Niosomes: A more promising tool to load poorly penetrating drug through skin for the treatment of Acne vulgaris

 

Avinash V, M. S. Umashankar*, Damodharan N

Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur-603203.

 

ABSTRACT:

Acne vulgaris is a disease, a formation of comedones, papules, nodules, cysts. Acne develop on face and upper trunk and it mostly often affects adolescents. Niosomes is a non-ionic surfactant-based vesicle. It plays vital position in drug delivery system. They can reduce toxicity and bio-availability. Topically carrying out niosomes can increase the residence time of drugs. Niosomes which helps to neutralize damage-causing free radicals, protecting skin cells. A topical antioxidant preparation based on niosomes was prepared to overcome the poorly penetrating drugs and more efficacy in the treatment of Acne vulgaris.

 

 

INTRODUCTION:

Acne vulgaris:

Skin inflammation is an endless ailment of the pilosebaceous follicle that influences for the most part young people. Acne vulgaris causes a type of lesions i.e (polymorph cutaneous). It may leaves scars after regression and it is defined by the alteration of intervals of exacerbation and stability.¹ Spontaneous regression typically happens after age 20, but some sufferers may preserve suffering at some stage in adult life. The most common drug used to the treatment for Acne vulgaris in a form of Transdermal i.e Benzoyl peroxide Gel.^2,3 The reason for using gel formulation they are generally more active and stable and water-based gel being less irritant, so it is preferred than lotions.

 

Causes:

1.     Excess production of sebum (oil) from sebaceous gland.⁴

2.     Bacteria

3.     Hormonal imbalance

4.     Dead skin cells

5.     Ingrown hairs.

 

Niosomes:

Niosome are microscopic synthetic vesicles consisting of an aqueous core bounded in bilayers comprises cholesterol and few non-ionic surfactant.⁵ Here, assessment of hydrated molecules of non-ionic surfactant forms vesicles^5,6. The drug is delivered directly towards the area of process, lead to depletion of medication toxicity. Niosomes are bio-degradable, non-carcinogenic and non-immunogenic. Niosomes is a non-ionic surfactant-based vesicle. It assumes more significant to the drug delivery system.⁷ Niosomes were originally advanced as substitute to liposomes in form to dispatch their drawbacks: (cost effective and good stability).⁵ It increases the skin permeability of medication when locally administered.

 

Structure of niosomes:

Niosomes have microscopic lamellar structure ranging within 10 to 1000nm⁸ composition of cholesterol and non-ionic surfactant formed on admixture of Alkyl polyglycerol ether classes.^9,10 characteristic of niosomes like their size, shape and fluidity can be without problems managed via changing in structural composition and technique of manufacturing. Novel medication delivery system, were the infused medication in a vesicle made out of a bilayer of non-ionic surface dynamic agents.¹¹

 

Fig. 1 Acne

 

Types of niosomes:

Based on Lamellarity:

1.     Multilamellar vesicles (MLV) 1-5 μm in size.^{9, 12}

2.     Large Unilamellar vesicles (LUV) 0.1 – 1μm in size

3.     Small Unilamellar vesicles (SUV) 25 – 500 nm in size.

 

Based on size:

1.     Small Niosomes (100 nm – 200 nm)

2.     Large Niosomes (800 nm – 900 nm)

3.     Big Niosomes (2 μm – 4 μm)

 

 

METHODOLOGY:

Materials used for preparation of niosomes:

Alkyl ethers, Alkyl esters, Alkyl amides, Fatty acids, Lipidic components, Charged molecules.¹⁰

 

General mechanism in preparation:

 

Types involved in preparation of niosome

1.     Ether injection method (EIM)

2.     Hand shaking method (HSM)

3.     Reverse phase evaporation method (REV)

4.     Trans membrane pH gradient

5.     The "Bubble" method

6.     Microfluidization method

7.     Niosomes are formed from proniosomes (Proniosome technology (PT))

8.     Heating method (HM)

9.     Sonication

10. Multiple Membrane Extrusion method

11. Emulsion method

12. Lipid Injection method

 

Ether injection method:

1.     This strategy depends on moderate surfactant infusion : cholesterol arrangement in ether over 14 gauge needle in to a preheated fluid stage kept up at 60℃.

2.     Vaporisation of ether bringing about to a development of ether angle at ether-water interface that prompts single layered vesicles arrangement.

3.     Based on the utilized conditions, the vesicles breadth ranges between 50 to 1000nm.¹³

 

Hand shaking method:

1.     It is also called as Thin-Film Hydration method.

2.     Cholesterol and surfactant are dissolved in a volatile natural solvent (Chloroform, diethyl ether or methanol) in round bottom flask.

