INTRODUCTION:

Liposomes in skincare:

Liposomes are one of the delivery systems which helps in the absorption of cosmetic ingredient to the skin. Liposomes also improve stability and skin hydration by surface adhesiveness, improve dermal bioavailability, and support skin cell regeneration and skin targeting. In pharmaceutics, we have a vast area for designing different dosage forms in order to deliver the active pharmaceutical ingredient to its site of action. However, in cosmetics, since the skin is the first defensive barrier against external factors and prevents many substances from entering the underlying layers or systemic circulation, there are some limitations to delivering the active ingredient to the target site. This can be overcome by the role of liposomes in cosmetics¹.

Liposomes are capable of serving as both carriers for cosmeceutical ingredients and as active ingredients in and of themselves. Empty liposomes can interact strongly with skin lipids, proteins, and carbohydrates when skin is eczematized or damaged from a lack of moisture, helping the skin to restore to its natural state and enabling the stratum corneum to effectively carry out its protective job².

Facilitate the Penetration:

The skin plays a crucial role in safeguarding the body as it is the largest organ and covers the majority of the surface area. The epidermis, which is the top layer of skin, is followed by the dermis, which contains connective tissue, sweat glands, and hair follicles, and the hypodermis, which is made up of adipose tissue and connective tissue. The stratum corneum, the outermost layer of the epidermis, performs the crucial function of a skin barrier because of its high lipophilicity profile and strong cellular cohesion². A molecule needs to have specific physicochemical characteristics in order to easily permeate the stratum corneum, such as being light in weight, water and oil soluble with an intermediate distribution coefficient, and having a low melting point ³. Only a small number of compounds have these optimal qualities, while the majority of others fail to cross the epidermal barrier and do not deliver an appropriate concentration of active chemicals to the site of action. As a result, the desired topical or systemic action won't be experienced. Utilising liposomes as carriers for active dermatological and cosmeceutical compounds may be useful in overcoming this restriction and help the ingredients cross the skin ². In comparison to conventional dose forms, liposomes greatly facilitate penetration inside the horny layer due to their small size and structural resemblance to skin in terms of lipid composition⁴.

Table 1: Key Benefits of Liposomes in Cosmetic Formulations.

Benefits	Description
Enhanced Penetration	Liposomes facilitate deeper delivery of active ingredients into the skin.
Improved Stability	Sensitive ingredients like retinol are protected from degradation.
Hydration Support	Liposomes help maintain skin moisture, leading to improve skin texture.
Bioavailability	Liposomes increase the availability of active ingredients at the site of action.
Protection from UV	Certain liposomal formulations protect the skin from UV induced damage.

Liposomes used in cosmetic applications:

Phospholipids, the same substances that make up the cell membrane, are used to create the tiny bubbles known as liposomes. These bubbles can aid in delivering active substances deep within the skin, where they are most required, when utilised in skincare products. Vitamins, antioxidants, and other nutrients needed for healthy skin are frequently delivered via liposomes. These chemicals are more effectively able to permeate the skin and deliver their advantages when they are enclosed in liposomes. There are many different kinds of liposomes, and each one has advantages that can be used in skin care products. For instance, some liposomes are made to release their contents gradually over time, but others are made to rupture when they come into contact with the skin, releasing a large quantity of active substances at once. Every form of liposome utilised has the same objective: to assist you in achieving healthy, attractive skin. The capacity of skin care to distribute active chemicals straight to the skin is among its most challenging features. Pharmaceutical companies frequently use liposomes, which are spheres with phospholipid bilayers around internal water compartments. The lipids in the mortar of a corneocyte allow molecules carrying lipoic nutrients to diffuse through them. Drugs and protein can be delivered through liposomes, which are used in many different applications. Liposomes may be produced on a massive scale, are non-toxic, and have a wide range of uses. In immunology, they make good protein antigen carriers since they can hold a lot of antigens. They are utilised to move cosmetics components to the deeper epidermal layers. Through DNA skincare, liposomes carry the active chemicals deeper into the skin. Among the lipids that make up liposomes include phospholipids, phosphatidylethanolamines, and emulsifiers. You cannot tell if a product contains them unless it is specifically stated on the packaging. Liposomes also help to improve the stability of active ingredients, improve skin hydration through surface adhesiveness, increase dermal bioavailability, and protect skin cells from external stressors such as sweat and sunburn.

Liposomes, which are small artificial vesicles with a spherical shape, are made from cholesterol and natural phospholipids. Liposomes have the characteristics of being large, hydrophobic, and hygroscopic, making them excellent systems for drug delivery.

