Nanoliposomes: Synthesis methods and applications in cosmetics.

Just Accepted by Journal of Cosmetic and Laser Therapy

Nanoliposomes: Synthesis Methods and Applications in Cosmetics Zohreh Fakhravar , Pedram Ebrahimnejad, Hadis Daraee, Abolfazl Akbarzadeh Doi: 10.3109/14764172.2015.1039040 Abstract J Cosmet Laser Ther Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 05/18/15 For personal use only.

Nanotechnology used more frequently in marketing of skin care goods, and whereas the word sounds similar to it belongs in robotics and science fiction, it is rapidly becoming a truth in medicine and skin care. As few people actually recognize what the technology, benefits or what the possible implications of its use are, we determined to make this outline. The type of nanotechnology that is most significant in the good looks, skin care and health parts is the use of nanoparticles (Or Bucky balls as they are known in the manufacturing), and it is a particular kind of these nanoparticles that have been touted as the next generation of Liposomes. Nanoliposomes are one of the most recognized names for the nanoparticles used in skin care and cosmetic products, and we are also well-known with the term liposome, so this connection between the two is the perhaps the best way to clarify what Nanoliposomes are. In this paper, some of the appropriate techniques for their produce are reviewed. It’s usually used methods of nanoliposomes preparation are discussed.

© 2015 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.

IJCL_A_1039040_Coverpage.indd 1

04-05-2015 11:41:56

Nanoliposomes: Synthesis Methods and Applications in Cosmetics

Zohreh Fakhravar 1, Pedram Ebrahimnejad1*, Hadis Daraee3, Abolfazl Akbarzadeh2,3,4* 1

Faculty of Pharmacy, Mazandaran University of Medical Sciences,Sari,Iran, 2Drug

Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, 3

Department of Medical Biotechnology, and Medical Nanotechnology, School of

Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran, J Cosmet Laser Ther Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 05/18/15 For personal use only.

4

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

*Correspondence: Pedram Ebrahimnejad, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran, and Dr. Abolfazl Akbarzadeh, Drug Applied Research Center, Tabriz University of Medical Sciences, 5154853431 Tabriz, Iran. Tel/Fax: +984133341933. E-mail: [email protected] , and [email protected] Abstract Nanotechnology used more frequently in marketing of skin care goods, and whereas the word sounds similar to it belongs in robotics and science fiction, it is rapidly becoming a truth in medicine and skin care. As few people actually recognize what the technology, benefits or what the possible implications of its use are, we determined to make this outline. The type of nanotechnology that is most significant in the good looks, skin care and health parts is the use of nanoparticles (Or Bucky balls as they are known in the manufacturing), and it is a particular kind of these nanoparticles that have been touted as the next generation of Liposomes.Nanoliposomes are one of the most recognized names for the nanoparticles used in skin care and cosmetic products, and we are also well-known with the term liposome, so this connection between the two is the perhaps the best way to clarify what Nanoliposomes are. In this paper, some of the appropriate techniques for their produce are reviewed. It’s usually used methods of nanoliposomes preparation are discussed.

Keywords: Nanoliposomes, Skin Care, Nanoparticles, Cosmetic Products.

Introduction Nanotechnology has the likely to be used in different ways in the cosmetics sector, controls materials on an remarkably minuscule size so nano materials are used in cosmetics to give them new characteristics. creating nano materials with different properties and therefore different risks and advantages.

J Cosmet Laser Ther Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 05/18/15 For personal use only.

Nanoliposomes are nanometric version of liposomes which are atomic, liquid-filled bubbles whose walls are made of layers of phospholipids analogous to the phospholipids that make up cell membranes in our skin and are one of the most applied encapsulation and controlled release systems. The word liposome derives from two Greek words, lipos (fat) and soma (body or structure), which meaning a structure in which a fatty encapsulates internal aqueous structure(s) 1Liposomes ,which are ideal models of cells and biomembranes, can be tradition designed for approximately any need by changeable the lipid substance, size, surface charge and method of preparation, making them suitable for delivery systems for drugs, vitamins and cosmetic materials.2Liposomes is applied to the skin, becausetheir resemblance to biological. Active ingredients are encapsulated in the Liposomes, when the active solution entrapped within, the Liposomes begin to combine with the cellular membranes.3 In the progression, the Liposomes free their payload of active materials into the cells. As a result, not only is release of the actives very specific: directly into the intended cells; but the deliverance takes place more a longer period of time. The disadvantages with conventional large, liposomes (Typically 1 micron in size) are that they are actually liposomes within liposomes, and have a limited capacity to enter narrow blood vessels or into the skin to a importantlevel.4 Accordingly, some