3.     The natural solvent is evacuated under vaccum at room temperature utilizing rotary evaporator leaving a thin layer of solid mixture deposit on the sides of the flask.

4.     The dried surfactant film can be rehydrated with fluid stage at temperature marginally over the phase transition temperature of the surfactant utilized, with delicate agitation.

5.     Large multilamellar niosomes are formed by this process.

Reverse phase evaporation technique (rev):

 

1.     Surfactant and cholesterol (1:1) are dissolved in a combination of chloroform and ether.

2.     An aqueous phase containing medication is added to this and the resulting two phases are sonicated at 4-5℃.

3.     The natural part is evacuated at 40℃ under low weight. The resulting viscous niosome suspension is dilute with PBS and warmed on a water bath at 60℃ for 10 minutes to yield niosomes.¹³

 

Trans membrane pH gradient:

 

1.     Cholesterol and surfactant are dissolved in chloroform.

2.     The solvent is then evaporated beneath reduced pressure to get a thin film on the sides of the round bottom flask.

3.     The film is hydrated with 300 mm citric acid (pH 4.0) by vortex mixing.

4.     The multilamellar vesicles are frozen and increased multiple times and next sonicated. To this niosomal suspension, aqueous solution consists of 10mg/ml medication is added and vortexed.

5.     The pH of the sample is then raised to 7.0-7.2 along disodium phosphate.

6.     This mixture is next warmed at 60℃ for 10 minutes to form niosomes.

 

Niosomes:

The bubble method:

1.     This strategy is utilized for one step liposomes and niosomes formation without the natural solvents utilization.

2.     The bubbling unit comprise of round bottom flask with three necks situated in water bath for control of temperature.

3.     Water-cooled reflux and thermometer is situated in the first and second neck and nitrogen supply through the third neck.

4.     Surfactant and cholesterol are scattered together in this buffer (pH7.4) at 70℃, scattering combined for 15 seconds with high shear homogenizer and quickly thereafter bubbled at 70℃ by nitrogen gas utilization.

 

Micro fluidization method:

In this strategy two fluidized streams (one consists of medication and the other surfactant) collaborate at high speed, in precisely characterized small scale channels inside the communication chamber, so the method for the vitality provided to the system stays in the region of niosomes improvement. It brings about better consistency, littler size and reproducibility in the niosomes formulation.

 

Formation of niosomes from proniosomes:

1.     Another methodology to produce niosomes is to cover a water solvent transporter, for instance, sorbitol with surfactant.

2.     The resultant of the covering methodology is a dry definition. In which each water dissolvable particle is verified with a thin film of dry surfactant. This arrangement is named as "Proniosomes".

3.     The niosomes are surrounded by the development of watery stage at T>Tm and brief fomentation.

 

Where

T= Temperature

where T_m= mean phase transition temperature

Heating method:

In this combination with non-ionic surfactant, cholesterol, and charge-including atoms is added to a liquid medium within the sight of a polyol, for example, glycerol. The combination is warmed until vesicles are shaped while mixing by magnetic stirrer.¹³

 

Sonication:

Cable describes the formation of vesicles in the solution by using sonication phenomenon. It includes the addition of surfactant to buffer containing drug solution in a 10ml vial. Titanium test is used by sonicating the mixture at 60℃ for 3 minutes to obtain nisomes.¹³

 

Multiple membrane extrusion method:

1.     Cholesterol alongside Diacetyl phosphate and surfactant should be dissolved in chloroform.

2.     Evaporation of solvent should to be done to form a thin film.

3.     To the above mixture drug solution should be included.

4.     This mixture is allows to pass through a series of membranes i.e eight-Polycarbonate layer.

5.     This leads the formation of niosomes.

 

Emulsion method:

1.     Organic solution of surfactant and cholesterol is added to drug solution.

2.     Oil in water type of emulsion is separately prepared.

3.     Evaporation of organic solvents.

4.     The niosomes are dispersed in to aqueous phase.

 

Lipid injection method:

1.     A mixture containing lipid and surfactant is melted and injected in to aqueous phase of drug, which is highly agitated and heated.

2.     In this the drug is dissolved in molten lipid.

3.     This combination is injected in to an aqueous phase, which contains surfactant and noisome will be obtained.^{10, 13}

 

Mechanism of niosome penetration through skin:

Not a single appliance that could adequately clarify the niosomes capacity for medication expand through the skin, and a few mechanism were suggested, including: modification of the barrier activity of stratum corneum, because of reversible lipid association disorder; decrease of trans epidermal water lack, which builds stratum corneum hydration and relaxes them firmly stuffed cell structure and ingestion or potentially niosomes combination on the layer of the skin, as uncovered by freeze fracture electron microscopy and small angle X-ray dissipating, prompting a high thermodynamic action slope of medications at the interface, which is the main inducing for medication penetration.