Liposomes, or tiny particles in a skin cream, are said to transport many of the substances in the cream deep into the skin, smoothing and firming the skin. A liposome is a spherical structure made up of several phospholipid bilayers, which resemble cell membranes in structure. Liposomes, one of the delivery vehicles, aid in the skin absorption of cosmetic ingredients. Liposomes improve the stability of active ingredients, aid in skin hydration, increase bioavailable dermal tissue and protect skin cells from external stressors such as sweat and the sun. They are both bio-degradable and non-toxic, making them ideal for your skin and a great alternative to cosmetics. Liposomes enable the body to infiltrate deeper layers of skin and deliver nutrients to the skin. This type of product can help to protect the skin from signs of aging, and dry skin, and keep the skin moisturized for an extended period of time.

Liposomes are unique ingredients that are used to deliver skincare ingredients. Small, microscopic vesicles with an aqueous centre surrounded by phospholipid membranes. When retinol is encapsulated, it is encapsulated in liposomes. These tiny structures can act as conduits for active skincare ingredients to enter the most important areas of the epidermis. When retinol liposomes are applied, they are ideal for delivering the drug to the skin. Liposomes have a lot to offer in terms of physical properties and composition, but they are not the primary entry point for drugs into the skin. Liposomal retinol, according to its encapsulation, protects it from oxidation and other damage. The skin becomes more effective and durable when used in this manner. Liposomes are a great way to deliver skincare ingredients directly to the skin.

Liposomes are tiny, spherical sacs made from a phospholipid bilayer that can encapsulate and deliver drugs or other substances to cells. They are often used in cosmetics and skin care products because they can help to improve the absorption of active ingredients through the skin. While it is generally accepted that liposomes can be absorbed through the skin, there is still some debate about how effective this process is. Some studies have shown that liposomes can indeed be absorbed through the skin and that they can help to improve the delivery of active ingredients. However, other studies have not been able to confirm these findings. Overall, the evidence suggests that liposomes can be absorbed through the skin, but the extent to which this occurs is still not fully understood.

Liposomes are very commonly used in cosmetics, as they are very effective at delivering active ingredients to the skin. Liposomes are tiny spheres made of phospholipids, which are the same molecules that make up the cell membranes. This enables them to easily penetrate the skin and deliver their contents directly to the cells. Liposomes are often used to deliver active ingredients such as vitamins, minerals, antioxidants, and other nutrients to the skin. They are also used to deliver drugs and other treatments to the skin. Liposomes are very safe and are not absorbed into the bloodstream, so they are an ideal delivery system for cosmetics⁵.

Liposomal drug delivery system:

Liposomes can also act as dermal carriers due to their being small, unilamellar, and designed with membrane flexibility. Therefore, liposomes are commonly used in dermal applications, either as protective systems for active ingredients or for their moisturizing properties. The use of the liposomal drug-delivery system for cosmetics was started in 1987, but nowadays they are frequently used in several hundred commercials in various forms like gels, creams, and moisturizers. The lipids used for liposomes contain moisture; therefore, as the liposomal vesicle ruptures, moisture adheres to the skin surface providing hydration. Because of these properties, liposomes are an excellent choice for cosmetic formulations designed especially for dry skin. Liposomes not only deliver moisture to skin cells but also create a barrier over the surface of the skin. Liposomal vesicles form an occlusive layer adhering to the skin surface. This occlusion promotes the penetration of encapsulated active ingredients into the skin and protects the cells from external stressors, such as sunlight and sweat. This facilitates delivery of the active ingredients to the outermost/deeper skin layers as desired for cosmetic products, for example, aqueous sun care products containing liposome-encapsulated ultraviolet filters are water-resistant. A moisturizer containing aloe vera leaf gel extract encapsulated liposomes which have antiwrinkle qualities was concluded as more effective than the application of the gel alone. Liposomes encapsulating CoQ10, a powerful antioxidant, are also beneficial to the skin. Larger vitamins, such as vitamin E, water-soluble vitamins, fat-soluble amino acids, and even chemically formulated active ingredients, can also be encapsulated into these liposomes successfully to formulate various skin care products ⁵.

Figure 1: Skin delivery of cosmetics.

Figure 2: Liposomes types.

The liposome-encapsulated cosmeceuticals are generally formulated as creams or gels. When applied onto the intact skin, the liposomal vesicle, due to its mimicking structure with the skin epidermis layer, is merged with the cell membranes and delivers the active pharmaceutical ingredients by trans-appendageal permeation through the skin ⁶. Further, the number of stability-related problems is reduced for various drugs effective in different skin diseases when they are in entrapped or encapsulated state in the liposomal vesicles. Additionally, the skin hypersensitivity reaction is also reduced when formulated these pharmaceuticals into liposomes ⁷. Thus, liposomes are gaining more interest in the development of cosmeceuticals for topical applications in the management of different skin disorders.