of the materials that are captured in the inner layers of these liposomes can in definitessituationsare nearly un-releasable. Nutracosmeticsis a rising class of health and beauty aid products. They combine the advantages of nutraceutical in gradients with the grace, skin sense and delivery systems of cosmetics. Nutracosmetics and cosmeceuticals thus differ in the foundation of their functional ingredients.5Today, consumers worldwide are in searching


of personal care products that provideseveral benefits with leastattempts. They alongsideswait for the latest technology progress to be incorporated into novel formulations. Faced with these tendencies, formulators struggle to extend highly differentiated multifunctional products that focus on cure as well as aesthetics.6 A significant number of novel products are based on a new generation of active ingredients. With these emerging actives, come a range of formulation challenges that includes constancy control and the complications of combining several actives into a single cosmetic product. As a discipline that concerns with the cure of non-pathological skin, up to date cosmetology is progressively more alternating with dermatology.7 Introducing Nanolipoomes:

Nanoliposmes (or nanoparticles) are very small, single or double bilayer liposomes that are so small they are measured in the Nanometer range,8 and are approximately 800 times smaller (Typically 50 Nanometers in size) than the diameter of the human hair.9Nanoliposomes can be up to twenty times smaller than liposomes, dependant on type, and these tiny, and they are composed from much higher quality phospholipids ingredients than the commercial lecithin that larger liposomes are created from, some with higher percentages of phosphatidylcholine (PC), one of the essential components of

membranes.10

cell

Lecithin, a commonly used source for Liposomes typically contains only 1020% phosphatidylcholine, it’s the higher-grade materials that make up the nanoliposomes are believed to possess more mammalian molecular characteristics than conventional liposomes,11 they possess greater nonantigenic properties and are more biodegradable Some of the processes to


create nanoliposmesinclude the use of high-pressure Supercritical fluids or subjecting

large,

multiple-layer

liposomes

to

ultrasonic

energy.12Consequently, the cost to produce Nanoliposomes is more expensive than conventional liposomes.This process can be used to incorporate drugs, vitamins, nutrients to the structure of nanoliposomes. 13Selection of a suitable method of nanoliposomes preparation is not arbitrary and depends on the follow in parameters: 1) Physicochemical properties of the medium in which the lipid vesicle are scattered; 2) shelf- life, optimum size, and polydispersity of the vesicles; 3) potential toxicity, effective concentration substances which are entrapped in nanoliposomes.14 The same properties of Nanoliposomes can be utilized also in the delivery of ingredients incosmetics,15 and as a carrier itself offers advantages becauselipids are well hydrated and can reduce the dryness of the skin for reason exist oflinolenic acid which is a primary cause for its ageing.16 The field of cosmetics and skin care products is clearly the most inventive rapidly evolving area of dermatology.17Nowadays skin care formulations must meet high standards of efficacy - preferably visible effects for the consumers are much more sophisticated than in the past. As a result,

consumers expect and demand real performance from their products. To ensure effectiveness of the cosmetic formulation, the actives have to be transported to the target site, mostly into the epidermis.But penetration of substances through the skin is limited by the natural barrier the stratumcorneum with its “brick and mortar” architecture.

18

Indeed, the

interstices in the horny layer, which seldom exceed more than 20 nm in


width, are extremely impermeable even for small molecules.19 Depending on the composition, a vehicle is used to exert mainly five types of effects on the skin cleansing, decoration, care, hydration and protection. Delivering active substance to the targeted site requires the right concentration of actives in the formulation to achieve the optimal release rate and desired distribution of active substances between the vehicle and target site.20 A cosmetic care product has to be developed and whenever this is the case, various issues and aspects have to be considered such as site and area of application, sensory and optical properties, state of matter, actives and final product storage stability and packaging. Delivery systems. Some of the important novel cosmetic delivery systems are discussed (Table 1). 21 Front-running brands of nanocosmetics: A nanocosmetic is one area of fastidious notice as new types of manufactured goods can be prepared using nano materials. UV filters used in sunscreens produced in nano shape, for example, become clear relatively than white when contrasted to their larger form. But, there’s ambiguity about whether, beside the alters that bring consumer benefits; some of these materials could present new risks.

