IJCRT2405701
IJCRT2405701
IJCRT2405701
org © 2024 IJCRT | Volume 12, Issue 5 May 2024 | ISSN: 2320-2882
1
Shruti Satish Garad,2Chinni TejasGajanan, 3Choudhari Mohammad Sami Mohammad Toufhik,
4
Aniket Suresh Balgaonkar, 5Abhishek chavan
1
Assistant professor, Department of pharmaceutics, AFNIP Boramani, Solapur, Maharashtra, India
2345
Co-author Amepurva Forum’s Nirant Institute of Pharmacy, Solapur, Maharashtra, India
Abstract
Niosomes, which consist of vesicles formed by a combination of non-ionic surfactant and cholesterol, are a
subject of interest. These structures are capable of serving as carriers for drugs that possess both hydrophilic
and lipophilic properties. Within the realm of drug delivery systems, niosomes represent a method by which
pharmaceuticals can be enclosed within vesicles. The appealing characteristics of niosomes include their
biodegradability, biocompatibility, lack of immunogenicity, and structural flexibility. The primary aim of
this literature review is to shed light on the diverse therapeutic applications of niosomes in the treatment of
various medical conditions. This review will explore multiple facets concerning niosomes, such as their
preparation techniques, mechanisms of action, facilitation of drug permeation, utilization as permeation
enhancers, diverse applications in disease management, assessment of toxicity, and approaches to mitigating
toxicity through the utilization of surfactants.
INTRODUCTION:
The inception of targeted drug delivery can be traced back to the year 1909, when Paul Ehrlich initiated the
groundwork for delivering therapeutic agents directly to infected cells. The concept of drug targeting revolves
around the precise delivery of medication to specific sites within the body, thereby ensuring targeted action on
the intended tissues. Niosomes, a novel drug delivery system, involve the encapsulation of medication within a
polymer matrix in the form of vesicles. These vesicles, known as niosomes, consist of a dual layer of non-ionic
surfactants, with examples such as Span-60, typically stabilized through the addition of cholesterol and
significant amounts of anionic surfactants like dicetyl phosphate. The advantages of niosomes include the
efficacy of lower drug dosages, stability due to their hydrophilic nature resulting in osmotic activity, enhanced
drug stability through hydrophilicity, improved skin penetration of drugs, high patient acceptance due to the
hydrophilic nature of the vesicles, and their function as depots for slow drug release. However, niosomes also
present drawbacks such as the need for specialized equipment, high production costs, inefficient drug loading,
fusion, aggregation, leakage of entrapped drugs, and limitations in shelf life due to drug hydrolysis.
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Merits Of Niosomes
• A reduced dosage is sufficient to achieve the desired therapeutic effect.
• Niosomes exhibit stability due to their utilization of a hydrophilic system, which enhances osmotic activity.
• The hydrophilic nature of niosomes results in improved stability of the entrapped drugs. • Ability to facilitate
enhanced drug delivery through the skin.
• The hydrophilic vesicles in the suspension contribute to higher patient acceptance compared to oil-based
systems.
• Vesicles serve as reservoirs for gradual drug release.
Demerits of niosomes
• Potential need for specialized machinery.
• Elevated production expenses.
• Inadequate drug encapsulation efficiency.
• Issues such as fusion, aggregation, and leakage of entrapped drugs.
• The detrimental impact of hydrolysis on the enclosed drugs can restrict the shelf life of a specific formulation.
STRUCTURE OF NIOSOMES[1]
Niosomes, characterized by their amphiphilic nature, consist of a non-ionic surface-acting agent like Span-60,
which is stabilized by cholesterol and an ample amount of anionic surfactant such as dicetyl phosphate to
maintain the stability of the vesicles.
1. CHOLESTEROL:
Which is a steroid derivative employed to provide flexibility, rigidity, and appropriate shape.
PREPARATION OF NIOSOMES:
Sonication Method:
Various methods are employed for the preparation of niosomes. One such method involves adding the drug
solution into a buffer system, followed by the addition of this mixture into a surfactant or cholesterol mixture in
a 20ml glass vial. The combination is then sonicated at 60°C for 3 minutes using a sonicator with a titanium
probe to produce niosomes.