Table 2: Common Active Ingredients Encapsulated in Liposomes.

Active Ingredient	Function	Benefits of Liposomes Encapsulations
Retinol	Anti-aging	Improved penetration and protection from oxidation
Vitamin C	Brightening and anti-oxidant	Enhanced stability and bio availability
Co enzyme Q10 (CoQ10)	Anti-oxidant and anti-aging	Better penetration for Improved skin regeneration
Curcumin	Anti-inflammatory and anti-aging	Increased topical bioavailability

Recent uses of liposomes in the cosmeceutical field:

Liposomes in the antiaging formulation:

When we talk about skin ageing, we're talking about the countless stages of damage and deterioration that constantly alter the structural and functional changes in human skin with time or ageing⁸. Premature ageing can also occur as a result of prolonged exposure to several environmental variables, including ultraviolet (UV) light, particularly UVA or UVB, infrared radiation, sunlight, and air pollution. Natural skin ageing is a slow and irreversible process. UV exposure is the main environmental element that accelerates the ageing of the skin. The formation of reactive oxygen species (ROS) and nitric oxide as a result of prolonged and excessive sun exposure increases oxidative damage to DNA, including DNA strand breaks, purine or pyrimidine oxidation, lipid peroxidation, and damage to epidermal cells by cellular component destruction, which results in the appearance of lines and creases on the skin's surface and skin ageing. Furthermore, ROS production encourages skin cells to overexpress matrix metalloproteinases, which break down skin tissues. UV light exposure also damages the skin's connective structures, which causes the skin to lose its pliability and look⁹. To protect skin from the detrimental effects of UV radiation, a number of therapeutic compounds are utilised, such as retinoids (retinol and retinoic acid), vitamin C (ascorbic acid), hydroxy acids, vitamins B3, D3, E, and coenzyme Q10 (CoQ10). Even Nevertheless, using therapeutic compounds topically may raise significant safety concerns due to their stability, toxicity, and systemic exposure. According to Bi et al., Although vitamin D3 is an efficient medication for preventing skin from photo-aging, it has certain limitations, including sensitivity to air, high temperatures, and light as well as quick degradation in water and ethanol during the production of standard topical treatments. So they created a novel approach based on vitamin D3-encapsulated liposomes, and they showed that the aforementioned issues were diminished as well as the drug's stability ¹⁰. Due to their antioxidant properties and other vital functions, naturally occurring herbal components like Curcuma longa (Zingiberaceae) are said to be a viable option for anti-aging treatment by preventing the production of oxygen-free radicals and lipid peroxidation during UV exposure. In order to improve skin hydration and sebum content into the deeper skin layers, a study reported the use of Curcuma longa extract for use in UV-induced damaging of skin by incorporating it in different prototypes of vesicular systems like ethosomes, transferrosomes, and liposomes. This was done in order to counteract the negative effects of solar radiation and prevent photo-aging. The study came to the conclusion that liposomes, in particular, filled with curcuma longa extract, can be an excellent strategy to protect skin from UV radiation damage and preserve good skin health¹¹. Although the medicine of choice for treating skin ageing is curcumin (CU), creams and gels containing CU have little to no antiaging potential. According to reports, CU has poor topical bioavailability because of inefficient cutaneous absorption; as a result, only minute amounts of CU administered topically reach the dermis. Gupta and the team showed enhanced topical bioavailability of CU from the gel containing CU-loaded liposomes/ niosomes¹². With the aid of CU, they created a phosphatidylcholine complex and transformed it into phyto-vesicles. Additionally, they have created CU liposomes and niosomes. These three formulations were combined with carbopol for topical application in order to assess how well they compared to pure CU in terms of topical bioavailability. The antiaging potentials of several formulations were evaluated in mice under UV-induced oxidative stress. The study concluded that phytovesicles had more antiaging potential and that all three preparations were highly effective at boosting the antioxidant and antiaging activities of CU over pure CU. A natural flavonoid called glabridin has been suggested as a promising treatment option for people who have UVB-induced photoaging. Although glabridin is a fantastic skin-whitening chemical with significant antiaging potential, its poor epidermal penetration upon topical application restricts its effectiveness. Therefore, one team of scientists considered using liposomes to administer the medication. To increase bioavailability, they created glabridin-incorporated liposomes using the film dispersion method, and they gave them various characteristics¹³. Due to the downregulation of inflammatory cytokines expression, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-10, the fabricated liposomes were shown to be extremely effective in reducing UV-induced erythema formation onto the skin surface and also preventing leathery skin. Therefore, it can be inferred from this study that topical use of liposomal glabridin or comparable medications could be a very excellent technique for preventing UVB-induced ageing. Other natural antioxidants like vitamin E and its counterpart (trolox), are said to have a less potent antioxidant action than rosmarinic acid (RA). RA functions as a free radical scavenger and slows down the generation of lipid peroxidation in the deeper skin layers brought on by UV exposure. According to Yücel Aşk & colleagues, Ethosomes and Liposomes were created to supply RA. Their research showed that making anti-aging cosmeceuticals with RA-incorporated ethosomes and liposomes for transdermal application could be a great method to boost their potency¹⁴.

