Natural Polymers as Potential Antiaging Constituents

Active pharmaceutical ingredients and pharmaceutical excipients are the core of any pharmaceutical preparation. API’s are responsible for the therapeutic activity while excipients are non-pharmacological ingredients which are used in the manufacturing of pharmaceutical preparations. As we know that some polymers have thickening property, also the water based formulations are fluid in nature therefore in order to change the rheology of such formulations various polymers are used. These polymers act by increasing the viscosity of formulations. Starch, guar gum, alginates, pectin, gelatin, agar, carrageenan, cellular derivatives are the examples of natural polymer that are used to increase the viscosity of water based formulations meant for topical application. The present review deals with the use of such natural polymers as constituents of anti-aging formulations. As is well-known that aging is a natural process in which rate of production of new cells reduces while the rate of degradation of old cells increases because the normal physiology of body changes and free radicals produced by mitochondria as a byproduct and are oxygen containing highly reactive molecules. The antiaging preparations basically neutralize the effect of free radicals and protect our cell from premature degradation. On a contrary note, the already in use synthetic polymers have adverse effect on human body as well as on environment. It is well advocated in various researches that natural polymers have no or less side effects in comparison to synthetic polymers, giving them a positive lead for incorporation to various antiaging formulations. The present review gives a deep insight on the nature of polymers used over ages, there applications and incorporation into different cosmeceuticals. It also discusses the process and mechanism of aging and the phenomenon by which cell damage can be overcome. Finally, the authors have concluded with the upcoming scenario of the use of naturally derived polymers in various skin care preparations.


Introduction
Polymers are non-pharmacological agents and use as excipients. They possess special properties and are used in site targeting, taste masking and to increase patient compliance [1].
The word 'Polymer' is derived from the Greek word and is made up of two words 'Poly' and 'meros' . Poly means 'many' and meros (Mers) mean 'parts or units of 1. All synthetic polymers are produced by chemical process so they causes adverse effect on environment as well as human being while natural polymers are produced from natural origin i.e. plants and animals and do not have any adverse effect.  [15][16][17] 2 Guar gum Guar beans Thickening properties Stabilizing properties [15,[18][19][20][21][22] 3 Alginates Present in cell wall of brown algae Thickening properties [23][24][25][26][27] 4 Pectin Present in cell wall of terrestrial plants Thickening properties Stabilizing properties [28][29][30][31][32] 5 Gelatin Obtained from animal body parts like bone and skin Used as a carrier, coating or separating agent [33][34][35][36][37] 6 Agar Present in cell wall of Algae Agarophyte Thickener, laxative, appetite suppressant [15,38]  8. Polymers are used as diluents to increase the mass for tablet compression. 9. In order to modifying drug release polymers may be coated with polymeric film. The thickness of film is 10-100 mm.
10. Various hydrophilic polymers are used for enhancing physical stability of pharmaceutical disperse system. Example: alginate, PVP, etc.
11. Drug polymer conjugates are used to alter the pharmacokinetic of drug and ultimately improving bioavailability. This strategy is also used in the treatment of cancer [8][9][10][11][12].

Aging process
Aging is a natural process in various changes occurs in normal physiological process and ultimately increases the risk of disease and death of cell, tissue and organ ( Table 1).
One of the major causes of aging process is the cellular damage that causes the shortening of DNA, leading to the process called apoptosis. Apoptosis is a process in which cell is programmed to be death in given life spam. This process is important when we realized that each cell contain genetic material and mitochondria or power house of cell. As we know that mitochondria serves as an energy generator during normal cell process and free radicals are produced a byproduct and these free radicals damage DNA and creating DNA fragments and triggers cell to apoptosis.
As time passes the more free radicals damages more DNA and fragments increase the process of cell apoptosis and our body cannot generate cells faster enough to maintain or compensate loss, so in older age we have very thin skin in comparison to young age.
In another process, the cellular down-regulation of enzymes such as superoxide dismutase, catalase and glutathione peroxide which are natural oxidative enzymes which making our antioxidant defense lesser efficient with age.
As we grow with age, the process of cellular reproduction increases and body creates non-functional cells along with functional cells, leading to rapid deterioration of the body's function. As we grow with age, the more numbers of useless cells are formed which interfere with normal cellular processes and leading to the aging process.
Free radicals: Free radicals produced by mitochondria as a byproduct and are oxygen containing highly reactive molecules with single electron in the outermost orbital that are very eager to pair up with anything else that has electrons. The life span of free radical is one-millionth of a second. Free radicals attack on cell's DNA and destroy cell prematurely and during young age out antioxidant defense system protect the cell from free radicals but as we grow this system weekend and not be able to work efficiently [48,49]. This theory demonstrates that gene of an animal or human being contains a 'program' of life span. The genetic theory of aging focuses on telomeres which are repeated units deoxyribonucleic acid and are present at the end of chromosome. The number of repeats in a telomere defines the life span of a cell, and multiple repeats are lost when each time a cell divides. When telomere has been reduced to a certain size, the cell reaches at a stage where it is prevented from further dividing, at this stage cell die.