 

Niosomes adsorption on to the cell layer happens with practically zero internalization of lipid or aqueous components it might occur either because of pulling in physical force or result of combined by distinct receptors to ligands on the vesicle layer and move of medication straight from vesicles to the skin. Then again, niosomes are combined with the membranes of cell, bringing about complete mixing of the niosomal substance with the cytoplasm. At last, niosomes might be immersed by the cell (endocytosis), with lysozymes present in the cytoplasm lowering or processing the membranous structure of the niosomes, along these lines discharging the seduced material in to the skin.¹⁴

 

Fig. 2 Possible mechanism of actin of niosomes as skin drug delivery systems

 

 

 

Poorly penetrating drugs through skin for treatment for acne vulgaris

 

·       The above-mentioned drugs have high molecular weight and low permeability

·       To overcome this problem niosomes are used.

·       Niosomes have high penetration and can easily reach the required site.

·       Niosomes acts as a protecting layer or a coating layer to the drug and releases the drug only at desired area in the body.

·       Benzoyl peroxide having more effective than other drugs in a form of lotion. And also less disadvantages than others.

 

Advantages of niosomes:

·       It is one of the promising drug delivery systems.

·       It can be applied topically and enhances the residence time of the drug in stratum corneum.

·       They also increases the horny layer properties by decreasing trans epidermal water loss.

·       Niosomes are osmotically active, chemically stable and have long storage.

·       They have high compatibility with low toxicity and biological systems

·       They are biodegradable, non-immunogenic and non-carcinogenic.

·       They can entrap lipophilic drugs into vesicular bilayer membranes and hydrophilic medications in aqueous compartments.

·       The therapeutic activity of medication molecules are increased by protecting them from biological atmosphere.⁸

 

Evaluation of niosomes:

The formed niosomes are characteristic based on particle size and particle distribution, lamellarity, encapsulation efficiency, and Zeta potential. The size and distribution of the particles were determined using a PSA, lamellarity was determined using TEM, efficacy of encapsulation was determined using a UV.V is spectrophotometer and Zeta potential was determined using the Zeta sizer.¹⁹

Size and distribution:

The size and distribution of niosomes is measured by diluting 1 drop of the niosomes diluted in 30 ml of aquadest. The size of the majority of niosomes was 338.3 nm, and the particle distribution showed a polydispersity index of 0.349.^19,20

 

Lamellarity:

It is determined using copper to absorb the niosome particles from the suspension. They were stained with 0.2% Uranyl acetate in ddH2O for 1 minute and dried-specimens were absorbed under the TEM at 80 KV.²⁰

 

Entrapment efficacy:

The entrapment of efficacy of encapsulation of green tea was determined by calculating the amount EGCG encapsulated in niosomes.⁷ EGCG not absorbed in the supernatant was measured at 275nm. It Is denoted as EE.^13,20

 

                    TOTAL drug added – TOTAL free drug

EF[%] = ––––––––––––––––––––––––––––––––––––––– × 100

                                  TOTAL drug added

 

Transmission electron microscopy:

TEM is utilized for selecting the shape, size and lamellarity of niosome. In a word, a suspension is prepared and mixing with one percent of phosphotungstic Acid. A drop of resultant was then utilized on carbon coated matrix, depleting off the overflow and after that the matrix was observed. Pictures are taken under reasonable magnification under TEM.¹⁹

 

Zeta potential:

The Zeta potential is a key pointer of the colloidal scatterings stabilities. The size of the Zeta potential exhibits the degree of electrostatic shock between close by, similarly charged particles in a dispersing.¹⁹

 

 

 

Stability test:

The capacity of the vesicles to hold the active substance was determined by putting away the niosomal suspension under various temperature conditions. Tests were regularly tried (for 14 days) for active substance content, in the way depicted in encapsulation capability procedure.¹⁹

 

CONCLUSION:

Niosomes have greatly increased the use of transdermal drug delivery system. It prove that the drugs which have low penetration efficacy can be transported to the desired amount by niosomes. There are various scope used to infuse toxic anti-cancer medications, anti-AIDS medications, anti-viral medications by niosomes and to utilize them as promising carriers for medications. The ionic medication carriers are unsuitable and relatively poisonous while niosomal carriers are more safer. Some drugs have high molecular weight and low permeability to overcome this problem niosomes are used. Niosomes have high penetration efficacy and they encapsulate the drugs, which can easily penetrate through different layers of skin. Hence, niosomes is considered as one of the best medication carriers for the treatment of Acne vulgaris.

 

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Accepted on 20.02.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(6): 3035-3040.