Nanocosmeceutical and Emerging Trends in Pharmacy

Abstract

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nano cosmetics and nano cosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. Novel nanocarriers like liposomes, niosomes, nanoemulsions, microemulsion, solid lipid nanoparticles, nanostructured lipid carrier, and nanospheres have replaced the usage of conventional delivery system. These systems enhance the bioavailability, stability, and efficacy of active ingredients, offering controlled release and targeted delivery features that are crucial for optimizing cosmetic results. Nanotechnology facilitates improved penetration of actives into the skin, protects ingredients from degradation, and ensures sustained release, thereby enhancing the therapeutic effectiveness of cosmeceuticals. This review highlights the various novel carriers used for the delivery of cosmeceuticals, their positive and negative aspects, marketed formulations, and their toxicity.

Keywords

Introduction

       
           
       
Figure 1:  Liposomes

Liposomes are most widely used for the cosmeceutical preparations. They are the vesicular structures having an aqueous core which are enclosed by a hydrophobic lipid bilayer [6]. The main component of liposome lipid bilayer is phospholipids; these are GRAS (generally recognized as safe) ingredients, therefore minimizing the risk for adverse effects [7]. To protect the drug from metabolic degradation, liposome encapsulates the drug and releases active ingredients in a controlled manner [8]. Liposomes are suitable for delivery of both hydrophobic as well as hydrophilic compounds. Their size varies from 20 nm to several micrometers and can have either multilamellar or unilamellar structure [9].  Antioxidants such as carotenoids, CoQ10, and lycopene and active components like vitamins A, E, and K have been incorporated into liposomes, which are used to amplify their physical and chemical stability when dispersed in water[10].  Phosphatidylcholine is the key component of liposomes which has been used in various skin care formulations like moisturizer creams and so on and hair care products like shampoo and conditioner due to its softening and conditioning properties. Due to their biodegradable, nontoxic, and biocompatible nature, liposomes are used in variety of cosmeceuticals as they encapsulate active moiety[11]. Vegetable phospholipids are widely used for topical applications in cosmetics and dermatology because of their high content of esterified essential fatty acids. For topical applications in cosmetics and dermatology vegetable phospholipids are being widely used as they have high content of esterified essential fatty acids. After the application of linoleic acid, within a short period of time the barrier function of the skin is increased and water loss is decreased. The transport of linoleic acid into the skin is done by these phospholipids [12,13]. In a clinical study, it was proven that flexible liposomes help in wrinkle reduction and show effects like decreasing of efflorescence in the acne treatment and an increase in skin smoothness [14]. Liposomes are being developed for the delivery of fragrances, botanicals, and vitamins from anhydrous formulations, such as antiperspirants, body sprays, deodorants, and lipsticks. They are also being used in antiaging creams, deep moisturizing cream, sunscreen, beauty creams, and treatment of hair loss[15]. Several positive and negative aspects of liposomes are discussed[16].