Non-genetic cellular theory
According to this theory accumulation of harmful substance in the cells lead to aging process. Lipofuscin a dark colored insoluble substance that is accumulates day to day. This cellular garbage or cellular waste interferes with the physiology of cells and ultimately lead to death of the cell.

Error theory
Sometime during RNA transmission process a mutant protein or enzyme is produced which is not the exact same copy of original then it is not be able to work well in maintaining life, as a result cell grows and die. As we know that RNA are unstable molecules and formed continuously while DNA are stable molecules and maintained throughout the lifespan of cell and tissue.

Wear and tear theory
Changes in the internal and external environment of the cell cause cell damage and cell will not work their function efficiently. As time passes, changes in the more numbers of the cell functioning lead to change the normal physiology of body and lead to aging and death.

Cross linkage theory
As time passes deoxyribonucleic acid, different molecules and structural molecules develop a cross-linking with each other. These unwanted links/bonding decrease the mobility and elasticity of proteins and other molecules as a result molecule will not work efficiently. This cellular damage stick surround and can cause problems and cross linking appears when weakened immune system is unable to clean up the unwanted glucose in the blood. These sugar molecules react with adjacent neighbor and can cause cross-linking and lead to formation of free radicals. Immune system protect our body from different pathogens, disease, etc. they act by producing antibody against antigen and they also act engulfing and digest foreign cell by phagocytosis.
As time passes and we get older out body losses the ability to differentiate between own cells and foreign material and then immune system sometime destroying own cells along with foreign particles.

Oxidative damage theory
Denham Harman proposed free radical theory of aging in 1950s and according to this theory oxygen free radicals formed during normal metabolic process just because of lot of oxidative damage to macromolecules. This theory is further modified and a new theory came in existence that is 'Oxidative Stress Theory of Aging' . According to this theory oxygen species like peroxide and aldehyde are not technically free radicals but they play an important role in oxidative damage to cell. As age passes the imbalance between proxidant and antioxidant leads to an accumulation of oxidative damage in variety of macromolecules and cause failure of normal cellular process and leading to aging [49,50].

Topical anti-aging agent
Antioxidant and cell regulators are the main agents which are used for antiaging action. Antioxidants such as ascorbic acid, polyphenols and flavonoids reduces the collagen degradation by reducing the concentration of free radicals, while cell regulators (retinol, peptide, growth regulators) affect the collagen metabolism and stimulate collagen production.
Ascorbic acid, tocopherol, niacinamide is low molecular weight antioxidant and they have the ability to penetrate skin. l-Ascorbic acid is water soluble photosensitive substance having anti-aging action at the concentration of 5-15% and act by inducing the production of collagen 1 and collagen 3. Several enzymes are also important in the production of collagen.
The combination of vitamin E and vitamin C is more effective in comparison to individual effect of vitamin E and vitamin C.

Niacinamide (B 3 )
Vitamin B 3 regulates the cellular physiology such as metabolism and regeneration and is effective as anti-aging agent at concentration 5%. A result comes from clinical study that elasticity, erythema and pigmentation of study were improved after topical application for 3 months.

