A Review: Proniosomes as a Novel Drug Delivery System

 

Jangam Payal R, Thombre Nilima A, Gaikwad Pallavi N

Department of Quality Assurance Technique, MET’s BKC Institute of Pharmacy, Adgoan, Nashik-422101.

*Corresponding Author E-mail: payalrjangam@gmail.com

 

ABSTRACT:

Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of traditional drug delivery systems and are able to deliver drug at the site of action and at predetermined rate which increases therapeutic efficacy, minimize adverse or side effects and increases bioavailability of the drug. Drug delivery system using colloidal particulate carriers such as liposomes and niosomes have distinct advantages over conventional dosage forms. However, remain significant problems like instability in general application of liposomes and niosomes for drug delivery. In recent time, proniosomal and niosomal system have been received a great attention in drug delivery applications as well as in pharmaceutical research. In order to minimize the problems associated with niosome physical stability such as aggregation, fusion and leaking and to provide additional convenience in transportation, distribution, storage and dosing etc, a dry product can be prepared, which is called proniosome. Proniosomes are dry formulation using suitable carrier coated with nonionic surfactants and can be converted into niosomes immediately before use by hydration. These proniosome-derived niosomes are as good as or even better than conventional niosomes. The current review deals with the trends, different aspects and the future perspective in the development of proniosomal drug delivery systems. (1, 2)

 

KEY WORDS: Niosomes, pronisomes, surfactant, stability, bioavailability.

 


 

INTRODUCTION:

Delivering drug with a controlled rate and targeted delivery received much attention in recent years. The application of nanotechnology to medicine has provided the development of multifunctional nanoparticles that, acting as drug carriers, can be loaded with different drugs. A nanocarrier present a great approach in drug delivery with promising features such as protection of drug from degradation and cleavage, controlle drelease, and in case of targeted delivery approaches the delivery of drug molecules to the target sites.

 

Drug delivery systems using colloidal particulate carriers such as liposomes or niosomes have proved to possess distinct advantages over conventional dosage forms because the particles can act as drug reservoirs, can carry both hydrophilic drugs by encapsulation or hydrophobic drugs by partitioning of these drugs into hydrophobic domains and modification of the particle composition or surface can adjust the drug release rate and/or the affinity for the target site.

 

The vesicles in a dispersed aqueous system may suffer from some chemical problems associated with degradation by hydrolysis or oxidation as well as physical problems as sedimentation, aggregation, or fusion of liposomes during storage. To overcome the limitations (especially chemical and physical stability) of vesicular drug delivery systems like liposomes, niosomes, transferosomes, and pharmacosomes, the pro-vesicular approach was introduced

This includes:

A. Proliposomes

B. Pro-niosomes

C. Dry granular liposomes

D. Mixed micellar proliposomes

E. Pro-transferosomes. (5, 6, 9)

 

Niosomes:

Niosomes are non-ionic surfactant vesicles that are capable to entrap hydrophilic as well as lipophilic drug candidates because they have an infrastructure consisting of both hydrophilic and hydrophobic moieties together. Niosomes are also osmotically active, stable, providing the stability of entrapped drug. They are advantageous than other vesicles as being cheap and chemical stability.The size of niosomes is microscopic and lies in nanometric scale. The particle size ranges from 10-100 nm. Transdermal therapeutic systems have generated an interest as these systems provide the considerable advantage of non-invasive parental routes for drug therapy, avoidance of first-pass gut and hepatic metabolisms, decreased side effects and relative ease of drug input termination in problematic cases. (14,21)

 

Salient features:

Niosomes serve as drug depots in the body which release the drug in a controlled manner through its bilayer providing sustained release of the enclosed drug.  Niosomes are amphiphillic i.e. both hydrophilic and lipophillic in nature and can accommodate a large number of drugs with a wide range of solubilities. The formulation is in the form of aqueous vehicle based suspension having greater patient compliance when compared to oily dosage forms. Niosomes provide advantage of usage through various routes viz. oral, parentral, topical, ocular etc. Niosomes are osmotically active and stable and also increase the stability of the entrapped drug. The surfactants used and also the prepared niosomes are biodegradable, biocompatible and non-immunogenic. Handling and storage of surfactants does not require any special conditions. The characteristics and the performance of the prepared niosomes can be controlled by altering the composition, concentration of various additives, size, lamellarity and surface charge of vesicles.