Hand shaking method (Thin film hydration techniques):
In this technique, surfactant and cholesterol are dissolved in a volatile organic solvent such as diethyl ether,
chloroform, or methanol in a round bottom flask. The organic solvent is evaporated at 20°C using a rotary
evaporator, leaving a thin layer of solid mixture on the flask surface. The dried film of surfactant can be
rehydrated with an aqueous phase at 0-60°C with gentle agitation to form multilamellarniosomes.
Micro fluidization method:
A modern approach to preparing unilamellar vesicles with a well-defined size distribution involves the use of
micro fluidization. This method relies on two fluidized streams at ultra-high velocities interacting with each
other. By directing the narrow liquid film onto a typical surface, the level of energy supplied to the system is
preserved at a suitable level for the creation of niosomes.The outcome is niosomes with enhanced uniformity,
smaller size, and improved reproducibility.
Reverse Phase Evaporation Technique (REV):
In the REV method, a 1:1 ratio of cholesterol and surfactant mixture is dissolved in organic solvents like
chloroform and ether. The drug is dissolved in the aqueous phase and added to the above mixture to form two
phases, which are then sonicated at 4-5°C. A clear gel is formed and further sonicated after the addition of
phosphate buffered saline. The organic phase is removed at 40°C under low pressure. The resulting niosomes
solution is viscous and is diluted with phosphate buffer, followed by heating in a water bath at 60°C to obtain
niosomes with high yield.
The Bubble Method:
This method involves the use of a foaming unit consisting of a round-bottom flask with three necks, placed in a
water bath for temperature control. Cholesterol and surfactant are dispersed in a buffer solution (pH 7.4) at
70°C, mixed for 15 seconds with a high shear homogenizer, and then bubbled at 70°C using nitrogen gas to
generate niosomes.
1. DRUGS
2. NATURE AND TYPE OF
3. SURFACTANT
4. CHOLESTEROL CONTENT AND
5. CHARGE
6. RESISTANCE TO OSMOTIC STRESS
7. TEMPERATURE OF HYDRATION
1. Drugs:-Upon entrapment of drugs in niosomes, there is an alteration in the charge and rigidity of the
niosomes bilayers, disrupting the hydrophilic and lipophilic balance of the drugs and affecting the degree of
entrapment.
2. Nature And Type Of Surfactant[9]:- The dimensions of niosomes exhibit a direct correlation to the HLB
value of the surfactant, indicating that an increase in the HLB value of the surfactant, such as span 85, leads to a
proportional increase in the size of niosomes due to the decrease in surface free energy with enhanced
hydrophobicity of the surfactant. A surfactant is characterized by the presence of a hydrophilic head and a
hydrophobic tail, with the hydrophobic portion potentially containing alkyl or perfluoroalkyl groups, or in
specific cases, a single steroidal group.
3. Cholestrol content and charge[10,21]:- The presence of cholesterol aids in enhancing the entrapment
efficiency and hydrodynamic diameter of niosomes by providing membrane stabilizing properties and reducing
membrane permeability. An increase in the cholesterol content of the bilayer may lead to a reduction in the
release rate of the encapsulated material, consequently increasing the rigidity of the bilayers obtained.
Introduction of charge results in an augmented interlamellar distance between successive bilayers within a
multilamellar vesicle structure, contributing to a greater overall volume of entrapped material.
4. Resistance to osmotic stress :-The introduction of a hypertonic salt solution to the niosomes suspension
results in a reduction of their diameter.
5. Temperature of Hydration :- The size and shape of niosomes are dependent on the temperature during
hydration.
3. Osmotic shock[14] :-
Changes in vesicle size can be assessed through osmotic studies, where niosome formulations are exposed to
hypotonic, isotonic, and hypertonic solutions for a duration of 3 hours. Subsequent to this incubation period,
alterations in the vesicle size within the formulations can be observed under an optical microscope.
charge on vesicles and their mean zeta potential values, along with standard deviations, are directly obtained
from these measurements.
1. Dialysis Tubing:-
In-vitro drug release is facilitated by placing niosomes in prewashed dialysis tubing that is hermetically sealed.
