INTRODUCTION:

Liposomes term was discovered by Paul Ehrlich in 1906 as a targeted delivery. Since first being described by English haematologist Alec Bangham, in 1961¹. The first artificial lipid vesicles called liposomes and the first liposomal cosmetic product introduced into the commercial market was the capture anti-ageing cream by firm Christian Dior in 1986. Since then the active research in the field of liposomes have been carried out and their applications are now established in various areas, such as drug, cosmetics, and gene delivery etc².

Liposomes are sphere-shaped vesicle and mainly consists of phosphor lipid bilayer encircling a polar core³ where the water-soluble pharmaceutical active ingredients are encapsulated (i.e. central core) hydrophilic heads while the hydrophobic part consistingof two fatty acid chains, can incorporate hydrophobic pharmaceutical ingredients^4,5. The encapsulation process in the pharmaceutical industry is utilized in fragrances to yield a sustained release, to protect volatile component present in the formulation as well as providing a delayed release in some products^6,7. It hasbeen estimated that 50% of the US public are aware of anti-ageing therapies⁸, and 2000, sales of topical anti-ageing preparations and herbal product is the large proportion of this market⁹. Topical application of anti-ageing formulations has been adopted as an important strategy as they serve as a non-invasive alternative to slow the effects of ageing on the skin andthe stratum corneum or horny layer has been identified as the principlebarrier forpenetration of most drugs and liposome based formulations have been found to extremely promising for topical delivery¹⁰.

Liposome:

Liposomes are spherical colloidal, vesicles in which their central aqueous section is surrounded by one or more of a bilayer membrane (Lamella) that is frequently enclosed by aquatic environments which have uncharged positively, negatively or 2 oppositely charged polar heads and in the formation of membrane natural or synthetic phospholipids in which adding cholesterol will increase their stability and lecithin is an another phospholipids which mostly extracted from natural source such as egg, soya bean^11,12. They can vary in size from 15 nm to several microns. In the last 30 years, the application of liposome has been expanded from drug delivery to the cosmetic field^13.

Figure 1: Structure of liposomes

Types of Cosmetic Liposomes:

Table 1: Discussion of types of liposomes used in cosmetic preparation ^{14,15,16,17,18,19,20}

Cosmetics Liposomes	Descriptions
Transferosomes	They are highly deformable, reactive and efficient liposomes applied until now direct transdermal drug delivery and its dimension (300-200nm) so they can easily penetrate the skin and prepared by phospholipids, cholesterol with the addition of some surfactants.
Navasomes	They are non-phospholipid oligolamellar lipid vesicles of 0.1-1.0 microns that are a variety of liposome or modified niosomes and in cosmetic, they used as a sustain released and improve the texture of cosmetic.
Marinosome	These types are made from marine lipid extract that contains a high rate of Eicosapentaenoic acid Docosahexaenoic acid that is omega-3 polyunsaturated fatty acid and they heal the skin’s inflammatory problems.
Ultrasome	They are a unique category of liposomes which are formed by entrapment of the endonuclease extracted from micrococcus luteus. They help to detect UV radiation harm to the skin and increase the speed of treatment 4 times.
Photosomes	They act by releasing photolysis enzymes extracted from the marine plant. They are extensively used in sunscreens which prevents light from damageingcell’s DNA and reduce the risk of cancer.
Ethosomes	These are multilayered liposomes used in cosmeceuticals delivery to enhance the bioavailability.
Nanosome	They are very small liposomes formed from highly pure phosphatidylcholine in a low nanometer size range. They applied as an anti-ageing serum.
Glycerosome	They are modified liposomes containing glycerol in addition to phospholipids. They used to deliver cosmeceutical active ingredient to the skin with high performance, healing, beautification properties and they contain quercetin and its size 80-110nm shows skin defensive activity
Oleosome	They are natural liposomes and a reservoir of oil, vitamins, and pigments. They are made up of sea buckthorn fruits-flesh demonstrated high stability and antioxidant properties.