 

LIMITATIONS:

Niosomes also suffer from some limitations:

1. Physical instability;

2. Aggregation;

3. Fusion;

4. Leaking of entrapped drug; and

5. Hydrolysis of encapsulated drugs which limits the shelf life of the dispersion.

Hence to overcome the drawback, the researchers are focus on the development of proniosomes and converted them into niosomes. (13, 18)

Structure of Niosomes:

 

Fig: 1. Structure of Niosomes

 

Proniosomes:

Proniosomes are dry formulation of water-soluble carrier particles that are coated with surfactant and can be measured out as needed and dehydrated to form niosomal dispersion immediately before use on brief agitation in hot aqueous media within minutes. The resulting niosomes are very similar to conventional niosomes and more uniform in size. For transdermal delivery, proniosomes are the best vesicular system because they act as a drug reservoir for a prolonged period of time and increases skin permeation. The formulation of drugs into proniosomes also helps in better physical and chemical stability of the drug and the vesicular nature of the delivery system helps the drug to permeate through skin with an ease and helps in reaching systemic circulation and the target site without losing any drug activity and providing better therapeutic efficacy. Proniosomes are dry, free flowing, water soluble carrier particles which are coated with surfactant and can from niosomal dispersion on subsequent hydration with hot water. This avoids the problems related to aqueous niosomal dispersion especially leaking, aggregation and fusion. Moreover, proniosomes are stable during sterilization as well as storage. Thus distribution, ease of transfer and storage stability make proniosomes a promising novel delivery system.

 

Structure of Proniosomes:

These are microscopic lamellar structure. They combine a non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class, lipid and cholesterol followed by hydration in the aqueous media. The surfactant molecule directs themselves such that the hydrophilic end of the non- ionic surfactant orient outward, while the hydrophobic end are in the opposite direction to form the bilayer. Like liposomes proniosomes are also made of bilayer. In proniosomes this bilayer are made up of non-ionic surface active agent. On the basis of method of preparation proniosomes are unilamellar or multilamellar.

 

Formation of niosomes from proniosomes:

The niosomes are generally prepared from the proniosomes by adding the aqueous phase to the proniosomes with brief agitation at a temperature greater than the mean transition phase temperature of the surfactant. (12)

 

Fig: 2. Schematic representation of formation of niosomes

 

Advantages of Proniosomes over Niosomes:

1. Avoiding problem of physical stability like aggregation, fusion, leaking.

2. Avoiding hydration of encapsulated drugs which is limiting the shelf-life of the dispersion.

3. Convenience of the transportation, distribution; storage and designing would be dry niosomes a promising industrial product.

4. Furthermore, unacceptable solvents are avoided in proniosomal formulations.

5. The storage makes proniosomes a versatile delivery system with potential for use with a wide range of active compounds. (11, 19)

 

Types of proniosomes:

1.      Dry Granular proniosomes:

According to the type of carrier and method of preparation of dry powder proniosomes are

i.       Sorbitol based proniosomes

ii.      Maltrodextrin based proniosomes

 

Sorbitol based proniosomes is a dry formulation that involves sorbitol as a carrier which is further coated with non-ionic surfactant and is used as a niosomes within a minute by addition of hot water followed by agitation. These are normally made by spraying surfactant mixture prepared in organic solvent on to the sorbitol powder and then evaporating the solvent, the process is required to be repeated till the desired surfactant coating has been achieved. In sorbitol based proniosomes size distribution is very uniform. It is useful in case where the active ingredient is susceptible to hydrolysis.

 

The residual sorbitol decreases the entrapment efficiency to less than one half of that observed without sorbitol. These necessitate reduction in proportion of carrier in final niosomal susupension. The difficulty lies in testing of sorbitol particles because sorbitol is soluble in chloroform and organic solvents. It is prepared by slow spraying method. Maltrodexrin based proniosomes prepared by fast slurry method. Time required to produce proniosomes by slurry method is independent of the ratio of surfactant solution to carry out. Proniosomes of high surface to carriers ratio can be prepared. The method of obtaining niosomes from such a proniosomes for the drug deliver is very simple. An analogue process with the sorbitol results in a solid, surfactant /sorbitol cake. Since maltrodextrin morphology is preserved hollow blown maltrodextrin particles can be used for significant gain in surface area. The higher surface area results in thinner surfactant coating, which makes the rehydration process efficient. This preparation has potential of application in delivering of hydrophobic and ampiphilic drugs.