Materials could be more hazardous and behave differently in the body compared to larger forms. Cosmetics giant Estee Lauder entered the NanoMarket in 2006 with a range of products containing “NanoParticles”. L’Oreal, the world's major cosmetics company, is devoting about $600 million dollars, of its $17 billion dollar revenues, to Nano patents, and has patented the use of dozens of “nanoliposome elements”.


There is a broad spectrum of nanoparticles in the pharmaceutical and cosmetic field (Figure 1): "Liquid" or“Fluid" nanoparticles 

Liposomes

A liposome is a tiny bubble (vesicle) and an artificially-prepared spherical vesicle made out of the same material as a cell membrane (Their structure is derived from natural cells) and is the bilayer variant of nanoparticles. Liposomes can be packed with drugs and other biological materials, and can be used to deliver drugs for cancer and other diseases. Membranes are usually prepared by phospholipids, which are molecules that have a head and a tail groups. The head is attached to water, and the tail (which made of a long hydrocarbon chain) is dis-attracted by water.22, 23 •

Membrane containing nanoparticles:

They are oil builds with lipid soluble active bodies that are encapsulated by a phosphatidylcholine (PC) membrane. This sometimes also called as nanosomes. Phospholipid nanosomes are nanoparticles

and

uniform

liposomes

manufactured

utilizing

supercritical fluid skills. semi-empirical experiments and Mathematical modeling show that the character and size of phospholipid

nanosomes rely on the several material properties and different process factors including bubble size, the size and design of decompression nozzle, interfacial forces, pressure and the rate of decompression, the nature of compound being encapsulated and charge distribution24, 25 

Chylomicrons:


Chylomicrons are lipoprotein bodies that contain of phospholipids, cholesterol, proteins and triglycerides. They deliver dietary lipids from the intestines to other parts in the body and the lymphatic system. They are natural delivery systems for lipids in the lymphatic system of the body. 26 Solid nanoparticles: •

Nano or microcapsules:

The nano-microcapsules drug delivery system is currently as a promising technique for the treatment of many different types of diseases, particularly tumors and cancerous cells.27In this case, controlled release of the active agents out of the polymer matrix can be achieved by using Nano or microcapsules. •

Metal oxides:

Oxide nanoparticles can shows unique chemical and physical properties because of their restricted a high density and size of edge or corner surface sites. Titanium dioxide nanoparticles are employed as a mineral sun protection. In the field of cancer therapy, ferrousoxide nanoparticles are injected and then selectively carrying to the tumor tissue and are heated by magnetic fields and thus damage the tumor tissue. 28

•

Hydrocarbons and waxes (Lip pearls):

These organic additives in combination with cosmetic active agents and in aqueous dispersions are melted at high temperatures adjusted to the needed particle size in a homogenization procedure and then cooled down. After this process, solid nanoparticles will form a nanoparticles which also known as solid lipid nanoparticles or SLN.29


Types of nanomaterials used in cosmetics are the following •

Liposomes

Commonly, Liposomes are artificially constructed spherical vesicles consisting of a phospholipid bilayer with particle sizes ranging from 30 nm to several micrometers, which made of concentric bilayered vesicles enveloping aqueous units consisted of natural or synthetic phospholipids. 30, 31 Liposomes can fuse with other bilayers such as the cell membrane because of having the polar head groups which oriented in the pathway of the interior and exterior aqueous phases.

32

These properties making them useful for

cosmetic delivery applications that can be created from natural nontoxic phospholipids such as cholesterol. The main advantage of liposomes are enhanced absorption of active ingredients by skin , and continuous supply of agents into the cells over a sustained period of time as well as Their ease of preparation, which make them suitable for cosmetic applications. Other liposome-related structure are Vesicles, which being used these days that claim to further enhance the penetration of substances across the skin such as ethosomes, niosomesand transferosomes .

