome
Various Types Of Niosomes:
Niosomes are classified into
three groups based on vesicle size.
Small unilamellar vesicles (SUV,
size=0.025-0.05 m),
Multilamellar vesicles (MLV,
size=0.05 m), and
Large unilamellar vesicles (LUV,
size=0.10 m) are the three types.[8]
Advantages of Niosomes: [8]
·
Because the vesicle suspension is
water-based, it provides better patient compliance than oil-based systems.
·
Because the structure of the
niosome allows for the incorporation of hydrophilic, lipophilic, and ampiphilic
drug moieties, they can be used for a wide range of drugs.
·
The vesicle's characteristics,
such as size, lamellarity, and so on, can be changed depending on the
situation.
1. The vesicles can act as a depot, allowing the drug to be
released slowly and in a controlled manner.
2. They are stable and osmotically active.
3. They improve the entrapped drug's stability.
4. Surfactant handling and storage do not necessitate any special
conditions.
5. Drugs' oral bioavailability can be increased.
6. Can improve drug penetration through the skin.
7. They can be taken orally, parenterally, or topically.
8. The surfactants are compostable, non-immunogenic, and
biocompatible.
·
Improve the drug's therapeutic
performance by shielding it from the biological environment and restricting
effects to target cells, reducing drug clearance.
·
To control the release speed of
the medication and administer normal vesicles in an external non-aqueous phase,
niosomal dispersions in an aqueous phase can be homogenised in a non-aqueous
phase.
Disadvantages of Niosome :
At the identical time, niosomes
get some drawbacks that may reduce their shelf life. These drawbacks include
both chemical and physical instability, agglomeration, vesicle fusion, and
leakage or hydrolysis of a entrapped drug. Furthermore, the methods required
for the production of multilamellar vesicles, like as extrusion and sonication,
are time-consuming or might necessitate the use of specialised equipment.[9]
Compositions of Niosomes:
The two primary elements used to
prepare niosomes are,
1. Cholesterol
2. Nonionic surfactants
1. Cholesterol-:
Cholesterol is indeed a steroid
product that is used to give niosome preparations rigidity or proper shape and
conformation.
2. Nonionic surfactants-:
Non-ionic surfactants such as the
ones listed below are commonly utilized during the process of making niosomes.
1. Spans (span 60, 40, 20, 85,
80)
2. Tweens (tween 20, 40, 60, 80)
3. Brijs (brij 30, 35, 52, 58,
72, 76)
The hydrophilic head and
hydrophobic tail of nonionic surfactants.[10]
Method of Preparation of Niosomes:
Niosomes can be developed in an array of ways, including the
following:
1. Ether Injection Method:
In this method, the surfactant is dissolved in diethyl ether to
form a solution. This solution is then injected (14 gauge syringe) in to the
warm water and aqueous phase containing the drug that is kept at 60°C. Ether
vaporisation results in the formation of single-layered vesicles. The size of
the particles of the formed niosomes depends on the circumstances used and can
range from 50 to 1000µm [11]
2. Hand Shaking Method (Thin Film
Hydration Technique):
In this method,
a round bottom flask is filled with a mixture of vesicle forming agents like
surfactant and cholesterol solubilized in an organic volatile solvent like
diethyl ether or chloroform. A rotary evaporator is used to remove the organic
solvent at room temperature, leaving a thin film of mixture coated on the flask
walls. This dehydrated surfactant film is then gently rehydrated with aqueous
phase to produce multilamellar niosomes. The resulting multilamellar vesicles
can then be processed to produce unilamellar niosomes and smaller niosomes via
sonication, microfluidization, or membrane extrusion techniques.[11]
3. Reverse Phase Evaporation
Technique:
This method
involves preparing a remedy of cholesterol & surfactant (1:1) in ether and
chloroform. After adding an aqueous phase that includes the drug be loaded, the
two phases have been sonicated at 4-5°C. And after addition of saline phosphate
buffered with phosphate, a clear gel is produced and sonicated (PBS). The
temperature is then raised to 40°C, and the pressure decreases to eliminate the
organic phase. This produces a viscous niosome mixture that can then be diluted
to PBS and heated for 10 minutes in a bath of water at 60°C to yield niosomes.[12]
4. Trans Membrane pH Gradient
(inside acidic):
Drug Uptake
Method (Remote Loading): For this method, a chloroform solution of surfactant
as well as cholesterol is prepared. Parallel to a hand shaking method, the
solvent is again rotary evaporator to produce a thin film upon this wall inside
the round bottom flask. This film then is vortexed hydrated with a solution of
citric acid (300mM, pH 4.0). The generated multilamellar vesicles then are
sonicated after three freeze-thaw cycles. Aqueous solution was prepared by
dissolving 10mg/ml of active substance is introduced to the niosomal dispersion