Mechanism action of liposome:

The activity of liposomal formulations in ageing is attributed to its occlusive action, enhanced bioavailability, protection of active ingredients, reduction of systemic absorption and reduction of side-effects. Liposomes as a carrier itself offer the advantages because lipids are well hydrated and cosmetic containing liposomes rely on this effect can reduce the dryness of the skin which is the primary cause for skin ageing.²¹

Table 2: Liposomes characterization

Assays	PH, phospholipid concentration and composition, drug concentration, cholesterol concentration
Chemical stability	Phospholipid peroxidation, phospholipid hydrolysis, cholesterol autooxidation, antioxidant degradation
Physical stability	Vesicle size distribution, number of bilayers, encapsulation efficiency, dilution-dependent drug release, electrical surface potential
Biological characterization	Sterility, pyrogenicity, animal toxicity

Skin ageing:

Ageing is defined as a progressive deterioration of physiological function in the organism, eventually leading to senseless and death.²²The sign of ageing includes fine lines and wrinkles, alterations in skin pigmentation, and thinner appearance of the skin due to epidermal and dermal atrophy²³

(A) (B)

Figure 2: Structure of (a) Skin ageing (b) Anti-ageing

Anti-ageing:

Increasing the expectancy of median life as well as improving the quality of life and preventing the consequences of ageing are receiving great attention in research at present²⁴ Everlasting youth has always interested humankind, now the goal of youth has changed to increase the duration of healthy lifestyle of an individual rather than increasing the life span only.²⁵ Cosmeceutical formulations, researchers and pharmacists are paying extra attention to the ageing consequencesin the skin, trying to find a cost-effective solution to a difficult problem. Estimates show that 2 billion dollars were spent on anti-ageing product in the United States in 2000.²⁶

Types of Skin ageing:

Ageing can be divided into two categories: Intrinsic or chronological ageing and extrinsic or prematureageing .²⁷

Fig.3: Mechanism of Ageing

Intrinsic Ageing:

Intrinsic ageing is a natural occurrence in which numerous simultaneous mechanisms occur. Dead skin cells do not shed as quickly, and the turnover of new skin cells maydecrease slightly. The sign of intrinsic ageing are as follows; Fine wrinkles, thin and transparent skin, loss of underlying fat leading to hollowed cheeks and eye sockets, bones shrink, hair loss ridges develop.²⁸

Extrinsic Ageing:

Extrinsic ageing is caused by exogenous origin, i.e. smoking, poor nutrition, solar exposure. These factors are responsible for premature ageing of the skin. Loss in tone and elasticity is observed along with increased skin fragility, benignlesions.²⁹

(A)

(B)

Fig.4: Clinical appearance of intrinsic (a) and extrinsic (b) ageingof skin

Antioxidants used in anti-ageing products:

Antioxidants play an important role in the prevention of ageing. Many antioxidants are now available in oral and topical preparations. Combination of various antioxidants may have synergistic effects. Various antioxidant actives used in anti-ageing formulations are as follows.³⁰

Retinol:

Vitamin A has antioxidant activity it is used to treat the skin ageing and it also has a nutritive value which enhanced the skin activity when applied topically and also helpful for eyes.³¹

Alpha Lipoic acid:

It is the most potent antioxidant in the market today. It enhanced the skin cell metabolism and helps repairs aged skin and restore the level of glutathione, a protective antioxidant, and detoxification compound, to near normal.³²

Ascorbic acid:

Vitamin c is a highly water-soluble, sugar- like, low molecular weight ketolactone. It is a proven anti-wrinkle treatment that works as both a free radical scavenger and it enhanced the collagen reduction.³³

Lycopene:

It is a bright red carotenoid antioxidant and quenchers for free radicals.³⁴

Tocopherol:

