Microemulsions It is a single optically isotropic and thermodynamically stable system of water, oil and an amphiphile

Development Team

Principal Investigator Prof. Farhan J Ahmad

Jamia Hamdard, New Delhi

Paper Coordinator Dr. Javed Ali

Jamia Hamdard, New Delhi

Content Writer Dr. Javed Ali

Jamia Hamdard, New Delhi

Content Reviewer

Dr. Alka Gupta

VP, Medical Services Division, OPL India

Novel technologies in Cosmetic products

Contents:

Emulsion Delivery Systems-Microemulsions, Liquid crystals, Multiple emulsions, Nanoemulsions, solid lipid nanoparticles, nanostructured lipid carrier.

Noninvasive treatment and technology- Cryolipolysis, Laser lipolysis, hair transplant, Cellulite

Other Delivery systems- Carbosomes, Dendrimers and hyperbranched polymers, Nano Crystals

Delivery Devices- Iontophoresis, Cosmetic patches

Novel technology has modernized the cosmetic industry. Latest technology advances has to be incorporated into innovative formulations to keep the cosmetic industry going. A variety of formulations falls in special delivery systems like Emulsion Delivery Systems-Microemulsions, Liquid crystals, Multiple emulsions, Nanoemulsions, solid lipid nanoparticles, nanostructured lipid carrier. Hence, novel cosmaceutical delivery systems explored here shows massive potential as a future generation smarter carrier system.

Microemulsions

It is a single optically isotropic and thermodynamically stable system of water, oil and an amphiphile. They are homogenous, stable liquid dispersions of water and oil. They are stabilized by using an interfacial film of surfactants. The droplets diameter ranges between 100 – 1000 A (10 – 100 nm). There are 4 main components involved in the microemulsion formulations, namely water, oil, surfactant/s and cosurfactants. These phases are shown in Figure 1. Generally non-ionic surfactants are used owing to their excellent cutaneous tolerance and balanced lipophilic and hydrophilic assets. In addition, co-surfactant increases the interfacial fluidity and transforms the Hydrophilic-Lipophilic Balance (HLB) of the surfactant to optimal value. In microemulsions, the active ingredient is not suspended but solubilized that make it available for immediate rapid and effective absorption. They have a good appearance as they are optically transparent and have low viscosity. Microemulsions can solubilize hydrophilic and lipophilic drugs because of the presence of micro-domains of diverse polarity contained by the same single phase solution. The drug can be transported through a barrier, when the system come in contact with the semi-permeable membrane as the drug partitions among continuous and dispersed phase. Based upon the volume of the dispersed phase, the transport and the partition rate of active ingredient, a pseudozero order kinetics drug release can be obtained. A microemulsion has

the ability to enhance the efficacy of the active compound thereby reducing their total dose and side effects.

Figure 1: Different components of microemulsion

In cosmetic industry, microemulsions are considered to be ideal as the moisturizing formulation as they provide occlusivity and fulfill the criteria for artistic appearance. In addition, it also serves the ease for removal from the container, ease of application and adherence to treated area excluding tackiness. A variety of drugs are formularized in the form microemulsion. Few of them can be summed up as below:

 Vitamin E was formulated in the microemulsion form which enhances the moisturizing effect and penetration power of the vitamin.

 Efficacy of the carotenoids was increased by formulating it to the microemulsion for the treatment of skin cancer.

 Pigmentation of the skin is increased by increasing the melanin content of the melanocytes using di- decanoyl in the form of microemulsion

 Anti-aging microemulsion of tri-decyl salicylic acid was way more efficacious as the efficiency of tri-decyl salicylic acid was increased.

 Microemulsion of benzotriazoles, bisesorecinyltriazine and S-triazine was formulated to increase the photoprotective efficacy.

Liquid crystals (LC)

It is a distinct phase of matter which is observed between the crystalline (solid) and isotropic (liquid) states. Although the molecules are arranged in a crystal like manner it may flow like a liquid. This thermodynamically stable crystalline phase shows a state of incomplete melting. LC can further be divided into two groups which have further subgroups (Figure 2). LC revealed birefractive and dichronism, which enhances the cosmetic appeal due to the colored appearance of the formulations into which they are used. Lipophilic materials like vitamins protected from both thermal and photo degradation is attained when built-in as liquid crystalline matrix. It was observed that emulsions having LC has a much slower rate of active release in comparison to those not having. This effect is seen due to Liquid crystalline’s multilayer structure around the droplet that effectively decreases the interfacial transport of the dissolved ingredients within the droplet.