This tubing is then dialyzed against a suitable dissolution medium at room temperature, and samples are
withdrawn at specific intervals. Ensuring sink conditions is imperative during this process. [17]
2.Reverse Dialysis[19] :-
In this technique, a small dialysis sac containing 1ml of dissolution medium is placed in proniosomes, which
are then introduced into the dissolution medium. This method allows for direct dilution of proniosomes, but it
may not accurately quantify rapid releases. [20]
withdrawn at regular intervals for drug content analysis using appropriate methods (UV, spectroscopy, HPLC,
etc.). Maintaining sink conditions is vital. [10, 21]
Leishmaniasis[22]
Leishmaniasis is a disease characterized by the infiltration of Leishmania parasites into liver and spleen cells.
Niosomes are utilized to achieve high drug concentrations in the body without inducing adverse effects.
TOXICITY OF NIOSOMES:
The toxicity associated with niosomes is dependent on the nature of their components. Non-ionic surfactants
exhibit higher biocompatibility and lower toxicity compared to anionic, amphoteric, and cationic surfactants.
The presence of surfactants in vesicular systems in equivalent amounts significantly reduces the properties of
niosomes. Hofland et al. conducted a study evaluating the toxicity of various surfactants utilized in niosomal
formulations on human keratinocytes. They suggested that ester-type surfactants are less toxic due to enzymatic
degradation of ether bonds. The hemolytic test is utilized to predict surfactant toxicity, with implications for
vesicular systems derived from such assessments. Hofland et al conducted an investigation into the cytotoxicity
of various surfactants utilized in niosomal formulations on human keratinocytes. They also presented a
hypothesis suggesting that ester-based surfactants are less harmful due to enzymatic breakdown of ether bonds.
The hemolytic assay was employed to assess the toxicity of surfactants, and vesicular systems were developed
based on these findings. Recent studies have shown that the ability of niosomes to disrupt red blood cells
depends on the length of the alkyl chain in the surfactant and the size of the colloidal particles in suspension.
Shorter carbon chains tend to insert more effectively into erythrocyte membranes, disrupting their molecular
structure; however, niosomes encounter challenges in interacting with biological membranes, resulting in
significant hemolysis. Niosomes formulated with bolaform surfactants demonstrated favorable safety and
tolerability profiles both in vitro with human keratinocytes and in vivo with human subjects, who did not
exhibit skin redness when treated topically with a drug-free bolaformniosome formulation.
The movement of drugs through the stratum corneum layer predominantly involves passive interactions and can
occur through three pathways: intercellular, transcellular (paracellular), and transappendageal. Once penetrated
the epidermis, a substance may undergo dermal diffusion or be transported to deeper tissues. [30] Numerous
approaches have been evaluated for their ability to overcome the barrier function of the stratum corneum and
enhance drug delivery into the skin. Specifically, penetration enhancers may operate through one or more of
three potential mechanisms according to the lipid-protein-partitioning theory: they can modify the intercellular
lipid arrangement among the corneocytes to increase diffusivity; alter intracellular protein regions within the
stratum corneum and potentially enhance drug partitioning into the skin tissue. [31] Over the past decade,
niosomes have been extensively studied for transdermal drug delivery and are emerging as promising carriers
for active substances targeted at the skin layer. Niosomes are gaining popularity in the field of dermal drug
delivery due to their unique characteristics and properties induced by their presence in a formulation, such as
enhanced drug penetration, local depot for sustained drug release, and a rate-limiting barrier for modulation of
systemic drug absorption through the skin. [32]
CONCLUSION:
Niosomal drug delivery system represents a significant advancement in the pharmaceutical field, demonstrating
a noteworthy evolution in drug delivery technologies and nanotechnology. It stands out as the preferred dosage
form due to its cost-effectiveness and inherent stability. The utilization of niosomes offers promising
opportunities for delivering encapsulated toxic anticancer drugs, anti-infective agents, and anti-AIDS
medications. Niosomes are favored for their ability to enhance bioavailability and targeting features, ultimately
aiding in minimizing drug toxicity and adverse effects. The strategic integration of niosomes into dosage forms
enables precise targeting of specific tissues within the body.
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