Vitamin E is a lipid-soluble antioxidant that is present in the skin and found in various food such as vegetables, seeds, and meat. It makes skin repair itself and epidermis is likely less dry out³⁵

Table 4: Green extract used in loaded cream formation ^{36, 37}

Botanical name	Family	Part used	Nature of extract	Antioxidant	Nature of cream	Oil phase	Emulsifier
Acacia	Mimosaceae	Bark	Ethanol	Phlobatannin	SimpleW/Ocream	Paraffin oil	ABIL EM 90
Benincasa hispida	Cucurbitaceae	Fruit	Petroleum ether	Caffeic acid	Simple W/O cream	Cetyl alcohol	Polysorbate
Camellia sinensis	Theaceae	Leaves	Ethanol	Epigallocatechin gallate	Simple W/O cream	Paraffin oil	AMBIL EM 90
Punicagranatum	Punicaceae	Seeds	Ethanol	Ellagic acid	Simple W/O	Paraffin oil	ABIL EM 90
Crocus sativum	Iridaceae	Flower	Ethanol	Lycopene	Simple W/O	Paraffin oil	ABIL EM 90

Table 4: Commonly used plant parts and its active constituents in anti-ageing formulations ^38,^{39, 40}

Source	Common name	Plant part used in anti-ageing	Action	Active constituents
Anethumgraveolens	Dill	Seed oil extract	Detoxifying enzyme, boost elasticity, Anti-ageing	Carvone, limonene, cineole, dillapiol
Aloe vera	Aloe	Aloe vera gel	Moisturizing, vitamin E, A and C and production of collagen, Anti-ageing	Beta-carotene, Aloin, chrisophanic acid, aloe amodine
Ananacomosus	Pineapple	Pulp extract	Antioxidant, reduce wrinkle, Anti-ageing	Bromelin, Ascorbic acid, Retinol.
Arctostaphylosuva-ursi	Bearberry	Leaf extract	Brightening skin, Anti-ageing	Arbutin, quercitin, hyperin
Arctiumlappa	Burdock	Fruit extract	Treat acne, Anti-ageing	Caffeylquinic
Artemisia vulgaris	Mugwort	Leaf extract	Antioxidant and vitamin E, Anti-ageing	Cieole, thujone
Aspalathuslinearis	Rooibos tea plant	Leaf extract	Antioxidant, Anti-ageing	Benzoic acid, cinnamic acid
Tamarind indica	Indian date	Seed oil	Antioxidant, anti-ageing	Malic acid, pectin, safrole
Carica papaya	Papaya	Seed extract	Antioxidant, anti-ageing	Papain, ascorbic acid, quimiopapain
Crocus sativum	Saffron	Flower part	Anti-ageing, Anti-ageing	Safranal, crocetin, crocin
Curcurbita pepo	Pumpkin	Seed oil	Vitamin c, Antioxidant, Anti-ageing	Cucurbioside A, Lariciresinol