Figure 2: Different Phases of Liquid Crystals

1. Thermotropic: Temperature controlled phase of pure liquid crystals, or mixtures of them are called thermotropic liquid crystals. The Brownian motion of the molecules increases with the temperature, reducing the order in the material. Depending upon the temperature, whether lowered or elevated, they are further divided into two categories:

a. Nematic Liquid Crystal: When the temperature is lowered, the material changes to a nematic phase. This phase may be explained as molecules which have no positional order but they tend to point in the same direction. They are anisotropic materials whose physical properties vary with the average configuration. If the configuration is large, the material is very anisotropic. Similarly, if the configuration is small, the material is almost isotropic. A special class of nematic liquid crystals is known as chiral nematic or chloesteric (both terms are interchangeably used). Chiral refers to the exclusive ability of the molecule to selectively reflect one component of circularly polarized light.

b. Smectic Phases: "Smectic" is a Greek word meaning soap. This apparently mystifying origin may be explained by the fact that the thick, slippery substance which is frequently found at the foot of a soap dish is actually a type of smectic liquid crystal. The major difference from the nematic phase is that it shows a degree of translational order that is not there in the nematic phase. The molecules sustain the common orientational order of

nematics, however they also tend to align themselves in layers or planes. It was observed that within these planes motion is restricted and different planes are observed to flow past each other. Having increased order indicates that the smectic state is more "solid-like"

than nematic. More than a single type of smectic phase is observed in many compounds.

Twelve types of smectic phase variations have been acknowledged, from which some are explained here. In Insmectic-A mesophase, there is no particular positional order is bur director oreints perpendicular to the smectic plane. In the smectic-B mesophase also, director is perpendicular to the smectic plane orients, but here in addition the molecules are arranged into a network of hexagons within the layer. Similar to the smectic-A mesophase, molecules are arranged in the smectic-C mesophase, but here the director is at a constant tilt angle which is measured normally to the smectic plane. The smectic-C mesophase is like the nematic phase that is having a chiral state. Also, same as the smectic-C mesophase, the director makes a tilt angle to the smectic plane. The only difference lies between these is that this angle rotates from layer to layer form a helix. In some smectic mesophases, like Smectic-G, molecules get affected by the various layers present above and below them. Hence, a small amount of three dimensional order is seen.

Characterization of the Liquid Crystals

a. Positional Order: It provides the level up to which an average molecule or group of molecules may show translational symmetry.

b. Orientational Order: explains the measure of the tendency of the molecules to arrange themselves in accordance with the director on a long-range basis.

c. Bond Orientational Order: It explains a line combining the centers of nearest-neighbor molecules with no a regular spacing down that line.

Multiple emulsions

They are the complex systems where drops of the dispersed phase encapsulate smaller droplets that are identical with continuous phase in most of the scenarios, therefore also known as emulsions of emulsions. In multiple emulsions, the internal and external phases are similar and an intermediate phase separates the two like phases. The intermediate phase is immiscible with the two like phases. An emulsifier is present to stabilize the emulsions, which are further categorized as primary emulsifiers (decaglyceroldecaoleate, mixed triglyceroltrioleate and sorbitantrioleate) and secondary emulsifiers (polysorbates and poloxamers). Lipophilic (oil- soluble, low HLB) surfactants are used to stabilize w/o emulsions, whereas hydrophilic (water- soluble, high HLB) surfactants are used to stabilize o/w systems. Mainly there are two types of multiple emulsions, i.e., w/o/w emulsion and o/w/o emulsion, in which w/o/w type of emulsion is used frequently (Shown in figure 3). The main drawback of this system of delivery is the stability, which can be surmounted by designing a polymeric gel in the aqueous phase either internally or externally. In multiple systems, for the transport mechanism of solute, two hypotheses were proposed. The first hypothesis demonstrated that the active ingredient is released in the internal phase by virtue of the rupturing of the multiple oily globules taking place either by shearing or by inflammation. For the second hypothesis, it was established that via the oily membrane encapsulated active substance can be diffused.

In cosmetology, these formulations prevent the degradation of an active ingredient and release it at a controlled rate. In addition, they possess a fine texture and a smooth touch upon application.