 

Liquid Crystalline Proniosomes:

When the surfactant molecule is kept in cintact wit water, there are three ways through which lipophilic chains of surfactants can be transformed into a disoederd, liquid state called lyotropic liquid crystalline state (near phase). These three ways are increasing temperature at Kraft point (Tc) addition of solvent which dissolves lipids and use of both temperature and solvent. Near phase or lamellar phase contains bilayers arranged in a sheet over one another within intervening aqueous layer. This type of structure gives typical X-ray diffraction and thread like birefringment structure under polarized microscope. For ternary lecithin, non-ionic surfactant as monoglycerides and alcohol system, lamellar liquid crystals are formed at Kraft temperature in presence of alcohol. The lamellar crystalline phase is converted into dispersion of niosomes at higer water concentration. The organization of liquid/ ethanol/water mixture into lamellar structure can be conveniently utilized for transderma delivery of drug. The liquid crystalline proniosomes and proniosomal gel act as reservoir for transdermal delivery of drug. The transdermal patch involves aluminium foil as abaking material along with the plastic sheet (of suitable thickness stuck to foil by means of adhesive).  Proniosomal gel is spread evenly on the circular plastic sheet followed by covering of nylon mesh.

 

This method avoids the use of pharmaceutically unacceptable solvents and it is easy to scale up. These systems may directly formulate into transdermal patch; up hydration with water from skin it may be converted into niosmes. As the formulation is in direct contact with skin, it itself act as apenetration enhancer. Liquid crystalline proniosomes display number of advantages:

i.       Stability

ii.      Higher entrapment efficiency

iii.    As a penetration enhancer

iv.    There is o disruption of membrane properties of stratum corneum

v.      Easy to scale up as no process is involved moreover it avoid the use of pharmaceutical unacceptable additives

vi.    Amenable to direct fabrication of transdermal patch and does not require dispersion of vesicle into polymer matrix.


 

Materials used for preparation of proniosomes:

Table No. 1

Sr. No.

Class

Examples

Uses

1

Surfactant

-Alkyl ethers and alkyl glyceryl ethers

-Sorbitan fatty acid esters

-Polyoxyethylene fatty acid esters

-Polyoxyethylene 4 lauryl ether (Brij30), Polyoxyethylene cetyl ethers (Brij 52, 56, 58), Polyoxyethylene stearyl ethers (Brij 72, 76)

- Span 20, 40, 60, 80

- Tween 20, 40, 60, 80

To increase the drug flux rate across the skin

2

Carrier material

Maltodextrin, Sorbitol, Mannitol, Spray dried lactose, Glucose monohydrate, Lactose monohydrate, Sucrose stearate

-Penetration enhancer

-Provides flexibility in surfactant and other component ratio

-Altars the drug distribution

3

Membrane stabilizers

-Cholesterol

-Soya and egg Lecithin

-To prevent leakage of drug from formulation

-Skin permeation

4

Solvent

Ethanol, methanol, propanolol, isopranolol,

Skin permeation

5

Aqueous phase

Hot water, pH 7.4 buffer, 0.1 % glycerol

Entrapment efficiency

 


 

Components of Proniosome:

A. Surfactants:

Surfactants are the surface-active agent usually organic compounds that are amphiphilic in nature (having both hydrophobic and hydrophilic groups). They have variety of functions including acting as solubilizers, wetting agents, emulsifiers and permeability enhancers. The most common non-ionic amphiphiles used for vesicle formation are alkyl ethers, alkyl esters, alkyl amides and esters of fatty acids.

 

B. Carrier Material:

The carrier when used in the proniosomes preparation permits the flexibility in the ratio of surfactant and other components that incorporated. In addition to this, it increases the surface area and hence efficient loading. The carriers should be safe and non-toxic, free flowing, poor solubility in the loaded mixture solution and good water solubility for ease of hydration.