Nanoemulsions: Nano-emulsion (also referred to as smallemulsions, especially fine emulsions, submicron emulsions) are emulsions of nanoscale droplets of one liquid within another whose structure can be influenced based on the method of synthesis. this droplets are shaped by mechanical shearing of the continuous phase in order to smash larger droplets of the dispersed phase into


smaller droplets. Nano-emulsion droplet typically have sizes in the range of 20–200 nm and show narrow size distributions.33 Because of having their smaller particle size, they can be used to carry active ingredients and provide higher stability and better suitability, and finally increase the shelf life of the product. Nanocapsules: Nanocapsules are submicroscopic colloidal drug carrier systems that are composed of a thin polymer membrane or capsule surrounding an aqueous or oily core. Such nanocapsules are obtained by using two technologies; the interfacial nano deposition of a preformed polymer or the interfacial polymerization of a monomers studies has been found the penetration of UV filter octylmethoxycinnamate in pig skin can be decreased by using of nanocapsules when compared with conventional emulsions.34

Nanocrystals: Drug nanocrystals are nanoparticles with a crystalline character which have a size in the nanometer range. They are made of an aggregate complex involving several hundred to tens of thousands of atoms that combine into a “cluster”. Studies have shown They can be safe and effective for deliver and passage


through skin.35 Nanocrystals can increase dissolution velocity and bioavailability because of two reasons: Increase of dissolution velocity by surface area enlargement and Increase in saturation solubility.36 Dendrimers: Dendrimers are unimolecular, monodisperse, micellarnano structures branched, around 20 nm in size, with a well-defined, frequently branched symmetrical structure and a high density of functional end groups at their periphery and a synthetic polymers with layered architectures that show promise in several biomedical cosmetics applications. They are suiteable for multifunctionalization because of having contain large number of external groups.37 It is easily possible to precisely control molecular weight and chemical composition of dendrimers by regulating dendrimer synthesis, thereby allowing

predictable

tuning

of

their

biocompatibility

pharmacokinetics.38 Methods of nanoliposomes preparation (Figure 2)39 MICROFLUIDIZATION:

and

Microfluidizer exists in microfudics Corporation, Massachusetts, USA. A design plant based on this technology can invention about 20 gallon/minute of liposomes in 50-200 nm size range. This

method

based

on

microfuidization/

homogenization/

microemulsification was build up for the organization of liposomes.

40

The encapsulation effectiveness of up to 75% could be attained. 14


Aqueous scatterings of liposomes often have trend to merge or combine and may he prone to hydrolysis and or oxidation.14 At first we selected a appropriate suspension medium and components of the nanoliposomes (depending on the planed application), Then we Placed the nanoliposomes ingredients in the suspension medium, followed by the correct mixing of the sample by stirring We Placed the achieved in the previous step suspension in a reservoir, and set proper procedure parameters such as flow rate air intake, and operating pressure, the size of interaction chamber, and the number of passes. After setting procedure parameters, the air valve was opened, which in turn leaded to liquid scattering which flowed throughout a filter into the interaction chamber.14 The dispersion was split in two streams in interaction chamber and they interacted at very high velocities in dimensionally defined microchannels. Subsequently, the obtained suspension can be recycled via the equipment (several passes arise during nanoliposomes production, usually 3 or 4 before receiving final product). Before the next passing, the suspension had to be cooled, on account of temperature rising in interaction chamber.41 In the final step, nanoliposome suspension departed the apparatus at temperature above the transition phase in inert

atmosphere including nitrogen or argon for 1 h, which finally lead to annealing and stabilizing of sample.40 EXTRUSION: This technique in the dilute suspension of liposome (composed of liquid crystalline lipid) can be passed sequentially through filters of decreasing pore size.42 Extrusion can be performed using a hand-held syringe fitted with a


standard sterilization filter holder. This method, is limited by the back pressure that can be tolerated by the syringe and filter holder, in addition to the pressure that can be applied manually. At first we prepared a sample consisting of micrometric liposomes (MLV), which were modified for the next stages of the liposome Placement of one or two-stacked polycarbonate filters into the stand/heating block onto a hot place, and then inserting a thermometer into a wall in the heating block.43 The liposome suspension should be kept above the phase transition temperature of the lipids this principle the hot plate needs to be switched filling the syringe fully with buffer, and then passing through the extruder; the aim is to reduce the dead volume. In the following step, the buffer is removed putting the liposome suspension into one of the syringes (donor syringe) of the extruder; subsequently carefully placing the syringe into one end of the device by applying a gentle twisting. In the next stages, placing the second syringe (receiver syringe) into the other last part of extruder also previous to starting next stages, make sure that receiver syringe plunger is set to zero.41 Placing the fully assembled device into the extruder stand. Follow inserting the stainless-steel hexagonal nut in such way that any two opposing apexes fall in the vertical plane. In order to ensure good thermal contact between syringes and heating block, swing-arm clips should be used Within about 5-