They serve as an internal reservoir to entrap matter from the outer diluted continuous phase into the inner confined space. They can also improve dissolutions or solubilization of insoluble materials. Due to these properties, multiple emulsions protect the sensitive and active molecules such as vitamins C and E from the external phase. This process is known as antioxidation.

Figure 3: Multiple emulsion

Nanoemulsions (NE)

They are a colloidal particulate system in the submicron size range acting as carriers of drug molecules having size range of 10-1000 nm. They are solid spheres having amorphous and lipophilic surface with a negative charge as shown in Figure 4. In addition the therapeutic efficacy of the drug is enhanced and adverse effects are minimized. It is a thermodynamically unstable system, which can be stabilized by the presence of an emulsifying agent. The dispersed phase is also known as internal phase or the discontinuous phase while the outer phase is called dispersion medium, external phase or continuous phase. The emulsifying agent is also known as intermediate or interphase. The term ‘nanoemulsion’ also refers to a miniemulsion which is fine oil-in-water or water-in-oil dispersion stabilized by an interfacial film of surfactant molecule having droplet size range 20–600 nm. NEs are transparent because of their small size. Generally, there are 3 types of nanoemulsion namely oil-in-water (oil is dispersed in the continuous aqueous phase), water-in-oil nanoemulsion (water droplets are dispersed in continuous oil phase) and bi- continuous nanoemulsions.

Figure 4: Nanoemulsion sphere

The main ingredient to be taken care during preparation of nanoemulsion is ‘Surfactant’. The concentration of surfactant must be high enough to stabilize the microdroplets to produce nanoemulsion, also it must be flexible.

Characterization of nanoemulsion:

Following parameters judge the stability of the nanoemulsion:

Flocculation and creaming: It is convergence of globules to form a large clump that rises or settle in the emulsion more quickly than the individual globules. The rising up or settling down of dispersed globules to give a concentrated layer is known as creaming. Thus flocculation leads to creaming.

Cracking: It is the separation of the dispersed phase as a layer. Whereas a creamed emulsion may be reconstituted by shaking or agitation, a cracked emulsion cannot be reconstituted.

Cracking represents permanent instability. Cracking of the emulsion may be due to the addition of an emulgent of opposite nature or may be due to decomposition or precipitation of emulgent.

Cracking may also occur by the addition of a common solvent in which both oily and aqueous phases are miscible.

Phase inversion: It is the change in the type of emulsion from oil-in-water to water-in-oil and vice versa. It is a physical process that may bring about by varying the phase volume ratio, addition of electrolytes, and temperature changes.

In addition to flocculation, creaming and cracking, emulsions may also deteriorate if stored under extremely high or low temperature or in the presence of light. Hence emulsions are usually packed in air-tight, colored containers and stored at moderate temperature.

Recently, NE has gain interest as a potential vehicle for the controlled delivery of cosmetics and for the optimized dispersion of active ingredients in particular skin layers due to their own bioactive effects. They are preferred over the liposomes because they are more stable owing to their lipophilic interior. They have the capacity to reduce the transepidermal water loss, indicating that the barrier function of the skin is strengthened. Nanoemulsion is the area of interest in cosmetics because of their low viscosity and transparent visual aspects with droplet sizes below 200 nm, also its high surface area allows the effective transport of the active ingredient to the skin. In addition there is no inherent creaming, sedimentation, flocculation, or coalescence which is observed with macroemulsions. It is quite modern but fast mounting field of application: emulsion-based wet wipes for such applications as baby care and make-up removal.

Solid lipid nanoparticles (SLN)

In 1991, SLNs were introduced as a substitute to the traditional colloidal carrier system like liposomes, emulsions and polymeric microparticles and polymeric nanoparticles. They are sub- micron colloidal carriers having size from 50-1000 nm. SLNs are generally made from physiological lipid which is dispersed in water or aqueous surfactant solution as shown in Figure 5. They offer exclusive properties like small size, large surface area, high drug loading and the interaction of phases at the interface and are attractive for their potential to improve performance of pharmaceuticals. They possess controlled release properties with improved skin hydration and

active penetration and fortification against degradation, for which they are the choice in the cosmetic industry. In addition, they also protect the compounds against chemical degradation and act as occlusive. Depending on the type of release desired, they can be prepared with a drug- enriched shell to have the burst release and for the sustained release drug enriched core is the choice. These characterize a particulate dispersion of solid spherical particle which consists of fatty acid derivative hydrophobic core enclosed by a phospholipid layer.