Liposomes in hair care:

Alopecia is a prevalent condition that affects both men and women and is characterised by a predominance in hair loss. The development of hair follicles and the life cycle of hair may be affected by genetic, inflammatory, environmental, hormonal, or a combination of these factors, resulting in hair loss. Androgenetic alopecia, one of the various kinds of alopecia, is quite prevalent and is brought on by decreased blood flow to the scalp's hair follicles. Additionally, it happens because of a larger concentration of dihydrotestosterone, which is hazardous to hair follicles. For the treatment of alopecia, conventional topical treatments are utilised to encourage hair growth. However, their usage is restricted due to their low compliance, intolerability, and limited performance as a result of various negative effects¹⁵. According to a study by Brotzu et al., liposomal formulation was used to treat alopecia. Their research established that several substances, including dihomo-linolenic acid (DGLA), S-equol, and propionyl-l-carnitine, had better anti-alopecia action when applied after loading into liposomes than the traditional topical preparation¹⁵. Early baldness, alopecia, and hair thinning were treated with the help of two commercial lotions called TRINOV Lozione Anticaduta Uomo and TRINOV Lozione Anticaduta Donna, both of which contained the aforementioned ingredients. S-equol inhibits 5-reductases, preventing the conversion of testosterone into the harmful anabolic hormone dihydrotestosterone, while DGLA, a precursor molecule of prostaglandin PGE1, works by improving microcirculation of the scalp. By improving lipid metabolism, propionyl-l-carnitine boosted the production of energy. In 30 men (TRINOV Lozione Anticaduta Uomo; mean age 46.66.4 years) and 30 women (TRINOV Lozione Anticaduta Donna; mean age 49.59.0 years) with androgenic alopecia, a group of researchers encapsulated these three agents into liposomes for transdermal application onto the scalp. They then compared the manufactured liposomes with conventional lotions. They concluded that liposomes containing DGLA, S-equol and propionyl-l-carnitine are more effective for treating androgen alopecia in both men and women. Due to the antioxidant potential along with the antiaging properties of CoQ10 on human hair, it can be used to treat individuals suffering from androgenic alopecia. But CoQ10 is a poor drug candidate when used in the actual development of a formulation for alopecia due to its poor aqueous solubility. The high molecular weight of CoQ10 limits its topical application leading to poor therapeutic outcomes. A recent work has been reported the improved therapeutic activity of CoQ10 by promoting skin penetration by developing various nano vesicular drug delivery systems, including liposomes for the management of androgenic alopecia. This study revealed better penetration of CoQ10 in liposomal form and concluded that nano vesicular carriers could open a new avenue in the treatment of scalp disorders^16,17.

Liposomes in wrinkles:

Inherent in the ageing process are wrinkles. On the skin's surface, wrinkles and creases are said to emerge as a result. Age causes the dermis layer to shrink and skin cells to divide more slowly. The principal structural proteins in the skin, collagen fibres and the elastin network, which can restore the skin's structure after stretching or contracting, support the skin's epidermis. The skin loses its capacity to hold onto moisture as it ages, and the oil-secreting glands work less effectively. Additionally, the skin becomes less elastic and shows a delayed healing capacity. A study was successfully conducted to show the safety and efficacy of photodynamic therapy along with a novel 0.5% liposome-encapsulated 5-aminolevulinic acid spray in the reduction of periorbital and nasolabial wrinkles in photo-aging. A baseline visit was conducted on 30 healthy adult participants (aged 35–65) with skin types I through III and type 2 photo-aging. After receiving three treatments with liposomes and a once-every-three-weeks strong pulsed light system, the depth of the wrinkles that had formed was measured using the modified Fitzpatrick wrinkle scale. The procedure had no side effects, and periorbital wrinkles seemed to become better overall more so than nasolabial wrinkles. By lessening the strength of facial muscle contraction and easing facial tension, the synthetic neuropeptide acetyl-hexapeptide-3 decreases lines and wrinkles. However, the large molecular size and hydrophilic property of this drug resulted in its poor permeation and diffusivity through the lipophilic stratum corneum. The multilamellar liposomes containing acetyl-hexapeptide-3 were developed by the thin film hydration technique. This liposome formulation showed improved skin permeation through the skin¹⁸. So, this study proved to be a great technique to formulate similar potent hydrophilic active pharmaceutical components and to manufacture anti-wrinkle cosmeceuticals for higher therapeutic effectiveness.