10 minutes temperature of nanoliposomes suspension reaching the temperature of the heating block.43 The contents of the filled syringe are transferred to the empty syringe by pushing the plunger slightly and slowly. The next step includes gently pushing the plunger of the alternate syringe to transfer the suspension back into the original syringe.43 In order to obtain nanoliposomes of the desired properties, extrusion process should be


repeated. The number of passages through filters is always odd, the minimum number of passes is seven after the end of extrusion, the extruder should be taken out of the heating block, and after that the filled syringe must be removed from the extruder. The attained nanoliposomes example should be injected into a clean vial In a following stage, the extruder parts can be cleaned first by rinsing with ethanol, and then with distilled water. 42The final step includes keeping nanoliposomes at temperature above transition phase under inert atmosphere such as nitrogen or argon for 1 h, which ultimately leads to annealing and stabilizing the sample.44 SONICATION TECHNIQUE: Liposomes can be formed by the use of ultrasonic. The basic materials for liposome preperation are amphilic molecules derived or based on biological membrane lipids.44 For the configuration of small unilamellar vesicles (SUV), the lipid dispersion is sonicated gently – e.g. with the handheld ultrasonic device UP50H (50W, 30kHz), the VialTweeter or the ultrasonic reactor UTR200 – in an ice bath. The length of such an ultrasonic handling lasts approx. 5 – 15 minutes .A different technique to produce small unilamellar vesicles is the sonication of the multi-lamellar vesicles liposomes. Dinu-Pirvu et al. (2010) reports the obtaining of transferosomes by

sonicating

MLVs

at

room

temperature.40

Hielscherultrasonics offers various ultrasonic devices, sonotrodes and trimmings to supply the appropriate sonicator regarding power At first dissolve the appropriate combination of the phospholipid components (with or without cholesterol), in either chloroform or in chloroform-methanol mixture. The results mixture should be filtered to remove minor insoluble


components. Additionally, ultrafiltration is used to reduce or eliminate pyrogens.41 Transfer of thesolutionto a flask (pear-shaped or a roundbottom), followed by placing it in a rotary evaporator. The aim is to remove the solvents at temperature above phase transition under negative pressure. 43 This procedure is performed until a thin layer of dried lipid components in the flask is obtained.43 Removal of traces of the organic solvents using a vacuum pump or flushing the flask with an inert gas (e.g. nitrogen or argon).Adding glass beads (e. g with 500 μm diameter) into a flask containing dry lipids and then adding a suitable aqueous phase such as distilled water or buffer. The dried lipids can be dispersed into the hydration fluid by the vortex mixing for 1-5 minutes or hand-shaking the flask. In this stage, micrometric (MLV) type liposomes are obtained subsequently step, flask including MLV is transferred to the probe (tip) sonicator. 42 For purpose probe sonication, place the tip of the sonicator in the MLV flask and sonicate the sample with 20 s ON, 20 s OFF intervals, for a total period of 10-15 minutes. After sonication is carried out properly, we receive the final product nanoliposomes.43 There are can be Potential health hazards with nanomaterials and nanoparticles in Cosmetics.

There is a dubiety of how and where nano materials are being used in cosmetics. There is also uncertainty about how to evaluate them for Safety. Several products are endorsed, but others using nanotechnology don’t tell it. While some materials raise concern, experts advising the management have highlighted potential risks posed by others, mainly insoluble nano materials.


Direct physical contact of consumers with nanomaterials and nanoparticles may be absorbed by the body via ways such as the digestive organs (face or lip applications), the lungs (sprays), eye contacts and the skin.45 Thereby can because of inflammation and/or cell damage as a result of cell cytotoxicity and other cell damages, but the threshold rate and level which the absorbed nanomaterials may be trigger an adverse effect remains unknown and need further studies.46 Nanoliposomes can change the bioavailability and the toxicological behavior of the materials they transport. But before using these agents must apply safety tests on nanomaterials and/or the agents contained within them.47 3 Applications of NanoLiposomes in Cosmetics: In recent years, nanoliposomes have attracted great interest of many researchers in different fields because of their unusual properties of these molecules, such as their biodegradability, biocompatibility and nanosize. 48

Thereby, Due to these properties, they can be widely and acceleratory

applied in many fields, especially as carriers of active agents in food technology, agriculture, nano-therapy as well as cosmetics.49 There are different useful targets (Skin, hair and mucosal surfaces) for the delivery of active compounds such as, botanicals and, importantly, drugs.