Figure 5: SLN sphere Nanostructured Lipid Carriers (NLCs)

The introduction of lipid NPs named as NLCs was done in order to overcome the limitations of the SLNs. The major advantage of this type of carrier/delivery system is its ability to incorporate large quantities of drugs as a result of formation of a less ordered lipid matrix with many imperfections. These are prepared by mixing solid and liquid (oil) lipids. Three incorporation models as shown in Figure 6 have been proposed for these carriers depending on the basis of the type of lipid used in their production. In NLCs Type 1, the matrix of the NLCs is unable to form a highly ordered structures resulting in structural imperfections due to the different chain lengths of the various fatty acids and mixture of mono-, di- and triacylglycerols used during their

preparations. In NLCs type II special lipids that do not recrystallize after homogenization and cooling of nanoemulsion are used. In NLCs Type III solid lipids are mixed with oils in such a ratio that the solubility of the oil molecules in the solid lipid is exceeded. On cooling of the nanoemulsion, the lipid droplets reach the miscibility gap resulting in precipitation of oil, thereby resulting in the formation of tiny oil droplets. Subsequent solidification of the solid lipid surrounding these droplets leads to fixation of the oily nanocompartments. Increase in loading capacity for drug of higher solubility in liquid lipids than in solid lipids is the advantage of this model.

Like SLNs, NLCs also has the capacity of preventing the active compounds from chemical degradation. In addition, they showed high occlusion factor with high level of skin adherence property. A thin film layer is created owing to the particle adherence on the skin thereby preventing dehydration. Decrease in the particle size increases the occlusion factor that enables NLCs to control the occlusion without altering other properties. Also, by altering the matrix structure of nanoparticle, release profile of the active ingredients can be influenced. In comparison to the microparticles, lipid nanoparticle enhances the penetration capacities of the active ingredients. In addition, the properties of the lipid nanoparticles like lubricating effect and mechanical barrier are desirable in the application of skin care products as they reduce irritation and other allergic reactions. The appearance of the final product also plays an important role and lipid nanoparticles make the products to appear white in contrast to yellow which is more attractive for the customers.

Figure 6: Different types of NLCs; (a) Type I NLC; (b) Type II NLC; (c) Type III NLC Cryolipolysis

It is a medical treatment used to devastate fat cells. This treatment is based on the principle that adipocytes are more susceptible to cooling than other skin cells. The treatment involves the controlled cooling near 4 °C for the non-invasive localized reduction of fat deposits in order to reshape body contours. Therefore, the technique is also known as ‘Fat freezing’. The exposure to cooling is set so that it causes cell death of subcutaneous fat tissue without apparent damage to the overlying skin. Cold temperatures trigger the death of adipocytes that are subsequently engulfed and digested by macrophages. There are no changes seen in the subcutaneous fat instantly after the treatment. An inflammatory process stimulated by apoptosis of adipocytes, as reflected by an influx of inflammatory cells, can be seen within 3 days after treatment and peaks at approximately 14 days thereafter as the adipocytes become surrounded by histiocytes, neutrophils, lymphocytes, and other mononuclear cells. At 14–30 days after treatment, macrophages and other phagocytes surround, envelope, and digest the lipid cells as part of the body’s natural response to injury. Post four weeks of the treatment, the inflammation lessens and the adipocyte volume is decreased. After 2-3 months of the treatment, the interlobular septa are distinctly thickened and the inflammatory process further decreases. By this time, the fat volume

in the treated area is apparently decreased and the septae account for the majority of the tissue volume.

The FDA approves a cryolipolytic device name CoolSculpting (ZELTIQ Aesthetics, Inc., Pleasanton, CA, USA) for the reduction of flank and abdominal fat in 2010. Also, in April 2014, FDA also approves this system for the treatment of subcutaneous fat in the thighs.

Both animal and human studies are available to prove the safety and efficacy of this treatment.

Two separate studies were conducted on animal models that demonstrated the decrease of up to 1 cm or 40% of the total fat layer thickness after a single exposure without damaging the overlying skin.