Liposomes in acne:

Propionibacterium acnes causes the chronic and common skin condition known as acne vulgaris, which affects the hair follicles, sebaceous glands, and arrector pili muscle of the human skin. Acne can manifest as inflammatory, noninflammatory, or a combination of the two types of lesions. Although it can be present in the back and chest as well, it primarily affects the face. Dead skin cells generally cause pores to clog or open onto the skin, which causes sebum (oil) to accumulate inside the pore. Different immune cells in the body contribute to the inflammation caused by acne by increasing the synthesis of pro-inflammatory cytokines like interleukin 1 (IL-1) and TNF-, which in turn causes hyperkeratinization of hair follicles and encourages inflammation¹⁹. Acne is typically treated with a variety of topical and systemic antibiotics, retinoids (such as isotretinoin, adapalene, and tazarotene), anti-inflammatory and/or antibacterial medications, and benzoyl peroxide (BPO). Galderma sells adapalene under the brand names Diferin and Epiduo (Lausanne, Switzerland). Diferin is available as a gel¹⁹ and a lotion. Epiduo, a topical gel that includes both adapalene and BPO, was approved by the US Food and Drug Administration in 2008. The unpleasant effects associated with these formulations, such as skin erythema, dryness, and itching, have been shown to dramatically lower patient compliance²⁰. As was already said, other medications can also treat acne, but they come with major side effects like teratogenicity, myalgias, and arthralgias (in the case of retinoids)¹⁹. A small number of commonly prescribed acne medications have reportedly been found to be inappropriate and ineffective at all stages of the acne life cycle. The pathogenic germs that cause acne are not affected by the retinoids' antibacterial properties. Contrarily, although antibiotics do have an antibacterial effect, it has been documented that they also impair the intestinal vital microflora and result in the development of antibiotic resistance in Propionibacterium acnes²¹. Sometimes hormonal treatment is used as an alternative to retinoids for corrective purposes, but once more, this suppresses the important hormones that the adrenal glands produce. As a result, as was already said, there is a pressing need to create safe and efficient medications for the treatment of acne that are based on cutting-edge drug delivery systems that can minimise adverse effects and increase patient compliance with the proper drug dosage. According to research published in the literature, liposomes in particular offer a novel way to address the problems with conventional anti-acne medications^19,22. A work by group of scientists reported the role of natural agents such as CU and lauric acid in acne. Azithromycin was contrasted with carbopol gels that contained cationic liposomes that were made from biocompatible lipids. Topical azithromycin reportedly provides a potent anti-acne effect. As a result, azithromycin liposomal gel served as a reference comparator when CU and lauric acid liposomes were manufactured. The produced liposomes were reported to connect with the negatively charged stratum corneum of the dermis easily and to be cytocompatible when used with various cell lines, including L929, HeLa, and MDA.-MB-231¹⁹. Based on results from in vitro skin permeation investigations, adapalene-encapsulated liposomes were created, characterised, and reported to have improved adapalene penetration capabilities from the liposomal formulation. Confocal microscopy findings showed that the liposomal formulation of adapalene reached the hair follicles in pig ear skin more efficiently than the two comparators (a medication solution and a straightforward gel formulation of adapalene). Adapalene liposomal encapsulation could also improve patient compliance while reducing negative effects. Thus, liposomes offer a suitable and promising carrier for adapalene's follicular targeting in the treatment of acne²³. Another study claimed that liposomes were used to administer both BPO and adapalene. The therapeutic efficacy and tolerability of BPO and adapalene-loaded modified liposomal gel for enhanced acne treatment were examined by the researchers. By using animal trials, the research showed that synthetic liposomes greatly increased dermal bioavailability with less possibility for skin irritation when compared to free medicines and papule density when compared to Epiduo²⁴. Cerasomes, which are formulations resembling liposomes encapsulated in cryptotanshinone, were created, and their in vivo performance following topical treatment in rat acne model was assessed. Following the ethanol injection procedure, the cerasomes were created and then characterised. Cerasome gel displayed a higher rate of penetration and significant buildup in the dermis layer of isolated rat skin, according to an in vitro permeation investigation Studies on in vivo pharmacokinetics demonstrated a maximum drug concentration, a rapid peak time, and a low clearance. The cerasome gel demonstrated enhanced anti-acne efficacy compared to a standard gel and contained cryptotanshinone, which effectively reduced the production of interleukin-1 and androgen receptors and has great potential for treating acne brought on by inflammation and excessive testosterone secretion²⁵.