α-Tocopherol (vitamin-E)
Vitamin E is used in the cosmetic cream because of its anti-inflammatory and anti-proliferative activity at the concentration 2-20%. Vitamin E smoothing the skin and act by increasing the cell's ability to maintain humidity and accelerate the process of epithelialization and protect the skin from sunlight but it is not as such effective as combination of vitamin C and vitamin B 3. Some botanicals such as isoflavones from soya and topical application of green tea polyphenols decreases the number of langerhans cells and reduces deoxyribonucleic acid damage in skin.
Cell regulators such as retinol derivatives (retinaldehyde and tretinoin), polypeptides and botanicals act by affective collagen metabolism and increase the production of collagen and elastic fibers.
Retinol and its derivative such as retinaldehyde and tretinoin are antioxidant and have anti-aging action. They stimulate the synthesis of collagen and reduce the expression of matrixmetaloproteinase-1. Retinol is most commonly used topical cosmetic preparation in comparison to tretinoin because it causes less irritation.
Tretinoin is the nonaromatic retinoid of the first generation and is approved by United States for topical application as an anti-aging treatment at the concentration of 0.05%. It is used for the treatment of wrinkles, ultra violet induced skin aging, pigmentation and loss of skin elasticity.

Types of antioxidant
Three types of anti-oxidant found in nature i.e. phytochemicals, vitamins and enzymes. Potent anti-oxidants are found in plants because plants are exposed to ultra violet light throughout of the day. Plants generate high quantity of free radicals but they do not cause cellular damage, because they are protected by naturally occurring anti-oxidant defense system.

Anti-oxidant enzymes
These enzymes are basically antioxidant and are synthesized in human body when eat proteins and minerals as our daily diet. The examples of these enzymes are superoxide dismutase, glutathione peroxide, glutathione reductase and catalases. They require co-factors such as iron, copper, selenium, magnesium and zinc for anti-oxidant activity.

Anti-oxidant vitamins
Human body is not able to synthesize or produce these anti-oxidant vitamins naturally but they require for maintaining normal physiology and health, so we take these vitamin in our daily diet. Retinol, l-ascorbic acid, α-tocopherol, folic acid and beta-carotene are the examples of anti-oxidant vitamins.
Retinol is important in tissue repair, for eye health, for improving immune system as well as for improving cholesterol level. l-Ascorbic acid protects our skin from ultra violet light damage and it stimulates immune system by providing resistance from infection and helps in regulating cholesterol level.
α-Tocopherol play an important role in maintaining health of blood vessels and it also improve the skin condition by protect the cell's membrane. Folic acid is useful in the process of erythropoiesis.
Various phytochemicals such as carotenoid provide protection against singlet oxygen and free radicals. These carotenoids are found in orange-colored vegetables like carrot as well as in dark green vegetables like kale, etc.

Anti-oxidant phytochemicals
Phytochemicals are natural anti-oxidant and they are found in plants and used by plants in order to protect themselves from free radicals. Phytochemicals are naturally fount in whole foods like whole grains, fruits and vegetables. Phytochemicals may be dividing into following category.

Natural anti-oxidant in human body
As we know that free radicals attack on DNA and interferes with normal physiology of cell and to protect DNA from these attacks a series of defense mechanism is developed by body. Anti-oxidant act at different levels and by different mechanism in the defense system such as preventive mechanism, radical scavenging and repair and adaptation ( Table 2)

Second line of defense
In second line of defense include retinol, α-tocopherol, uric acid, bilirubin, albumin and thiols. This anti-oxidant scavenges the active radicals and breaks the chain propagation reaction and suppresses chain initiation.

Third line of defense
Third line of defense includes proteolytic enzymes, proteinases and peptidases present in the cytosols and in the mitochondria of mammalian cells, etc. they act by repair deoxyribonucleic acid.

Fourth line of defense
Fourth line of defense include adaptation, in this signals for the production and reaction of free radicals induce the formation of antioxidant and they also transport the suitable antioxidant to the right place.
Various types of natural antioxidant fount in nature and they are differ in their specifications, mechanism of action and their composition, etc. [55][56][57][58][59]

Enzymes
These enzymes act as antioxidant and act by converting reactive oxygen species and reactive nitrogen species into stable compound and is important in the repairing of damaged DNA, Proteins and oxidized peroxides.

Superoxide dismutase (SOD)
Superoxide dismutase catalyzes the breakdown of superoxide anion into hydrogen peroxide and oxygen. These enzymes are present in aerobic cells as well as in extra cellular fluids. In plants, superoxide dismutase are present in chloroplast, peroxisomes and apoplast in cytosol, while in human body superoxide dismutase-1 present in cytoplasm and superoxide dismutase-2 in mitochondria and superoxide dismutase-3 in extracellular [59][60][61][62][63][64].