In the same way, many studies were conducted on humans; one of them was published in 2009, which involves 10 subjects. The results showed that there was 20.4% and 25.5% reduction in the fat layer after 2 months and 6 months treatment, respectively. From the studies it was demonstrated that cryolipolysis was most effective on abdomen, back and flank. The long-term duration of effect of this treatment has not been evaluated as yet. Also there are no significant adverse events seen because of this treatment. As subcutaneous panniculitis is known to induce with the cold temperatures but there are no such results found during or after the treatment.

Although side effects like erythema, bruising and transient numbness are expected during the treatment which may get resolved within 14 days after the treatment is over.

Nanocrystals

Nanocrystals are crystals having size in naonometric range (approximately between 10-400 nm).

They are generally used to incorporate and deliver the poorly soluble drugs in cosmetics as they may provide high penetration power through dermal application. They are amassed encircling several hundreds to thousands of atoms that are combined to form a "cluster" which must be stabilized to prevent the formation of larger aggregates. An additional advantage with the

nanocrystals is that they are composed of 100% drug only and there is as such no carrier material present in polymeric nanoparticles (PNPs). Nanosuspension is formed as a result of dispersion of drug nanocrystals in liquid media on the contrary to “macrosuspensions” or “microsuspensions”.

Generally, by the use of surfactants of stabilizers the dispersed particles need to be stabilized.

Here, the dispersion media may be used as aqueous or non-aqueous media (like liquid polyethylene glycol [PEG], oils, etc.).

Iontophoresis

It has gained interest in last two decades for the both systemic and topical delivery. It is a physical process in which ions flow diffusively in a medium driven by an applied electric field into the intact skin and the underlying tissue. Generally low molecular weight hydrophilic solutes are delivered at the site of action. It is a dynamic way of distributing active agent into the skin and ultimately attaining improved cosmetic benefits in variety of skin disorders. It is widely used in ophthalmology, dermatology, ENT, allergic conditions even in situations like cardiac and neurological, however its supreme advantage is in the transport of protein which are otherwise very difficult to transport transdermally owing to their large molecular size and hydrophilicity.

Using the appropriate composition of electrical current with the appropriate active ingredient may prove to be beneficial in the treatment of aesthetic skin disorders like melasma, hyperpigmentation, aged skin, acne scars etc. A typical Iontophoresis device consists of an electrical power source, electrodes and an active agent in an appropriate carrier.

Iontophoresis works on the general principle that like charges repels each other while unlike charges attract and basiclally works on water soluble substances having positive or negative charge i.e. IONS. An ion can be ‘pushed’ into the skin by using a direct current. It is noted that the electrode being used should have the same charge as the ion of concern, i.e. a positive ion

(cation) will be pushed into the skin by a positive electrode (anode) and a negative ion (anion) will be pushed by a negative electrode (cathode).

There is variety of working electrodes present that includes rollers, balls, disks etc. As direct current is used, another electrode is required to complete the electrical circuit and get the current to flow. This electrode of concern can be a bar, provided to the patient to hold, or it can be a pad that is to placed somewhere to make a good body contact, like may be under the shoulder or wrapped around the upper arm etc.

The earliest use of iontophoresis was by Helena Rubinstein a salon practice in 1935, but was later discovered that the technique was already used as a treatment regime in French salons.

Customers were possibly given the treatment on the general idea that it would enhance the penetration of the cream or gel being used on the face or body treatment. During the course of treatment, production of heat may cause the skin reddening which would later be explained as regeneration of the skin. Today also, the same explanation is used with the clients i.e. the treatment triggers the circulation of blood which enhances the levels of oxygen and nourishment supplied to the skin. Today in the modern world, as an iontophoretic ingredients vitamins, minerals, collagen, elastin, amino acids, hyaluronic acid are used in salon treatments. Therapists have the minimal information on working of the technique, besides the fact that the skin condition on which they are to be applied and the polarity of the electrode to be used.