Liposomes in psoriasis:

A chronic auto-immune disease caused by T lymphocytes, hyperproliferation of keratinocyte cells is a hallmark of psoriasis. The result is a reduced lifespan for the epidermis of the skin. Additionally, it modifies the desquamation process, leading to cytokine leakage from lesions on infected patients and the appearance of scaling markings on the skin. On the skin, the disease causes hyperproliferation and other inflammatory reactions. Interleukin (IL)-6, IL-23, IL-17, IL-22, and TNF- are just a few examples of the pro-inflammatory chemokines and cytokines that are overexpressed when it comes to this condition. According to the disease's severity, it can be divided into three types: mild, moderate, and severe. A mild condition causes the skin to become rashy, a moderate condition causes the skin to become scaly, and a severe disease causes the skin to become itchy²⁶. Topical therapy is still the main treatment for psoriasis. Drug molecules that have an affinity for the tissues of the skin and actions that target other inflammations should be chosen to treat psoriasis. When taken in higher doses, the majority of currently available medicines result in systemic toxicity and drynessNumerous systematic approaches for topical dispersion have been studied by researchers, including spray, nanogels, hydrogels, micro/nanoemulsion, liposomes, nanocapsules, and transdermal delivery ²⁶. N-(1-(2,3-dioleoyloxy) propyl)-N, N, N-trimethylammonium chloride and cholesterol were used to make cyclosporine cationic liposomes, which were successful in treating psoriasis. They created cyclosporine liposome gel and employed it in a psoriatic plaque model caused by imiquimod. The liposomal gel decreased psoriasis symptoms and the key psoriatic cytokines TNF-, IL-17, and IL-22, which are responsible for the onset of psoriasis ²⁷. It was stated in another work that methotrexate (MTX) is used to treat psoriasis. MTX was administered topically by entrapping it in deformable liposomes consisting of phosphatidylcholine and oleic acid. The quantities used were 0.05%, 0.1%, 0.25%, and 0.50%. The study reported encouraging findings regarding the performance of the created liposomes in imiquimod-induced psoriasis in a mouse model. Furthermore, the study demonstrated that liposomal MTX (0.05 and 0.1%) significantly decreased psoriatic tissue thickness score compared to traditional MTX injection in psoriatic mice in a dose-dependent manner. Further, a study was performed to identify the different inflammatory factors responsible for psoriasis development. Various pathological investigations of the skin tissues of mice during treatment with liposomes demonstrated better performance without any associated organ toxicity and without any effect on the blood cell counts from liposomal MTX²⁸. Thus, the study came to the conclusion that the use of MTX-loaded deformable liposomes may be a promising approach for the creation of future nanomedicines for the treatment of human psoriasis. Phase IV clinical trial (NCT03348462) is being conducted on the liposomal formulation of anthralin for short-contact topical application in the treatment of psoriasis vulgaris.

Liposomes in pigmentation disorder:

Skin pigmentation disorders are characterised by variations in skin tone. Melanin, a pigment, determines the colour of the skin. Pigmentation disorders are brought on by variations in the melanin release from the melanocytes in the deeper layers of skin tissue. Changes in skin colour are influenced by oxidised and reduced haemoglobin levels, carotenoid concentration, vascular health, skin thickness, light refraction and absorption properties, and skin absorption. Melanin secretion activity had the greatest influence on changes in skin tone out of all the factors. The term "pigmentation" describes colour changes in the skin, hair, and eyes that are a result of genetic variation, melanocyte abundance, and the distribution of melanin-producing cells. The skin darkens when the body produces too much melanin, and lightens when it produces too little. Therefore, the pigmentation issue could be either hyper- or hypopigmented. Tyrosinase is a critical enzyme in the formation of melanin and is also implicated in the development of other pigmentation disorders, including vitiligo, albinism, and hyperpigmentation conditions like melasma and lentigo, among others²⁹.