and vortexed. After that, 1M disodium phosphate is used to raise the pH of the
sample to 7.0-7.2. (this causes the drug which is outside the vesicle to become
non-ionic and can then cross the niosomal membrane, and once inside it is again
ionised thus not allowing it to exit the vesicle). The mixture is then heated
for 10 minutes at 60°C to produce niosomes.[13[
5. The “Bubble” Method:
It is a
relatively new technique that allows for the manufacturing of niosomes using no
organic solvents. The bubbling unit is made up the round bottom flask of three
necks that is placed in one water bath to regulate the temperature. The first
and second necks contain a water-cooled reflux and thermometer, while the third
neck is being used to supply nitrogen. At 70°C, cholesterol & surfactant
are dispersed in an equal amount of buffer (pH 7.4). This dispersion is blended
for 15 seconds with a high shear homogenizer before being bubbled at 70°C with
nitrogen gas to produce niosomes.[14]
6. Formation of Proniosomes And
Niosomes From Proniosomes:
To make proniosomes, a water-soluble carrier like sorbitol is
encapsulated with the surfactant first. To coat the sorbitol powder, a solution
of a surfactant and cholesterol in an organic solvent is prepared and sprayed
over onto powder in the rotary evaporator. The evaporation of a organic phase
produces a thin layer on sorbitol particles. The resulting layer is a dry
formulation consisting of the water soluble particle coated with a thin layer
of dry surfactant. Proniosome is the name given to this preparation. The
niosomes can be produced from the proniosomes through briefly agitating the
proniosomes with the aqueous phase containing the drug at a temperature higher
than the surfactant's mean transition phase temperature.[15]
7. Sonication:
The drug in the
aqueous phase is mixed with the surfactant & cholesterol inside a
scintillation vial. For 3 minutes, a sonic probe is used to homogenise the
mixture at 60°C. Small as well as uniform in size, the vesicles.[16]
8. Micro Fluidisation:
Within the
interaction chamber, two fluidised streams move ahead through a definite micro
channel & interact at ultra-high velocities. A prevalent gateway is used
here to ensure that an energy supplied to a system stays inside the area of noisome
formation. As a result, there is greater uniformity, smaller size, and improved
reproducibility.[17]
9. Multiple Membrane Extrusion
Method:
Evaporation is
used to create a thin film from a combination of surfactant, cholesterol, &
diacetyl phosphate in chloroform. The film is kept moist with aqueous drug
solution, and the resulting suspension is extruded through a series of
polycarbonate membranes for a maximum of eight passages. This is an effective
method for regulating niosome size.[18]
10. Niosome Preparation Using
Polyoxyethylene Alkyl Ether:
An alternative
method is available to change the number and size of polyoxyethylene alkyl
ether as well as cholesterol bilayer vesicles.[19]
11. Emulsion Method:
An organic
mixture of surfactant, cholesterol, as well as an aqueous solution of a drug
are combined to make a oil in water (o/w) emulsion. After that, the organic
solvent is evaporated, leaving the niosomes diffused in the aqueous phase.[20][21]
12. Heating Method:
It's a patented method that was built by Mozafari et al.
Surfactants & cholesterol are hydrated separately in buffer before solution
is brought up to 120°C to stirring to solubilize the cholesterol. While
stirring, its temperature is decreased and surfactants or other additives are
added to the buffer wherein cholesterol is dissolved. Niosomes are formed at
this stage, then left at room temp before being stored at 4-5°C in a nitrogen
atmosphere tight container.[22]
APPLICATIONS:
Niosomal formulations are a novel
drug delivery technique with such a variety of applications, including:
·
gene transfer.[23][24][25]
·
drug pinpointing.
·
antineoplastic therapy.
·
leishmaniasis treatment.
·
Peptide drug delivery.
·
Research immune response.
·
carriers for haemoglobin.
·
transdermal drug administration
systems.
·
cosmetics and cosmeceuticals.
CONCLUSION:
The NDDS approaches seek to
formulate a carrier system that can effectively hold the molecule and then
navigate it to the correct designation without altering the body's
physiological conditions. The basic component of drug delivery systems is an
adequate carrier that aims to protect drugs from metabolic degradation or
clearance and thus increases drug concentration in targeted site by attaching
the drug to the carrier particle like liposomes, niosomes, microspheres, and so
on, which mediates the absorption properties of the drug while overcoming the
disadvantages of oral delivery. Liposomes and niosomes seem to be two
well-studied drug delivery carriers. Niosomes are a promising drug carrier due
to their biodegradable, biocompatible, and non-immunogenic structure.
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