Table 1: Various Marketed Formulations of Liposomes

2.2 Niosomes

Niosomes are defined as vesicles having a bilayer structure that are made up by self-assembly of hydrated nonionic surfactants, with or without incorporation of cholesterol or their lipids[20].   Niosomes can be multilamellar or unilamellar vesicles in which an aqueous solution of solute and lipophilic components are entirely enclosed by a membrane which are formed when the surfactant macromolecules are organized as bilayer[21]. Size ranges from 100 nm to 2 m in diameter. Size of small unilamellar vesicles, multilamellar vesicles, and large unilamellar vesicles ranges from 0.025–0.05 μm, =>0.05 μm, and 0.10 μm, respectively[22]. Major niosomes components include cholesterol and nonionic surfactants like spans, tweens, brijs, alkyl amides, sorbitan ester, crown ester, polyoxyethylene alkyl ether, and steroid-linked surfactants which are used for its preparation[23] Niosomes are suitable for delivery of both hydrophobic as well as hydrophilic compounds. As a novel drug delivery system, niosomes can be used as vehicle for poorly absorbable drugs[24]. It provides encapsulation to the drug, due to which the drug in the systemic circulation is for prolonged period and penetration is enhanced into target tissue. Niosomes overcome the problems associated with liposomes, like stability problems, high price, and susceptibility to oxidation[25]. Niosomes are used in cosmetics and skin care applications since skin penetration of ingredients is enhanced because it possesses the property of reversibly reducing the barrier resistance of the horny layer, allowing the ingredient to reach the living tissues at greater rate. There is increased stability of entrapped ingredients and improvement in the bioavailability of poorly adsorbed ingredients. There are many factors affecting formation of niosomes, namely, nature and structure of surfactants, nature of encapsulated drug, membrane composition, and temperature of hydration which influences shape and size[26]. Specialized niosomes are called proniosomes; these are nonionic based surfactant vesicles, which are hydrated immediately before use to yield aqueous niosome dispersions. To enhance drug delivery in addition to conventional niosomes, proniosomes are also being used [27,28].

Table 2: Various Marketed Formulation and Uses of Niosomes

 2.3 Solid Lipid Nanoparticles

       
           
       
 Figure 3:  Solid Lipid Nanoparticles

Solid lipid nanoparticles are among the nanotechnologies extensively used in both pharmaceuticals and cosmeceuticals. Commercially, many cosmeceutical companies produce cosmeceuticals using this technology to enhance beauty and therapy. 50 to 1000 nm is the size range of solid lipid nanoparticles [32] .  They are composed of single layer of shells and the core is oily or lipoidal in nature. Solid lipids or mixtures of lipids are present in the matrix drug which is dispersed or dissolved in the solid core matrix. Phospholipids hydrophobic chains are embedded in the fat matrix. These are prepared from complex glycerides mixtures, purified triglycerides, and waxes; liquid lipid is replaced by solid lipid or blend of solid lipid which is solid at body and room temperature and is stabilized by surfactants or polymers[33]. Lipophilic, hydrophilic, and poorly water-soluble active ingredients can be incorporated into SLNs which consist of physiological and biocompatible lipids. With the use of biocompatible compounds for preparing SLN, toxicity problems are avoided[34]. Two principle methods for preparation of SLNs are high pressure homogenization method and precipitation method. Controlled release and sustained release of the active ingredients are possible; SLN which has drug enriched core leads to a sustained release and SLN having drug enriched shell shows burst release.  Solid lipid nanoparticles have advantages in stability, higher production, and long-term storage compared to other conventional and nano delivery techniques.

Table 3: Various Marketed Formulation and Uses of SLN

2.4 Nanostructured Lipid Carriers (NLC)

Nanostructured lipid carriers are considered as the second generation of the lipid nanoparticles. NLC have been developed so that the drawbacks associated with SLN can be overcome. NLC are prepared through blending by solid lipids along with spatially incompatible liquid lipid leading to amorphous solids in preferable ratio of 70 : 30 up to 99.9 : 0.1 being solid at body temperature [37,38]. NLC are mainly of three types on the basis of which the structure is developed according to the formulation composition and production parameters, namely, imperfect type, amorphous type and multiple type. The particle size ranges from 10 to 1000 nm[39] .  In October 2005, the first products containing lipid nanoparticles were introduced in the cosmetic market, namely, NanoRepair Q10® cream and NanoRepair Q10® serum, Dr. Rimpler GmbH, Germany, offering increased skin penetration. Currently there are more than 30 cosmetic products available in the market containing NLC[40,41] .

