INTRODUCTION:

Targeted drug delivery implies picky and effective localization of pharmacologically active component at preselected target in remedial attention, while confining its access to nontarget areas, therefore maximizing the effectiveness of the medicine.¹ Skin is the largest, fluently accessible organ for original and systemic medicine administration. But the skin behaves as a unresistant hedge to the penetrant patch. Cosmeceuticals refers to the combination of cosmetics and medicinals. Cosmeceuticals are ornamental products with biologically active constituents purporting to have medical or medicine such like benefits.²

The main barrier is located in the outermost layer of the skin, the stratum corneum, which contains flattened dead epidermal cells (corneocytes) embedded in hydrophobic lipid domains³the corneocytes of stratum corneum are entirely girdled by crystalline lamellar lipid regions. The cell boundary, the cornified envelope, is a veritably densely cross-linked protein structure, which reduces immersion of medicines into the cells.⁴ The carrier is one of the most important realities needed for successful targeted medicine delivery. Accordingly, as a vehicle for active substances and targeting to skin layers, lipidic carriers similar as liposomal systems are gaining further interest. Lipid- grounded medicine delivery is becoming further popular because lipid accoutrements are fluently characterized, contain a high range of well defined/ permitted surfactant motes and can be developed for several administration routes. These systems are particularly suitable for topical delivery because numerous suitable composites are answerable in these accoutrements, they don't irritate the skin and they've extremely low acute and chronic toxicities.⁵

Liposomes:

Derived from the Greek words 'lipo' and 'soma,' the term 'liposome' describes their fatty constitution and structural composition, respectively. These spherical vesicles possess a membrane consisting of a bilayer composed of phospholipids and cholesterol.⁶Liposomes, being one of the most extensively studied drug carrier systems, offer a unique advantage due to their structural arrangement. This arrangement allows for the incorporation of lipophilic drugs within the lipid bilayers and hydrophilic drugs within the aqueous compartment. The composition, size, surface charge, and drug solubility play crucial roles in determining the drug release from liposomes, as well as their stability and pharmacokinetic profiles.⁷In order to specifically target the active ingredients, the lipid bilayer of liposomes has the capability to merge with the cell membrane, facilitating the delivery of the liposome contents directly into the targeted cells.⁷

The classification of liposomes is based on their size and lamellarity, which refers to the number of bilayers. There are three main categories: small unilamellar vesicles (SUVs) or oligolamellar (OLVs), large unilamellar vesicles (LUVs), and multilamellar vesicles (MLVs).⁸

Figure no. 1. Structure of Liposome.

Known are different penetration pathways into and through the stratum corneum: primarily the transepidermal pathway, characterized by intercellular penetration, and the transappendageal routes, which involve the sweat glands and hair follicles.⁹The use of liposome formulations in skin gels or creams has sparked considerable interest in the field of dermatology and cosmetics due to the significant enhancement in therapeutic activity demonstrated by liposomal formulations compared to nonliposomal counterparts.¹⁰

Advantages of topical liposomes:

The reasons for utilizing liposomes in drug delivery include the following:

1. Avoidance of serious side effects and incompatibilities that may result from the drug's ability to localize, thereby preventing systemic absorption;

2. Enhanced drug accumulation at the skin through the mimic epidermis composition, facilitating liposome substantivity with biological membranes;

3. The non-toxic and biodegradable nature of liposomes and

4. The ease of scaling up production for manufacturing purposes.

5. Encapsulating both water- and lipid-soluble active components can be achieved.^11,12

Indications for liposomes as drug carriers in cosmeceutics:

1) Acne:

Acne vulgaris, commonly known as acne, is a prevalent skin disease that affects over 85% of teenagers, with adolescence being the most common age group it afflicts.¹³ Acne is characterized by inflammation of sebaceous glands and is linked to the immune response triggered by several Gram-positive bacteria, primarily Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis, which colonize follicles rich in sebum.¹⁴

The application of liposomal drug lotions, specifically those prepared using either soya lecithin and cholesterol or hostaphate and cholesterol, has shown significantly better efficacy in the clinical treatment of acne vulgaris compared to non-liposomal lotions. Notably, when treating pustules, there was a remarkable 77% improvement in the clinical condition compared to the initial number. In a comparative study, the use of conventional lotion solutions resulted in a 42.9% decrease in the total number of lesions after a 4-week treatment.