Citrus limon	Lemon	Fruit extract, seed oil	Antioxidant, anti-ageing	Linalool, geraniol, linalyl acetate
Citrus aurantium	Orange	Orange stem extract	Anti-wrinkle, anti-photo-ageingagent	Carveol, carvone
Cinnamomumcamphora	Camphor	Stem extract oil	Anti-ageing, anti-wrinkle	Cineole, butenoic acid, safrole
Rubusfruticosus	Blackberry	Leaf extract	Anti-aging, anti-wrinkle	Gallic acid, quercetin, tocopherol
Olea europaea	Olive	Leaf extract	Anti-ageing	Oleic acid, tyrosol
Juglans regia	Walnut	Fruit oil extract	Anti-ageing, anti-oxidant	Ferulic acid, vanillic acid, coumaric acid
Moringa oleifera	Drumstick	Moringa oil	Anti-ageing, Antioxidant	NiazininA, niazimicin A, nonanal
Linumusitatissimum	Linseed	Flaxseed oil	Anti-ageing, Antioxidant, Omeg-3 fatty acid	Linamarin, linustatin, lotaustralin
Salvia hispanica	Chia	Chia oil	Anti-ageing	Linoleic acid, stearic acid
Centellaasciatica	Gotu kola	Leaf extract	Increase collagen, anti-ageing, antioxidant	Asiatic acid, madecassic acid
PunicaGranatum	Pomegranate	Seed oil	Vitamin C, Anti-ageing	Ellagic acid, punicalagins
Thymus Vulgaris	Ajwain	Thymol seed oil	Antioxidants, anti-ageing	p-cymene, linalool, myrcene
TrigonellafoenumGraecum	Fenugreek	Seed oil	Anti-ageing	Cinnamic acid, scopoletin
Piper cubeba	Cubeb	Seed oil	Anti-aging	Cubebene, germacrene
Indian gooseberry	Amla	Fruit extract	Antioxidant, Anti-ageing	Ascorbic acid, chebulinic acid
Cocos nucifera	Coconut	Kernel extract	Anti-wrinkles, Anti-aging	Lauric acid, poleic acid, capric acid
Nigella sativa	Cumin	Seed oil	Anti-wrinkles, Anti-ageing	Myrcene, cumin aldehyde, p-cymene
Rosa rubiginose	Rose	Flower extract	Anti-ageing	Citronellol, geraniol. Linalool
Azadiractaindica	Neem	Seed oil	Antioxidant, Anti-ageing	Nimbin, azadirachin
Mangiferaindica	Mango	Seed oil	Collagen production, Anti-ageing	Palmitic, linoleic acid, behenic
Ocimumtenuiflorum	Tulsi	Leaf extract	Antioxidant,Anti-ageing	Rosmarinic acid, eugenol, oleanolic acid
Cymbopogon	Lemon grass	Leaf extract	Antioxidant, Anti-ageing	Myrcene, geraniol,
Lagenariasiceraria	Laukidf	Seed oil	Anti-wrinkle, Antiageingj