Table 4: Various Marketed Products and Uses of NLC

2.5 Nanoemulsions

Nanoemulsions are considered as the kinetically or thermodynamically stable dispersion of liquid in which an oil phase and water phase are in combination with a surfactant. Their structure can be manipulated on the basis of method of preparation, so as to give different types of products. Depending on the composition different types of nanoemulsions are oil in water, water in oil, and bicontinuousnanoemulsion. They exhibit various sizes ranging from 50 nm to 200 nm. These are dispersed phase which comprises small particles or droplets, having very low oil/water interfacial tension[46]. They have lipophilic core, which is surrounded by a monomolecular layer of phospholipids, making it more suitable for delivery of lipophilic compounds.  Nanoemulsions are widely used as medium for the controlled delivery of various cosmeceuticals like deodorants, sunscreens, shampoos, lotions, nail enamels, conditioners, and hair serums[47] .  In cosmetics formulation, nanoemulsions provide rapid penetration and active transport of active ingredients and hydration to the skin.

Table 5: Various Marketed Products Name and Uses of Nanoemulsion

2.6 Gold Nanoparticles

       
           
       
Figure 6 : Structure of Gold Nanoparticles

Nanogold or gold nanoparticles exhibit various sizes ranging from 5 nm to 400 nm. in determination of their properties[51]. They exhibit different shapes such as nanosphere, nanoshell, nanocluster, nanorod, nanostar, nanocube, branched, and nanotriangles. Shape, size, dielectric properties, and environmental conditions of gold nanoparticles strongly affect the resonance frequency. The color of nanogold ranges from red to purple, to blue and almost black due to aggregation[52]. Gold nanoparticles are inert in nature, highly stable, biocompatible, and noncytotoxic in nature. Nanogold is very stable in liquid or dried form and is nonbleaching after staining on membranes; they are also available in conjugated and unconjugated form[53]. They have high drug-loading capacity and can easily travel into the target cell due to their small size and large surface area, shape, and crystallinity[54]. Main properties of nanogold in beauty care consist of assets, namely, acceleration of blood circulation, anti-infammatory property, antiseptic properties, improvising frmness and elasticity of skin, delaying aging process, and vitalizing skin metabolism [55].

Table 6: Various Marketed Products Name and Uses of Nanoemulsion

       
           
       
2.7 Dendrimers

       
           
       
Figure7: Structure of Dendrimers

The term “dendrimer” arises from two Greek words: namely, “Dendron” that means tree and “Meros” meaning part. Dendrimers are highly branched, unimolecular, globular, micellar nanostructure, and multivalent nanoparticles whose synthesis theoretically affords monodisperse compounds. A dendrimer is typically built from a core on which one or a number of successive series of branches are engrafted in an arborescent way and often adopts a spherical three-dimensional morphology[61]. Generation of the dendrimer is determined by total number of series of branches: if it has one series of branches, then it is first-generation dendrimer; if it has two series, then it is second generation and so on. They are extremely small in size, having diameters in the range of 2–20 nm [62]. Its other properties like monodispersity, polyvalence, and stability make it an ideal carrier for drug delivery with precision and selectivity. To attach biologically active substances for targeting purpose terminal groups are modified. Dendrimers provide controlled release from the inner core and drugs are incorporated in interior as well as being attached on the surface[63] .  Dendrimers are new class of macromolecular architecture and are also being used as nanotechnology based cosmeceuticals for various applications like in hair care, skin care, and nail care. Dendrimers have utility in various cosmetic products like shampoos, sunscreen, hair-styling gels, and antiacne products[64]. Companies like L’Oreal, The Dow Company, Wella, and Unilever have several patents for application of dendrimers in cosmeceuticals. 