The kinds of nano products that are used consist of: 

Sunscreens – UV filters, such as titanium dioxide and zinc oxide, are used in nano type rather than bulk form to make the sunscreen clear rather than white. It is also asserted that they are more useful when used in nano form.



Nano emulsions and nanosomes – used to protect active ingredients,


such as vitamins and anti-oxidants, and their lightness and transparency. 

Fullerenes – new types of materials can be produced using nanotechnology, such as carbon fullerenes. It is claimed that these tiny carbon spheres have anti-aging properties.



Other materials used in nano size – a complete range of materials can be used in nano size in sort to give them special properties when compared with their larger form. in fact an ‘energizing’ moisturiser using nano gold and products using nano silver because of its antibacterial properties.

Encapsulation of these active compounds provides a helpful apparatus to the cosmetic and/or pharmaceutical formulator and thereby providing great flexibility in the choice of delivery methods which can be used such as delivery of active pharmaceutical ingredients in systems that would otherwise be unacceptable to them. Incorporation of active compounds such as Lipophilicinto aqueous dispersions without the need for a solvent can be easily possible. In a study, scientists have shown that Sun Protective and Moisturizing Effects of Nanoliposomes Containing Safranal (Lip-Safranal) could act as a better antisolaragentcompared to homosalate and have no moisturizing effect in 1 and 4% concentrations. The results shown that, the

(Sun protection factors) SPF of liposomes containing 8% safranal (LipSafranal 8%) was extensively higher than 8% homosalate reference.49 It is indicated that, Saffron can act as a sunscreen, but the safranal existing in saffron encapsulated in nanoliposome may have significant sun protective effect in low concentration. SPF of saffron-encapsulated in nanoliposomes 8% extract was considerably higher than standard sunscreen homosalate with


similar concentration.

49

SPFs of safranal (1% and 0.5%) piece of saffron

were considerably higher than the standard sunscreen homosalate8 %.50 in another study, scientist used Chitosan-coated nanoliposome as vitamin E carrier, which is itself bioactive, and made from phosphatidylcholine (pc) and cholesterol by the sonication method. integration of vitamin E (VE) the chitosan-coated liposomes prevented chemical degradation, which is shown The stability of VE-loaded liposomes suspension during the 8 weeks storage is over 90% under 4°C and use of this complex suggest for cosmetic application Sang-Ok Jeon and et all encapsulated recombinant human epidermal growth factor (rhEGF) into nano-liposomes system as aim of topical delivery.51 The rhEGF-loaded nano-liposomes were synthesized using a high pressure homogenization technique. The results of this work have shown the skin permeation and localization of rhEGF were enhanced by nano-liposomes and the nano-liposomes enhanced the permeation and localization of rhEGF in rat skin by enhancing delivery through pores of skin.52 Zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles have been extensively used for several years asUV protection in sunscreens.53 In recent times, nanoparticles of these oxides have turned intowell-known as they keep the UV filtration and absorption properties although eliminating the white

chalky emergence of conventional sunscreens. Products using nanoparticles of ZnO or TiO2 are obvious so have increased aesthetic appeal, are less smelly, less oily and more absorbable by the skin.54 A number of alterations to the standard ZnO or TiO2 UV safety system have beenreported. Oxonica have extended Optisol, a UV absorption system which includes TiO2 and 1 %manganese58. Dispersing carnauba wax nanoparticles with TiO2


nanoparticles was found to raise the sun protection factor (SPF).55 Nanophase Technologies, who provide nanoparticles to companies including BASF, manufacture controllable polymeric nanocrystals of ZnO with a size less than 35 nm for personal care functions.56 Other nanoparticles have been developed for UV protection. Rohm and Haas (www.rohmhaas.com)

manufactureempty

styrene

acrylate

copolymer

nanoparticles, ~300 nm in size, that are reported to increase SPF by about 70 %.