Table 5: Equipment used for in vivo characterization of botanical cream^41,42

S. No.	Equipment	Purpose of use
1	Mexameter	Erythema analysis transepidermal
2	Tewameter	Water loss evaluation
3	Evaporimeter	Barrier function test
4	Corneometer	Detection of skin hydration
5	Sebumeter	Assessment of skin surface sebum
6	Visiometer	Wrinkle test
7	Cutometer	Measurement of skin elasticity

Table 6: List of somearticles and years and theirconclusion

Journals name	Publication Year	Title	Author references	Conclusion
Pharmaceutics	2019	Liposomal Vitamin D3 as an Anti-ageingagent for the Skin	Ye Bi, Hongxi Xia, Lianlian Li, Robert J. Lee, Jing Xie, Zongyu Liu, ZhidongQiu and LeshengTeng Department of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, Jilin, China	Excessive exposure to sunlight causes skin photoaging, VD3 was found to have a good protective effect from UV radiation and photoaging. Of course, there are still some remaining issues to be overcome, such as stability and skin uptake of VD3. In 1987, Christian Dior launched the first liposomes cosmetic “Capture”. Since then, this class of cosmetic has received positive attention, finally, VD3 liposomes could significantly improve skin appearance and protect from photoaging the skincare field.^43,44
Noval Approaches in Drug Designing & Development	2018	Isoflavones-Based Liposome Formulations as Anti-ageingfor Skincare	Sophie Hollmerus, SakibYousaf, Yamir Islam, Iftikhar Khan, School of Pharmacy and biomolecular Science, Liverpool John Moores University, UK	Isoflavones based modified liposomes help to protect skin from ageingand provides antioxidant, prevent from loss of moisture and enhance the glow of theskin^{45, 46, 47, 48}
International Journal of Molecular Sciences	2017	Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils	Tzu-Kai, Lily Zhong, and Juan Luis Santiago, Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University	Plant oil has so many effects on the skin it provides the antioxidants to the body also work as anti-ageingand heal the body and develop dermatological treatments.^{49, 50,51,52}
Journal of Skin and Stem Cell	2016	Liposomes in Cosmetics	Hamid Reza Ahmadi Astiani, ParisaBishe, Naser-AldinLashgari, Department of Basic Sciences, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, IR Iran	Liposomes play an important in the topical delivery which enhanced the beauty and provide the stability of the cosmetic and release of active principal to the targeted site.^53,54
Hindawi	2015	Recent Advances in Liposomal Drug Delivery	VijaykumarNekkanti and Sandeep Kalepu, College of Pharmaceutical Sciences, Western University of Health Sciences Pomona, CA, USA.	Liposomes have been used in many pharmaceutical applications. Now a time by the help of liposomal delivery we promote the natural things and to fulfil the human needs so we need to developdifferent formulation against ageing.^55,56,57
Journal of AgeingScience	2014	Promotional of the Stability of Liposomal formulations for Anti-ageingTherapy	Hong Van Luong, Vice-director, Viettnam Military University, Vietnam	Lycopene is an essential antioxidant for the prevention of several pathological conditions so lycopene liposomal formulation is a new technique to improve the stability of formulation.^58,59,60
International Journal of Drug Development and Research	2013	Liposomal drug delivery system	Sandeep kalepu, SunilkumarKTDepartment of Pharmaceutical Technology, Shri Vishnu College of Pharmacy, Andhra Pradesh, India	Drugs encapsulated in liposomes can have a significantly altered pharmacokinetics, the efficacy of the liposomal formulationdepends on its ability to deliver the drug molecular to the targeted sites.^61,62
International Journal of Pharmaceutics and chemical sciences	2012	Liposomes: As a Topical Drug Delivery System	Patel Meghana C, Patel Hardik, Mehsana Urban Bank Institute of Biosciences, Ganpat University, Kherva, Gujarat, India.	Liposomes are interesting as a drug carrier and its formulation provide sustained, enhanced level of deeper strata of the skin and enhanced the systemic absorption.^63,64
International general of green pharmacy	2011	Antioxidants in skin ageing-Future of dermatology	Shamika M. Salavkar, Rashmi A. Tamanekar, Rajani B. Athawale, Department of Pharmaceutics. C.U. Shah College of Pharmacy, S.N.D.T Women’s University, Mumbai	We all can truly “look as young as we feel” by applying topical antioxidants. It may increase the life long and enhanced the beauty and free from disease condition.^65,66
Act Clin Croat	2010	Local therapy as basic anti-ageingprevention	NeviaDelalle-Lozica, Dermalife Polyclinic for Dermatology and Venereology, Zagreb, Croatia	Skin is the largest organ of the body, is the organ in which changes associated which ageingare most visible. By the application of the natural anti-ageingproduct, we can feel the relief against ageing.^67,68

CONCLUSION:

The universal healing power and regaining the health by natural therapy while using one concept i.e. liposomal based drug delivery system against ageing. It is the new weapon of treatment evolved from recognition of a link between nutrition and pharmaceuticals which are beneficial to overall the health. It is advanced drug delivery technology utilized to present the drug to the desired body site for drug release and absorption and prevent from ageing. Today ageing is a most common disease which causes an abnormality of bodily structure or function due to intrinsic or extrinsic factor and can treat by using food or part of food in a modified therapy which is beneficial to overall the health. Now a newand natural therapy is available in a liposomal form that heals and treats the ageing process and inhibit the ageing and supply antioxidants in the form of known term anti-ageing.

CONFLICTS OF INTERESTS:

The authors declare no conflict of interest.

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Received on 25.12.2019 Modified on 20.01.2020

Res. J. Pharmacology and Pharmacodynamics.2020; 12(1):05-11.

DOI: 10.5958/2321-5836.2020.00002.6