 

C. Membrane Stabilizer:

Cholesterol and lecithin are mainly used as membrane stabilizer. Steroids are important components of cell membrane and their presence in membrane brings about significance changes with regard to bilayer stability, fluidity and permeability. Cholesterol is a naturally occurring steroid used as membrane additive. It prevents aggregation by the inclusion of molecules that stabilize the system against the formation of aggregate by repulsive steric or electrostatic effects.

 

It leads transition from the gel state to liquid phase in noisome system. Phosphatidylcholine is a major component of lecithin. It has low solubility in water and can form liposomes, bilayer sheets, micelles or lamellar structures depending on hydration and temperature. Depending upon the source from which they are obtained they are as named as egg lecithin and soya lecithin. It acts as stabilizing as well as penetration enhancer. It is found those vesicles composed of soya lecithin are of larger size than vesicle composed of egg lecithin probably due to the difference in the intrinsic composition.

 

D. Solvent and Aqueous Phase:

Alcohol used in Proniosome has a great effect on vesicle size and drug permeation rate. Vesicles formed from different alcohols are of different size and they follow the order:

 

Ethanol > Propanol > Butanol > Isopropanol. Ethanol has greater solubility in water hence leads to formation of highest size of vesicles instead of isopropanol which forms smallest size of vesicle due to branched chain present. Phosphate buffer pH 7.4, 0.1% glycerol, hot water is used as aqueous phase in preparation of proniosomes.

 

E. Drug:

The drug selection criteria could be based on the following assumptions.

1. Low aqueous solubility of drugs.

2. High dosage frequency of drugs.

3. Short half life.

4. Controlled drug delivery suitable drugs.

5. Higher adverse drug reaction drugs. (1, 3, 9, 18)

 

METHODS OF PREPARATION OF PRONIOSOMES:

Spraying method:

Proniosomes were prepared by spraying the surfactant in an organic solvent into sorbitol powder and then evaporating the solvent. Because the sorbitol carrier is soluble in the organic solvent, it is necessary to repeat the process until the desired surfactant load has been achieved. The surfactant coating on the carrier comes out to be very thin and hydration of this coating allows multilamellar vesicles to form.

 

Advantages:

1. Simple method suitable for hydrophobic drug without concerns of instability or susceptibility of active pharmaceutical ingredient to hydrolysis.23

 

Disadvantages:

1. If the coating of surfactant solution was applied too quickly, the sorbitol particles would degrade and sample becomes viscous slurry.24

2. Sorbitol is found to interfere with encapsulation efficiency of drug.

3. This method was reported to be tedious since the sorbitol carrier for formulating proniosomes is soluble in the solvent used to deposit the surfactant

 

Slurry method:

Proniosomes were produced by slurry method by using maltodextrin as a carrier. The time required to produce proniosomes by this is independent of the ratio of surfactant solution to carrier material. In slurry method, the entire volume of surfactant solution is added to maltodextrin powder in a rotary evaporator and vacuum is applied until the powder appears to be dry and free flowing. Drug containing proniosomes-derived niosomes can be prepared in manner analogous to that used for the conventional niosomes, by adding drug to the surfactant mixture prior to spraying the solution onto the carrier (sorbitol, maltodextrin) or by addition of drug to the aqueous solution used to dissolve hydrate the proniosomes.

 

Advantages:

1. Maltodextrin is a polysaccharide simply soluble in water and it is used as carrier material in formulation, it was easily coat the maltodextrin particles by simply accumulation of surfactant in organic solvent to dry maltodextrin.22

2. Due to uniform coating on carrier it protects the active ingredients and surfactants from hydrolysis and oxidation etc.

3. The superior surface area results in a thinner surface coating, which makes the rehydration development more efficient. (15)

 

Disadvantages:

1. Method is time consuming and involves specialized equipment with vaccum and nitrogen gas.

2. The thin film approach allows only for a predetermined lot sizes so material often wasted so minute quantities or small dose batch can be tedious one.