Non-liposomal emulsion lotions showed a slightly better reduction of 48.3% in lesions, while liposomal emulsion lotions demonstrated the most substantial improvement, with a remarkable 62.8% reduction in the total number of lesions after the 4-week treatment period. These findings provide strong support for the potential development of topical therapy products utilizing the liposomal dosage form. The use of liposomes appears to be superior to existing dosage forms, indicating a promising avenue for the enhancement of acne treatment effectiveness.¹⁵

2) Hyperpigmentation and melasma:

Custom and considerable cosmetic problems, facial and neck pigmentations commonly afflict middle-aged women due to both endogenous factors (hormones) and exogenous factors (cosmetics, perfumes, sun exposure). These pigmentations often become significant causes of emotional distress and are of paramount concern for affected individuals.¹⁶

In a study involving 23 patients diagnosed with melasma, the effects of liposomal 4-n-butylresorcinol 0.1% cream and the vehicle alone were compared. The patients applied either the liposomal cream or the vehicle to each side of their face twice daily for a duration of 8 weeks. The results showed that the liposomal 4-n-butylresorcinol 0.1% cream was well-tolerated and exhibited significantly higher efficacy in treating melasma compared to the vehicle alone. In over 60% of the patients, the liposomal cream demonstrated notable effectiveness in addressing the condition.¹⁷

3) Vitiligo:

Characterized by well-circumscribed milky white macules, vitiligo is an acquired idiopathic dermatological disorder where the skin's melanocytes suffer from damage.¹⁸Enhancing penetration into the hair follicles is achieved by encapsulating it into liposomes. Subsequently, the activation of khellin with UV light stimulates the melanocytes in the hair follicles, leading to a cosmetic result that satisfied seventy-five percent of the patients.¹⁹

4) Alopecia:

The most common cause of hair loss in men is androgenic alopecia, also known as male pattern hair loss, which is characterized by progressive hair thinning in genetically susceptible individuals. Hair follicles play a crucial role in the penetration and reservoir behavior of topically applied liposomes, underscoring their significance in this context.²⁰Minoxidil is widely utilized for treating androgenic alopecia, its mechanism of action on hair follicles remains unknown.²¹

The study conducted involved preparing liposomes and niosomes loaded with minoxidil, and then assessing their percutaneous (through the skin) absorption using vertical diffusion franz cells and human skin in vitro. The findings of this research indicate that liposomes, in particular, have significant potential for targeted drug delivery to the skin. As a result, they could be considered a viable and practical therapeutic option for treating skin conditions, including hair loss.²²

5) Antioxidants:

A complex process, skin aging encompasses various genetic, environmental, and hormonal mechanisms. Intrinsic and extrinsic aging are influenced significantly by free radicals. Intrinsic aging involves the production of free radicals by cell metabolism as part of the chronologic aging process. Conversely, in the extrinsic aging process, exogenous factors like UV exposure, cigarette smoking, and alcohol consumption contribute to the emergence of free radicals.One of the most effective free radical scavengers with the potential to decelerate the damaging effects of skin aging is sodium ascorbyl phosphate (SAP).²³Fabricating SAP-loaded liposomes for skin photoprotection, it was concluded that liposomes enhance SAP penetration through the stratum corneum when compared to the aqueous formulation of SAP used as a control.²⁴

Figure No. 2. Liposomes for delivery of antioxidants in cosmeceuticals.

6) UV protection:

The skin experiences a diverse range of acute and chronic effects due to UV radiation. Acute responses, such as erythema, manifest when exposed to UV radiation. In the long term, UV exposure leads to photoaging and photocarcinogenesis, which are believed to result from immune suppression and the induction of mutations.²⁵

UV-blocking effects exhibited by lipidic delivery systems, like liposomes, depend on lipid composition and particle size. Smaller particle sizes are associated with higher sunscreen activity. In vitro examinations of tested pigments (BaSO4, SrCO3, and TiO2) incorporated into the lipid matrix of carnauba wax/decyloleate revealed elevated Skin Protection Factor (SPF) values.²By utilizing the stripping method on the mid-volar forearms of six volunteers with a dose of 2 mg/cm2, the impact of different vehicles (conventional o/w emulsion and multilamellar and small unilamellar liposomes) on the penetration of octyl methoxycinnamate, a UV absorber, into the stratum corneum was investigated. The study's findings suggest that multilamellar liposomes could serve as a superior vehicle for octyl methoxycinnamate as a sunscreen. This is attributed to their slightly better SPF compared to the conventional formulation, as well as their ability to retain more of the sunscreen in the stratum corneum, thereby reducing its penetration into the deeper layers of the skin.²⁶

CONCLUSION:

In conclusion, the development of liposomal carriers has opened new horizons in the field of cosmeceuticals and dermatology. Liposomes offer promising advantages as drug delivery vehicles, delivering therapeutics into skin layers and enhancing skin hydration. They have shown potential in treating various dermatological disorders and improving the effectiveness of cosmeceutical products. However, further research and refinement are necessary to overcome challenges related to commercialization, such as cost and physical stability. Clinical data and in vivo studies have demonstrated the efficacy of liposomal formulations in topical drug delivery, encouraging future exploration of other indications for liposomal cosmeceuticals in dermatology. With continued research and development, liposomes are poised to play a key role in the future of cosmeceutics and offer innovative solutions for skin treatments.

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Received on 31.12.2023 Modified on 12.03.2024

Research J. Topical and Cosmetic Sci. 2024; 15(1):43-46.

DOI: 10.52711/2321-5844.2024.00008