Cosmetic patches

Cosmetic patches are used as delivery systems in the cosmetology and not as simple cosmetic forms. They symbolize a suitable, effortless, secure and efficient way for cosmetic applications, by means of one of the most adequate, contemporary and thriving delivery systems. They are the fashionable dermal delivery systems that satisfy the body's need for essential vitamins and other important elements thereby allowing therapeutically active constituents to be transdermally

administered. There are many layers in such conventional patches i.e. the 1^st layer is the backing layer (provides protection to the patches from atmosphere) accompanying the tightly fixed adhesive layer to the support layer that rarely encloses one or more active component. They are to be used in the same way as the classic cosmetic products were used. A cosmetic patch can be categorized in many ways like a patch form (matrix/reservoir), application for expected results (moisturizing, anti-wrinkles), structural materials (synthetic, natural and hybrid), based on the duration of application (overnight, half-hour patch). Human clinical study revealed the fact that using a single patch for 20 min can results in a visible reduction of the quantity and intensity of wrinkles under the eye and also it lasted for several hours. A short term effect like skin smoothening is resulted from the occurrence of a slight, subclinical inflammatory response. In contrast the long-term effects like rejuvenation may have resulted from tissue stimulation, improved respiration, enhanced blood flow, etc.

Laser lipolysis

It is a technique used for the treatment of localized fat and promotion of cutaneous retraction.

Direct application of laser to the adipose tissue results in fat liquefaction, blood vessel, collagen denaturation and coagulation. Neocollagenesis and skin contraction is induced by thermal damage. In comparison to the conventional liposuction, removal of fat by laser lipolysis has a lesser post-operative recovery time and minimum side effects like less pain, bruising, swelling etc. The mechanism of action for the technique is based on the principle of selective photothermolysis. The internal system of controlled energy aims to reach 2 chromophores i.e. fat and collagen.

The direct disclosure of the laser to the target tissue may result in selective thermolipolysis and the thermal denaturation of collagen fibers, thus maintaining the septal architecture which contribute to the elevation in cutaneous retraction. Subcutaneous tissue fat has an optical absorption coefficient of approximately 400 to 1,500 nm. Collagen's optical absorption

coefficient is comparable to that of the water and consequently increases with increase wavelength. The main cause of adipocytolysis and contraction of the skin is the thermal factor.

The liquefied fat depends on the total energy accumulated in the treated area. Therefore, given that the result of the lipolysis and stimulation of collagen depends on the amount of thermal energy accumulated in the tissue, monitoring of the temperature during laser lipolysis is suggested. The external temperature must remain between 40-42ºC for greater effectiveness and to prevent the burns. The internal temperature must reach 48-50ºC in order to cause irreversible adipocytolysis and denaturation of the adjacent collagen, with the resulting stimulation of neocollagenesis. Histological studies have confirmed the clinical benefits resulting from the laser’s action in the skin, including the destruction of adipocytes, the remodeling of collagen, and the coagulation of blood and lymph vessels.

This technique is performed on the patients without being actually hospitalizing them. Before performing the procedure lab investigations like complete blood count, clotting time, liver function test, HIV, hepatitis B, C and other important tests are conducted. The patient should be in the standing position and in the same position pictures and marking of the treatment areas should be carried out. Through a 1-2 mm incision, tumescent local anesthesia is administered to the patient followed by the insertion of 1 mm microcannula containing the laser optical fiber into the subcutaneous plane which is moved back and forth, parallel to the surface, with an average speed of 5 cm/s, 10-15 times in each area.

By the use of the negative pressure, the liquefied fat is typically aspirated with the cannula having small diameter. However, only manual drainage is performed in some cases. Aspiration is not necessary in the treatment of sagging.

Antibiotics and analgesics are prescribed, and patients are instructed to use compression bands specific to each treated area for 15-30 days, and to avoid exposure to the sun for a month.

Physical activity should be avoided for one week, and complementary physiotherapy sessions are

recommended. The patients must be followed up in the first and third months after treatment to evaluate the results.

Hair Transplant

Hair loss or Alopecia is an emerging problem that seems to have trouble both males and females.

Hair transplantation is a surgical technique that moves hair follicles from a part of the body called the 'donor site' to a balding part of the body known as the 'recipient site'. It is primarily used to treat male pattern baldness. In this minimally invasive procedure, grafts containing hair follicles that are genetically resistant to balding, (like the back of the head) are transplanted to the bald scalp.

Hair transplantation can also be used to restore eyelashes, eyebrows, beard hair, chest hair, pubic hair and to fill in scars caused by accidents or surgery such as face-lifts and previous hair transplants. Hair transplantation differs from skin grafting in that grafts contain almost all of the epidermis and dermis surrounding the hair follicle, and many tiny grafts are transplanted rather than a single strip of skin.