 

Coacervation phase separation method:

In this method, accurately weighed amount of surfactant, carrier (lecithin), cholesterol and drug are taken in a clean and dry wide mouthed glass vial (5 ml) and solvent is be added to it followed by simple mixing. To prevent the loss of solvent, the open end of the glass vial can be covered with a lid and heated over water bath at 60-70ºC for 5 minutes until the surfactant dissolved completely. The mixture should be allowed to cool down at room temperature till the dispersion gets converted to a proniosomes.

 

Advantages:

1. Method is easy and without time consumable so it does essential specialized equipment.

2. Specially adopted for gel preparation.26

3. Little quantities or small dose formulation can be prepared on lab scale. (1, 2, 19, 22)

 

Characterisation of proniosomes:

1.      Vesicle morphology:

Vesicle morphology involves the measurement of size and shape of proniosomal vesicles. Size of proniosomal vesicles can be measured by dynamic light scattering method in two conditions: without agitation and with agitation. Hydration without agitation results in largest vesicle size. Scanning electron microscopy (SEM) can also be used for the measurement of vesicle size and shape. Determination of vesicle size is important for the topical application of vesicles. Size of captopril vesicles was found after agitation of dispersion as energy applied in agitation resulted in the breakage of the larger vesicles to small vesicles. The size of captopril vesicles was found 11.38-25.06 mm (without tagitation) and 4.14-8.36 mm (with agitation). Hence, it can be concluded that increasing hydrophobicity of the surfactant monomer leads to a smaller size vesicle, since surface energy decreases with increasing the hydrophobicity. (9, 14)

 

2.      Shape and surface morphology:

Surface morphology means roundness, smoothness and formation of aggregation. It was studied by scanning electron microscopy (SEM), optical microscopy, transmission electron microscopy (TEM). (16)

 

3.      Scanning Electron Microscopy:

The proniosomes are sprinkled onto the double-sided tape that is to be affixed on aluminum stubs. The aluminum stub is placed in the vacuum chamber of a scanning electron microscope. The samples are observed for morphological characterization using a gaseous secondary electron detector (working pressure: 0.8 tor, acceleration voltage: 30.00 KV) XL 30. (16)

 

4.      Optical Microscopy

The niosomes are mounted on glass slides and viewed under a microscope with magnification of 1200X for morphological observation after suitable dilution. The photomicrograph of the preparation also obtained from the microscope by using a digital SLR camera. (1,6,9)

 

5.      Transmission Electron Microscopy:

The morphology of hydrated niosome dispersion is determined using transmission electron microscopy. A drop of niosome dispersion is diluted 10-fold using deionized water. A drop of diluted niosome dispersion is applied to a carbon coated 300 mesh copper grid and is left for 1 min to allow some of the niosomes to adhere to the carbon substrate. The remaining dispersion is removed by adsorbing the drop with the corner of a piece of filter paper. After twice rinsing the grid (deionized water for 3-5 s) a drop of 2% aqueous solution of uranyl acetate is applied for 1 s. The remaining solution is removed by absorbing the liquid with the tip of a piece of filter paper and the sample is air dried. The sample is observed at 80 kv.(16)

 

6.      Measurement of Angle of Repose:

The angle of repose of dry proniosomes powder was measured by a funnel method. The proniosomes powder was poured into a funnel which was fixed at a position so that the 13mm outlet orifice of the funnel is 5cm above a level black surface. The powder flows down from the funnel to form a cone on the surface and the angle of repose was then calculated by measuring the height of the cone and the diameter of its base. (11)

 

7.      Encapsulation Efficiency:

The encapsulation efficiency of proniosomes is determined after separation of the unentrapped drug.

 

Separation of Unentrapped Drug is Done by the Following Techniques:

(a) Dialysis:

The aqueous niosomal dispersion is dialyzed tubing against suitable dissolution medium at room temperature then samples are withdrawn from the medium at suitable time interval centrifuged and analyzed for drug content using UV spectroscopy. (19)

 

(b) Gel filtration:

The free drug is removed by gel filtration of niosomal dispersion through a sephadex G50 column and separated with suitable mobile phase and analyzed with analytical techniques. (2, 19)

 

(c) Centrifugation:

The niosomal suspension is centrifuged and the surfactant is separated. The pellet is washed and then resuspended to obtain a niosomal suspension free from unentrapped drug. (4, 6)