In hypopigmentation, liposomes A skin condition associated with hypopigmentation is vitiligo. Due to the loss of melanocytes, the cells that produce melanin, it is characterised by white spots on the skin's surface. It is also understood that oxidative stress contributes to and triggers vitiligo. The most often utilised therapeutic techniques include topical corticosteroid administration, UV phototherapy, and calcineurin inhibitors. Two examples of potential uses for UV therapies include phototherapy (UVB) and photochemotherapy (also known as PUVA therapy employing psoralen with UVA). The two medications of preference for vitiligo treatment are resveratrol (RSV) and psoralen. There are many topical treatments available for the management of vitiligo, including calcineurin inhibitors (ointment and cream), trioxsalen (solution), methoxsalen (solution and cream), corticosteroids (solution, gel, cream, and ointment), and methoxsalen (solution and cream). Patient compliance is however limited by side effects and ineffectiveness. As a result, numerous novel drug delivery techniques have been described in the literature for enhancing the topical administration of many medications that are useful in treating hypopigmentation. The innovative carriers work by either enhancing medication penetration, which encourages drug localization into the skin's underlying epidermal layer, or by minimising side effects, which increases patient compliance^30,31. RSV, an antioxidant, can decrease vitiligo brought on by oxidative stress. RSV, however, has a poor water solubility that restricts its topical administration, and psoralen also has a limited skin penetration rate that prevents it from reaching the melanocytes in the deeper layers of the skin at a concentration necessary for effectiveness. Doppalapudi et al. shown in a study that the combination of psoralen and RSV can treat vitiligo by administering the medication in a liposomal form. They claim that combining UVA and Psoralen helps melanocytes produce more melanin and have higher tyrosinase activity. For the purpose of assessing the efficacy of PUVA and antioxidant combination therapy for vitiligo, they reported the preparation of ultradeformable liposomes using 3ß-[N-(N, N-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-Chol), cholesterol, and sodium deoxycholate co-loaded with psoralen and resveratrol. The efficiency of the liposomal formulation was evaluated using the B16F10 cell line. The potential resveratrol activity of in vitro antioxidant research was employed to ascertain the free radical scavenging capacity of these carriers [Doppalapudi S, 2017]. Due to their antioxidant, anti-inflammatory, and proliferative properties, many natural polyphenolic chemicals, including baicalin and berberine, are utilised in the treatment of de-pigmentation disorders of the skin, such as vitiligo. However, its adequate efficacy to accomplish in the treatment of vitiligo is limited by poor water solubility and poor absorption after topical application by standard creams or gels³³. According to a study, it is possible to create extremely deformable liposomes using baicalin and berberine, which offers a promising solution to the medications' solubility issue by improving their capacity to quickly and effectively penetrate the epidermis. The created liposomes were negatively charged and tiny (100nm). They also discovered that these polyphenol-containing vesicles penetrated the epidermis of newborn pigs more deeply than intact polyphenols in PBS or a 5% sorbitol in water solution. Baicalin and berberine vesicles' ability to promote melanogenesis and skin pigmentation was also investigated in melanocytes, and the results showed notable antioxidant and photoprotective benefits. Additionally, these formulations proved efficient in preventing cell damage caused by oxidative stress. The liposome could, therefore, increase tyrosinase activity and accelerate melanin synthesis. As a result, they came to the conclusion that extremely deformable vesicles of baicalin or berberine, mostly in their grouping, could be a promising strategy for managing vitiligo³³.

Liposomes in hyperpigmentation and melisma:

Pregnancy patches, chloasma, and melasma all mean the same thing. The skin's hepermelanogenesis causes melasma, a chronic acquired pigmentation condition. Sun-exposed areas get melanin malfunction as a result of excessive melanin production. Chloasma, also referred to as the pregnancy mask, is more common in women than in men. Although the precise cause is still a mystery, certain recognised triggering events, such as the use of oral contraceptives, pregnancy, and menopause, have been found. Clinically, irregular dark macules with defined borders are distributed symmetrically. After sun exposure, they are usually found on the face. Asian women typically experience melasma in their thirties or forties. Long-term exposure to UV radiation, the activation of the female sex hormone, and genetic predisposition have all been associated with melisma^34,35. The initial focus of treatment must be on the underlying cause. Additionally, oligopeptides, hydroquinone, 4-n-butylresorcinol, an extract of the herb Silybum marianum, silymarin, and orchid can be utilised locally. Chemical peeling agents like tretinoin, trichloracetic acid, glycolic acid, kojic acid, etc. are also effective. ^36,
37. Hydroquinone (1, dihydroxybenzene), a tyrosinase inhibitor, can be successfully administered in the form of liposomes to boost its therapeutic efficacy in the management of melasma, according to a pilot study by Taghavi and colleagues. By using the fusion process, 4% hydroquinone was encapsulated in liposomes and its physiochemical makeup was determined. They contrasted the produced hydroquinone liposomes' therapeutic effectiveness with that of regular hydroquinone. Twenty female melasma patients were included in a double-blinded, randomised clinical trial. For three months, they were advised to topically apply liposomal hydroquinone and regular hydroquinone to the two opposing sides of their faces. The Melasma Area and Severity Index (MASI) was used to compare the therapeutic efficacy of the two treatments. The MASI results from this plot study showed that liposomal hydroquinone had a sizable therapeutic effect on melisma ³⁸. Using soybean lecithin, Ghafarzadeh and Eatemadi created liposome-encapsulated aloe vera gel extract. Small unilamellar vesicles with a diameter of less than 200 nm were the liposomes that were produced. Melasma patients received a gel application of the liposomal gel. Two groups of pregnant women with melasma were administered liposomes in the double-blinded, randomised clinical trial and contrasted with the control group of patients. Due to their ease of percolation and lack of side effects, liposome-encapsulated aloe vera gel extract was superior to aloe vera gel in reducing the severity of melasma and lightening melasma in pregnancy ³⁹. According to another study, a cream that contains liposomes encapsulated with RSV and 4-n-butylresorcinol is more successful at treating melasma. The melanin index (MI) of the preauricular area and the melasma lesion (lesional MI and non-lesional MI, respectively) of the skin were measured at weeks 0 (baseline), 2, and 4.