Catalase
Catalase is an enzyme and present in almost all living organism which are exposed to oxygen and its function is to catalyze the decomposition of hydrogen peroxide into water and oxygen. As we know that hydrogen peroxide is harmful substance and produced by various metabolic processes and to prevent damage from hydrogen peroxide, catalase converts the hydrogen peroxide into water and oxygen [65].

Glutathione
Glutathione is a cysteine containing peptide found naturally in aerobic organism and it is not required in daily diet because it is synthesized in cells from amino acids [66]. Thiol group in its cysteine moiety of glutathione is responsible for antioxidant activity. Glutathione is one of the most important cellular antioxidant enzymes which present in high concentration and play an important role in maintain redox state of cell [67].

High molecular weight compounds
Metal catalyzed free radicals production is restricted by few high molecular weight compounds like albumin, transferrin, ceruplasmin, etc. [68]

Low molecular weight compound
Low molecular weight compounds like Tocopherol, quinines, bilirubin are lipid soluble antioxidant while ascorbic acid, uric acid are water soluble antioxidants [69].

Minerals
Selenium, copper, manganese, zinc are mineral antioxidants. Copper shows antioxidant activity through SOD while zinc is necessary for normal growth and reproduction of body [70].

Vitamins
Vitamins re organic molecules and essential for normal growth of body and helpful in maintain normal physiology of body. Retinol, ascorbic acid and tocopherol are popular antioxidant agent [71,72].

Ascorbic acid
l-Ascorbic acid or vitamin-C is a monosaccharide antioxidant found in animals as well as in plants e.g., citrus fruits. Human body is not able to synthesize vitamin-C, so it is taken in food as regular diet. Inside the cell, it is maintained in its reduced form by reacting with glutathione, which further catalyzed by protein disulfide, glutaredoxins and isomerase [73].
Actually vitamin-C is a reducing agent and can reduce, thereby neutralize reactive oxygen species, such as hydrogen peroxide [74].

Tocopherol and tocotrienols
Vitamin E is fat soluble vitamin with antioxidant properties, and a collective set of eight related tocopherol and tocotrienols [75]. α-Tocopherol is one of the most important lipid soluble antioxidant and it protect the cell membrane from oxidant by reacting with lipid radicals which are formed in lipid peroxide chain reaction [76]. These free radical intermediates are then removed and prevents the propagation reaction from continuing. In this reaction oxidized α-tocopherol radicals are formed which recycled back to the active reduced form through reduction reaction by other antioxidants such as vitamin-A, etc. [77]

Melatonin
Melatonin is produced by the pineal gland and have bleaching action on skin pigment i.e. melanin. Melatonin is used as a protective agent against various processes and agents which damage the tissue via free radicals. Melatonin is found in all living organism. As we know that melatonin is a naturally occurring hormone and chemically is N-acetyl-5-methoxytryptamine [78] and found in animals and in algae [79].
Melatonin is highly lipophilic in nature and having an ability to cross various barriers like cell membrane as well as highly selective barriers like BBB [80]. Melatonin also known as 'suicidal anti-oxidant' because it cannot be recycled when it reduced to its former state [81].

External anti-oxidant
As we know that our body is programmed to generate own antioxidants to protect life but body is also designed to fight inflammation, disease and toxins naturally. In order to support these internal antioxidant systems we also take some external antioxidant in our diet as regular meal. External antioxidant include vitamins and some specific food products, etc.
Peoples who eats fresh fruits and vegetables regularly have lower risk of health loss. Some heart disease is also prevented by taking tocopherol as nutritional supplement [82].
Nutritional supplement include specific antioxidant chemicals like polyphenol, resveratrol and some other minerals and vitamins. Spices like turmeric, coriander, cumin, fennel also have medicinal properties. Food and part of foods which provide medicinal benefit known as "Nutraceuticals". These nutraceuticals also helpful in maintaining normal physiology of body [83] ( Maintain moisture content in skin as well as regulate cell regeneration [88] 9 N-acetyl glucosamine Shells of crabs, shitake mushroom, shark cartilage, dumontiaceae (red Japanese algae) Act by improving skin moisturization [89] 10 Peptides Milk, eggs, grain, soybean etc.
It act by increasing collagen production and inhibit the breakdown of collagen [90]  12. Role of polymers in anti-aging preparations 1. As thickeners 2. As structuring agent 3. In hair products 4. As delivery system

As thickeners
As we know that some polymers have thickening property and water based formulations are fluid in nature and in order to change the rheology of these formulations these polymers are used. These polymers are used to increase the viscosity of these formulations.