 

8.      Determination of Entrapment Efficiency of Proniosomes:

The vesicles obtained after removal of unentraped drug by dialysis is then resuspended in 30% v/v of PEG 200 and 1 ml of 0.1% v/v triton x-100 solution was added to solubilize vesicles the resulted clear solution is then filtered and analyzed for drug content. The percentage of drug entrapped is calculated by using the following formula:

 

Percent Entrapment = Amount of drug entrapped/total × 100 (14, 15)

 

9.      In-Vitro Methods for Assessment of Drug Rele ase from Proniosomes:

(a) Dialysis Tubing:

This apparatus has prewashed dialysis tubing, which can be hermetically sealed. The dialysis sac is then dialyzed against a suitable dissolution medium at room temperature; the samples are withdrawn from the medium at suitable intervals, centrifuged and analyzed for drug content using suitable method (UV spectroscopy, HPLC etc.). The maintenance of sink condition is essential. (7,13,18)

 

Fig:3 Dialysis Tubing

(b) Reverse Dialysis:

In this technique, a number of small dialysis tubes containing 1 ml of dissolution medium are placed. The proniosomes are then displaced into the dissolution medium. The direct dilution of the proniosomes is possible with this method; however, the rapid release cannot be quantified using this method. (19)

 

(c) Franz Diffusion Cell:

The in-vitro studies can be performed by using Franz diffusion cell. Proniosomes are placed in the donor chamber of a Franz diffusion cell fitted with a cellophane membrane. The proniosomes is then dialyzed against suitable dissolution medium at room temperature; the samples are withdrawn from the medium at suitable intervals, and analyzed for drug content using suitable method (UV spectroscopy, HPLC etc.). The maintenance of sink condition is essential. (20, 21)

 

Fig: Franz Diffusion Cell

 

10.   Zeta Potential Analysis

Zeta potential analysis is done for determining the colloidal properties of the prepared formulations. The suitably diluted proniosomes derived niosome dispersion is determined using zeta potential analyzer based on Electrophorectic light scattering and laser Doppler Velocimetery method. The temperature is set at 25°C. Charge on vesicles and their mean zeta potential values with standard deviation of 5 measurements are obtained directly from the measurement. (3,4,9)

 

11.   Osmotic shock:

This study is important to assess the change in vesicle size viewed under optical microscope after incubation with hypnotic, isotonic, hypotonic solutions for 3 hrs. (15, 17, 12)

 

12.   Stability Studies:

Stability studies are carried out by storing the prepared proniosomes at various temperature conditions like refrigeration (2°-8°C), room temperature (25°± 0.5°C) and elevated temperature (45°C ± 0.5°C) from a period of one month to three months. Drug content and variation in the average vesicle diameter are periodically monitored. ICH guidelines suggest stability studies for dry proniosomes powder meant for reconstitution should be studied for accelerated stability at 75% relative humidity as per international climatic zones and climatic condition. (10,21,26)

 

APPLICATIONS OF PRONIOSOME DERIVED NIOSOMES:

1.      Targeting of bioactive agents:

One of the most useful aspects of proniosomes is their ability to target drugs to particular area. Proniosomes can be used to target drugs to the reticulo-endothelial system. The reticulo-endothelium system (RES) preferentially takes up proniosomes vesicles. [10] The uptake of proniosomes is controlled by circulating serum factors called opsonins. Such localization of drugs is utilized to treat tumors in animals known to metastasize to the liver and spleen. This localization of the drugs can also be used for treating parasitic infections of the liver. Proniosomes can also be utilized for targeting drugs to organs other than the RES. A carrier system (such as antibodies) can be attached to proniosomes (as immunoglobin bind readily to the lipid surface of the noisome) to target them to specific organ. (5, 8)

 

2.      Anti-neoplatic treatment:

Most of the antineoplastic drugs cause severe side effects. Proniosomes can alter the metabolism; prolong circulation and half life of the drug, thus decreasing the side effects of the drugs. Proniosomal entrapment of doxorubicin and methotrexate showed beneficial effects over the unentrapped drugs, such as decreased rate of proliferation of the tumor and higher plasma levels accompanied by slower elimination.(6)