Liposomes in fungal infection of the skin:

The threat posed by fungi can harm the skin, nails, hair, and mucous membranes on a superficial level or can penetrate the systemic circulation, distressing the entire body. The capacity of medications to penetrate the skin, particularly the dead stratum corneum, and reach the lower layers of the skin (viable epidermis), is a key factor in the success of topical antifungal therapy⁴⁰. Onychomycosis, a fungus infection that affects the nails, is sometimes brought on by dermatophytes⁴¹. The antifungal drug croconazole, a synthetic imidazole, is helpful in treating yeast and dermatophyte- and Candida albicans-induced fungal infections. For topical distribution, two alternative croconazole formulations—liposomal-based and microemulsion-based gel formulations—were created and compared to standard gels made with various polymers (chitosan, Carbopol 971P, Poloxamer 407, and sodium carboxymethyl cellulose). Based on the drug release/skin permeability profile in the traditional gel, Carbopol 971P was chosen for the incorporation of liposomal and microemulsion of croconazole. In comparison to various fungi, both experimental formulations were more effective. However, this study finds that products based on microemulsions are superior to gels based on liposomes ⁴². In a different study, miconazole nitrate was loaded into ultraflexible liposomes and contrasted with miconazole-containing conventional liposomes. In in vitro skin penetration assays, the ultrafexible liposomes demonstrated better encapsulation efficiency and were more successful in delivering the medication to the skin ⁴³. A polyene antifungal medication called amphotericin B was placed inside elastic liposomes to treat dermatoses brought on by Leishmania species and other fungal infections. In this work, the deformation capacity was assessed using two different types of edge activators in the liposome formulation, such as sodium cholate and Tween 80. The liposomes made with Tween 80 displayed a better ability for deformation. This outcome can be attributable to the surfactants' molecular makeup and subsequent integration into the lipid bilayer structure. Amphotericin B was able to deeply penetrate human skin when deformable liposomes were applied in a non-occlusive manner, reaching the living epidermis ⁴⁴. For the treatment of onychomycosis, the effectiveness of the terbinafne hydrochloride-loaded liposome film formulation was compared to that of ethosome, liposome poloxamer gel, terbinafne-loaded liposome, and ethosome chitosan gel formulations. For all liposome-based film formulations, the medication was collected in the nail plate within the therapeutic range. Improved antifungal efficacy on fungal nails was demonstrated by a liposome formulation containing film. In order to effectively treat onychomycosis, Shah and colleagues were able to increase the ungual permeability of terbinafine HCl when it was administered in the form of a liposome-loaded nail lacquer. They utilized a three-factor, three-level Box-Behnken design to optimize the formulation utilizing the QbD Approach. It was discovered that nail lacquer with a permeation enhancer has inferior translingual permeability for terbinafne HCl compared to nail lacquer loaded with liposomes. Therefore, onychomycosis might be effectively treated using the liposomal formulation ⁴⁵.

Cosmeceuticals are cosmetic products with biologically active components that have drug-like benefits. Cosmeceuticals are currently rapidly growing segments encompassing the personal care industry and numerous topical cosmetics-based therapies for treating different skin conditions. The barrier nature of the skin causes limitations to topical treatment. The effectiveness of this cosmeceutical product has been enhanced a few folds by using nanotechnological modifications ⁴⁶.

The cosmeceutical industry is expanding exponentially as a result of the rising daily demand for cosmeceutical products. Nanotechnology is an example of contemporary technology for the twenty-first century and presents tremendous opportunities for both research platforms and the market. Significant technical and financial aspirations have been raised by the rapid adoption and commercialization of nanotechnology in cosmeceuticals. Due to their unique properties and capacity for improved permeability and bioavailability, liposomes in particular attracted a great deal of attention in the formulation of topical preparations. Therefore, liposome-based cosmeceutical products could be a godsend for treating skin conditions.

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Received on 29.10.2024 Revised on 21.02.2025

Accepted on 28.04.2025 Published on 02.08.2025

Available online from August 08, 2025

Research J. Pharmacy and Technology. 2025;18(8):4014-4023.

DOI: 10.52711/0974-360X.2025.00577

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