       
           
       
Figure 8:  Structure of Cubosomes

Cubosomes are the advanced nanostructured particles which are discrete, submicron, and self-assembled liquid crystalline particles of surfactants with proper ratio of water that provides unique properties. Cubosomes are formed by self-assembled structures of aqueous lipid and surfactant systems when mixed with water and microstructure at a certain ratio[65]. Cubosomes are bicontinuous cubic liquid phase, which encloses two separate regions of water being divided by surfactant controlled bilayers and wrapped into a three dimension, periodic, and minimal surface, forming a strongly packed structure[66]. They consist of honeycombed (cavernous) structure and they appear like dots which are slightly spherical in structure. They exhibit size range from 10 to 500 nm in diameter. They have ability to encapsulate hydrophilic, hydrophobic, and amphiphilic substances. Cubosomes have relatively simple preparation methods; they render bioactive agents with controlled and targeted release, possess lipid biodegradability, and have high internal surface area with different drug-loading modalities[67,68]. Cubosomes are an attractive choice for cosmeceuticals, so for this reason a number of cosmetic giants are investigating cubosomes. Various patents have been filed regarding the cosmetic applications of cubosomes.

       
           
       
Figure no.9

4.0classes Of Nanocosmeceuticals

       
           
       
Figure 10:  Classes of Nanocosmeceuticals [30].

4.1 Hair Care

       
           
       
Figure 26: Routes Of Exposure of Nanoparticles

Health hazard caused by nanoparticles to the humans depends on the degree of exposure and the route through which they access the body. Inhalation, ingestion, and dermal routes are the possible routes by which humans can get exposure to the nanoparticles. Routes of exposures of nanoparticles[75]. are given in figure 26.

6.0 Ways to Minimize Toxicity of Nanocosmceuticals

Minimizing the toxicity of nanocosmeceuticals is crucial to ensure their safe use. Here are some ways to minimize toxicity:

6.1 Physical Modifications

1. Size control: Controlling the size of nanoparticles can reduce toxicity. Smaller particles may be more toxic due to their larger surface area.

2. Shape modification: Modifying the shape of nanoparticles can also reduce toxicity. For example, spherical particles may be less toxic than rod-shaped particles.

3. Surface coating: Coating nanoparticles with biocompatible materials, such as lipids or polymers, can reduce toxicity.

6.2 Chemical Modifications

1. Functionalization: Functionalizing nanoparticles with biocompatible molecules, such as PEG or amino acids, can reduce toxicity.

2. Surface charge modification: Modifying the surface charge of nanoparticles can reduce toxicity. For example, neutral or negatively charged particles may be less toxic than positively charged particles.

3. Chemical conjugation: Conjugating nanoparticles with biocompatible molecules, such as peptides or antibodies, can reduce toxicity.

6.3 Formulation Modifications

1. Encapsulation: Encapsulating nanoparticles in liposomes or other biocompatible carriers can reduce toxicity.

2. Emulsification: Emulsifying nanoparticles in oil-in-water or water-in-oil emulsions can reduce toxicity.

3. Suspension: Suspending nanoparticles in biocompatible solvents, such as water or glycerin, can reduce toxicity.

6.4 Testing and Evaluation

1. In vitro testing: Testing nanoparticles in vitro using cell cultures or other biological systems can help identify potential toxicity.

2. In vivo testing: Testing nanoparticles in vivo using animal models can help evaluate their safety and efficacy.

3. Clinical trials: Conducting clinical trials can help evaluate the safety and efficacy of nanoparticles in humans.

6.5 Regulatory Compliance

1. FDA guidelines: Following FDA guidelines for the development and testing of nanoparticles can help ensure their safety and efficacy.

2. EU regulations: Complying with EU regulations for the development and testing of nanoparticles can help ensure their safety and efficacy.

3. ISO standards: Following ISO standards for the development and testing of nanoparticles can help ensure their safety and efficacy.       

6.0 CONCLUSION:

The use of nanoparticles in beauty and skincare offers numerous benefits, from improving the stability and efficacy of active ingredients to enhancing the safety and sensory experience of the products. These innovations not only improve consumer satisfaction but also open new avenues for treating complex skin issues more effectively. These advanced materials have some benefits, while their utilization in cosmetic formulation it may associated with some risk. The main aim of this dissertation work is highlight the benefits and risk of the nanomaterials used in the cosmetic products.

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