Natural thickeners
Starch, guar gum, alginates, pectin, gelatin, agar, carrageenan, cellular derivatives are the examples of natural polymer that are used to increase the viscosity of water based formulations.

Synthetic thickeners
Polyacrylate derivatives, polyacrylamide are most commonly used synthetic polymers in cosmetic industry.

Role of natural polymers as thickening agent in antiaging preparations
Thickening agent or thickener is a substance which are used to increase the viscosity of fluid.

Xanthan gum
Xanthan is a polymer and consist of a repeating units of pentasaccharides (two d-glucopyranosyl unit, two d-mannopyranosyl unit and one d-glucopyranosyluronic unit). It is a free flowing powder and gives a viscous solution in hot as well as in cold water even at low concentration. It is widely used in cosmetic, toothpaste as well as in antiaging preparations.

Pectin
Pectin is obtained from various citrus peels like orange peel and other peels of various family but citrus peels have highest concentration i.e. 20-30%. In pharmaceutical industry pectin is used as binding agent in tablets as well as used to increasing the viscosity of fluids.

Carrageenan
It is obtained from the various species of red seaweed of class Rhodophyceae like Chondrus crispus, Eucheuma cottonii.
Carrageenan is used in the manufacturing of shells of soft and hard gel capsules as substitution of gelatin. Carrageenan is also used to increase the viscosity of formulations which are liquid in nature.

Guar gum
The botanical source of guar gum is Cyamopsis tetragonoloba. The composition of guar gum is sugar galactose and mannose. It is used as stabilizer, thickening agent in liquid formulation and as a binder and disintegrant in solid dosage form i.e. tablet [1].

Structuring agent
In order to add rigidity natural and synthetic waxes, lanolin, long-chain fatty alcohols and triglycerides are used. Poly α olefin is used in the preparation of lip products. Glycol stearates is used as opacifier, which gives a pearlizing affect.

In hair products
Cationic polymers are used in hair products since hair is negatively charged.

Natural polymers in hair product
Polysaccharides (starch and cellular derivatives), natural gums and hydrolyzed proteins are used as natural polymer in hair product.

Synthetic polymers in hair product
Silicones, polyurethanes, poly vinyl amides, poly vinyl pyrrolidone and acetate polyurethanes are the examples of synthetic polymers.

Delivery system
Sometime polymers are used as a carrier to deliver active pharmaceutical agent i.e. antioxidant. Natural antioxidant include ascorbic acid, tocopherols, grape seed extract along with synthetic extract like butylated hydroxyl anisole/butyl hydroxyl toluene. E.g. polyanhydride ester is used as a carrier to deliver salicylic acid (anti-acne agent) [91,92] (Table 3).

Conclusion
The attitude and lifestyle of society changes from last decades and they are more conscious for their health and appearance due to this change various new antiaging formulations are introduced in market. Antiaging formulations generally contain antioxidants and vitamins like vitamin-E (tocopherol), ascorbic acid, etc. The cosmetic industry is one the growing industries in the India, not even in India but throughout the world. Various new formulations like creams, face washes, face pack, emulsions are introduced day by day. As we know that synthetic chemicals show various side effects on human body, due to this peoples prefer polyherbal  © 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
formulations which contain antioxidant along with natural polymers. Polymer in antiaging formulations serve as a thickening agent like guar gum, pectin etc. and as a structuring agents. Polymers non-pharmacological agents and used as an ingredient in various formulations. Natural and synthetic both polymers are used in pharmaceutical industry but because of the side effects of synthetic polymers, the attitude of the people changed and they prefer natural polymers containing antiaging formulations. The demand of natural polymer containing antiaging agents increases day by day, this change causes change in manufacturer to use herbal polymers instead of synthetic polymers.