57

Silica nanoshells have been used by Sol-Gel Technologies

(http://www.sol-gel.com) to encapsulate cosmetic elements. Their first product ‘UV Pearls TM’includes UV filters encapsulated in silica shells kept on the top layers of the skin to block UVrays. The product provides progressed photostability and decreases the filter uptake by the skin. Another product, ‘Cool PearlsTMBPO’, encapsulates benzoyl peroxide crystals in the silica shells for acne cure.58 The elements are less than 200 nm in size, soluble in oils and can be used in sunscreens as an different to TiO2 and ZnO.59 Nanotechnology has been used to study the mechanical characteristics of hair.60 Accepting the differences between hair types allow cosmetic companies to generate products to suit personality hair types. The hair care

industry is also interested in the effect of water on the nanomechanical properties of hair.61 Bhusanet al. have conducted nanoscratch tests, using Nano Intender II (MTS Nanosystems), to understand properties of unusual types of hairs at the nanoscale.

62

The studies expressed the difference in scratch resistance of

single hair fibres of different ethnic regions as well as the coefficient of


resistance of hairs. A more study into the hair weakness due to stress and pressure using AFM has shown that the ethnic hairs vary in mechanical properties.63 Conclusion: Nanoliposomes are very complex systems with clear advantages and some disadvantages. Using nanoliposomes in cosmetics improves hydration because of the size of the particles, making the skin soft and elastic. A flexible film of nanoliposomes is formed at the outside of the skin as a substitute of a hard film generated by solid, toxic parabins. Nanoliposomes are harmless, but interest is required in the direction of the side effects of their elimination from the skin. Further studies require to be done to appreciate the organization and dynamics of these nanoparticles. Producers of cosmetics that contain nanomaterials and nano particles say that in accordance with existing authorized requirements their manufactured goods have to be submitted to a security assessment and are therefore protected and safe. However, it is debatable whether the applied testing and analytical methods, in particular for non-soluble and non-degradable nano particles, are suitable for determining the specific risk relevant-properties of nano particles. Adequate in vivo and in vitro testing techniques are now being expanded. Of

definite importanceis the establishment of meaningful dose effect connection, because we do not as yet know the entrance levels that start an effect. Nanoliposomes which really have the ability to transport active substances into the deeper skin layers or even to act as transdermal and systemic drug delivery system are most important in recent years as aim of cosmetic applications.


Consequently, flexible nanoliposomes are the only selection to carry active molecules into the deeper skin layers (biological syringe) by stabilizing the actives and even acting as pharmaceutical or cosmetic component as a result of its chemical nature. Authors ’ contributions ZF conceived of the study and participated in its design and coordination. PE,AA,and HD participated in the sequence alignment and drafted the manuscript. All authors read and approved the final manuscript. Acknowledgments The authors thank the Faculty of Pharmacy, Mazandaran University of Medical Sciences,Sari,Iran. Declaration of interest The authors have no declaration of interest. The e authors alone are responsible for the content and writing of the paper.

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Table 1. Advantages and disadvantages of liposome Liposomes increased efficacy and Low solubility therapeutic

index

of

drug

(actinomycin-D) Liposome

increased

stability

via Short half-life

encapsulation


Liposomes are non-toxic, flexible, biocompatible,

completely Sometimes phospholipid undergoes

biodegradable, and non-immunogenic oxidation for

systemic

and

and

hydrolysis-like

non-systemic reaction

administrations Liposomes reduce the toxicity of the Leakage and fusion of encapsulated encapsulated agent (amphotericin B, drug/molecules Taxol) Liposomes help reduce the exposure Production cost is high of sensitive tissues to toxic drugs Site avoidance effect

Fewer stables

Flexibility to couple with site-specific ligands to achieve active targeting Liposomes reduce the toxicity of the Leakage and fusion of encapsulated encapsulated agent (amphotericin B, drug/molecules Taxol) have not a suitable method for Provide controlled drug delivery Sterilization Biodegradable,

biocompatible, Low Encapsulation efficiency

flexible Non ionic

Lysosoaml degradation

Can carry both water soluble and lipid Not suitable for gene therapy soluble drugs Drug can be stabilized from oxidation Controlled hydration


Improve protein stabilization Provide sustained release Targeted drug delivery and site specific drug

Stabilization of entrapped drug from hospital environment Altered pharmacokinetics and pharmacodynamics Can be administered through various route Act as reservoir of drug Therapeutic index of drug is increased Site of avoidance therapy Can modulated the destitution of drug Direct interaction of drug with cell

Low efficacy active targeting


Figure 1. structure of nano structures which widely used as aim of

nanotechnology works.


Figure 2. methods of liposomes preparation in brief

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