Planning and Pre-operative assessment

To begin with, patient’s scalp is analyzed by the surgeons and their preferences and expectations are discussed and the best approach (e.g. single vs. multiple sessions) and expected results are advised. Pre-operative folliscopy will help to know the actual existing density of hair, so that postoperative results of newly transplanted hair grafts can be accurately assessed. Some patients may benefit with preoperative topical minoxidil application and vitamins. For several days prior to surgery the patient refrains from using any medicines which might result in intraoperative bleeding and resultant poor grafting.

Harvesting methods

Transplant operations are performed on an outpatient basis, with mild sedation followed by injecting local anesthesia. The scalp is shampooed and then treated with an antibacterial agent prior to the donor scalp being harvested. Regardless of the harvesting technique, proper extraction of the hair follicle is paramount to ensure the viability of the transplanted hair and avoid transection, the cutting of the hair shaft from the hair follicle. Hair follicles grow at a slight angle to the skin's surface, so transplanted tissue must be removed at a corresponding angle.

There are two main ways in which donor grafts are extracted today: strip excision harvesting, and follicular unit extraction.

 Strip harvesting: It is the most common technique for removing hair and follicles from a donor site. The surgeon harvests a strip of skin from the posterior scalp, in an area of good hair growth. A single-, double-, or triple-bladed scalpel is used to remove strips of hair-bearing tissue from the donor site. Each incision is planned so that intact hair follicles are removed. The excised strip is about 1-1.5 x 15-30 cm in size. While closing the resulting wound, assistants begin to dissect individual follicular unit grafts, which are small, naturally formed groupings of hair follicles, from the strip. Working with binocular Stereo-microscopes, they carefully remove excess fibrous and fatty tissue while trying to avoid damage to the follicular cells that will be used for grafting. The latest method of closure is called 'Trichophytic closure' which results in much finer scars at the donor area. This procedure leaves a thin linear scar in the donor area, which is typically covered by a patient's hair even at relatively short lengths. The recovery period is around 2 weeks and will require the stitches/staples to be removed by medical personnel or sub cuticular suturing can be done.

 Follicular unit extraction (FUE): Individual follicular units containing 1 to 4 hairs are removed under local anesthesia; this micro removal typically uses tiny punches of between 0.6mm and 1.0mm in diameter. The surgeon then uses very small micro blades

or fine needles to puncture the sites for receiving the grafts, placing them in a predetermined density and pattern, and angling the wounds in a consistent fashion to promote a realistic hair pattern. The technicians generally do the final part of the procedure, inserting the individual grafts in place. FUE procedure is more time consuming than strip surgery. An FUE surgery time varies according to the surgeons experience, speed in harvesting and patient characteristics. With the FUE Hair Transplant procedure there are restrictions on patient candidacy. FUE has an advantage over strip harvesting that it negates the need for large areas of scalp tissue to be harvested, so there is no linear incision on the back of the head and it doesn't leave a linear scar. Because individual follicles are removed, only small, punctate scars remain which are virtually not visible and any post-surgical pain and discomfort is minimized. Recovery from the Micro Grafting FUE is less than 7 days as there is no suture removal required. The major disadvantage is the increased surgical times and higher cost to the patient. It is challenging for new surgeons because the procedure is physically demanding and the learning curve to acquire the skills necessary is lengthy and tough.

There are a number of applications for Hair Transplant Surgery, like Androgenetic Alopecia, eyebrow Transplant, Frontal Hair Line Lowering or Reconstruction. If donor hair numbers from the back of the head are insufficient, it is possible to perform Body Hair Transplantation (BHT) on appropriate candidates who have available donor hair on the chest, back, shoulders, torso and/or legs. Body Hair Transplant Surgery can only be performed by the FUE harvesting method and, so, requires the skills of an experienced FUE Surgeon. However, there are several factors for a potential BHT candidate to consider prior to surgery. These include understanding the natural difference in textural characteristics between body hair and scalp hair, growth rates, and having realistic expectations about the results of BHT surgery.

In addition to the above advantages, there are number of disadvantages like hair thinning, commonly known as "shock loss", although it is temporary. Bald patches are also common, as fifty to a hundred hairs can be lost each day. Post-operative hiccups have also been seen in around 5% of transplant patients. Other side effects include swelling of areas such as the scalp and forehead. If this becomes uncomfortable, medication may ease the swelling. Additionally, the patient must be careful if their scalp starts itching, as scratching will make it worse and cause scabs to form. A moisturizer or massage shampoo may be used.