 

3.      Leishmaniasis:

Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of the liver and spleen. Commonly prescribed drugs for the treatment are derivatives of antimony (antimonials), which in higher concentrations can cause cardiac, liver and kidney damage. Use of niosomes in tests conducted showed that it was possible to administer higher levels of the drug without the triggering of the side effects and thus allowed greater efficacy in treatment. (1,11)

 

4.      Transdermal drug delivery delivery:

The major drawback of transdermal route of delivery is slow penetration of drug through skin, and increase in the penetration rate has been achieved by transdermal delivery of drug incorporated in niosomes. (12).

 

5.      Cosmetic delivery:

The first report of non-ionic surfactant vesicles came from the cosmetic applications devised by L‟Oreal. Niosomes were developed and patented by L‟Oréal in the 1970s and 80s. The first product Niosome‟ was introduced in 1987 by Lancôme. The advantages of using niosomes in cosmetic and skin care applications include their ability to increase the stability of entrapped drugs, improved bioavailability of poorly absorbed ingredients and enhanced skin penetration. (10)

 

6.      Hormone delivery:

The in-vitro permeation of estradiol from vesicular formulations through human stratum corneum was studied. The vesicles were composed of non-ionic n-alkyl polyoxyethylene ether surfactants (CnEOm). Two mechanisms are proposed to play an important role in vesicle–skin interactions, i.e., the penetration enhancing effect of surfactant molecules and the effect of the vesicular structures caused by their adsorption at the stratum corneum suspension interface.

 

7.      Uses in studying immune response:

Proniosomes are used in studying immune response due to their immunological selectivity, low toxicity and greater stability. Proniosomes are being used to study the nature of the immune response provoked by antigens.

 

8.      Proniosomes as carriers for haemoglobin:

Moser et al., (1989) conducted the study with taking niosome as a carrier for haemoglobin within the blood and suggested that the pronoisome vesicles can be used as carrier for haemoglobin in aneamic patients as pronoisome is permeable to oxygen.

 

9.      Other Applications:

a.      Sustained Release:

Sustained release action of niosomes can be applied to drugs with low therapeutic index and low water solubility since those could be maintained in the circulation via niosomal encapsulation.

 

b. Localized Drug Action:

Drug delivery through niosomes is one of the approaches to achieve localized drug action, since their size and low penetrability through epithelium and connective tissue keeps the drug localized at the site of administration. Localized drug action results in enhancement of efficacy of potency of the drug and at the same time reduces its systemic toxic effects e.g. Antimonial encapsulated within niosomes are taken up by mononuclear cells resulting in localization of drug, increase in potency and hence, decrease both indose and toxicity. The evolution of niosomal drug delivery technology is still at an infancy stage, but thistype of drug delivery system has shown promise in cancer chemotherapy and anti- leishmanial therapy. (14, 21)

 

CONCLUSION:

Proniosomes niosomes are very promising as drug carriers. Compared to liposomes of natural or synthetic phospholipids; niosomes have the advantage that chemical degradation problems, such as oxidation and hydrolysis, may be largely alleviated. Compared to liposome or niosome suspensions, proniosomes represent a significant improvement by eliminating physical stability problems, such as aggregation or fusion of vesicles and leaking of entrapped drugs during long-term storage. Compared to niosomes prepared by conventional means, proniosome-derived niosomes are superior in their convenience of storage, transport and dosing. The release data indicate that proniosome-derived niosomes are at least as effective as conventional niosomes in their release characteristics, and may therefore offer improved bioavailability of some drugs with poor solubility, controlled release formulations, or reduced adverse effects of some drugs. Because proniosomes are a dry powder, further processing is possible. To provide convenient unit dosing, the proniosome powder may be processed to make beads, tablets, gel or capsules. One of the greatest advances offered by proniosomes is their ease of use. Proniosome derived niosome suspensions appear to be as good as or better than conventional noisome preparations, and may be an appropriate preparation to use as a hydrophobic drug carrier.

 

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Received on 26.05.2017       Accepted on 14.07.2017     

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2017; 7 (3): 166-174.

DOI: 10.5958/2231-5713.2017.00027.7