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15 October 2024

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Unveiling New Horizons: Advancing Technologies in Cosmeceuticals for Anti-Aging Solutions

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Department of Pharmacy, University of Sorocaba (UNISO), Sorocaba 18023-000, Brazil
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Molecules2024, 29(20), 4890;https://doi.org/10.3390/molecules29204890
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Abstract

In the last years, the landscape of anti-aging cosmetics has been marked by significant advances in cosmeceutical delivery systems. This study aimed to conduct a systematic review of these technological innovations, with a focus on anti-aging effects, from 2018 to 2023. The methodology included a thorough search on PubMed and through gray literature, applying rigorous exclusion criteria. The descriptors were selected based on the Medical Subject Headings (MeSH). A total of 265 articles were found. Exclusion criteria were applied, and 90 of them were selected for full reading. After reading the full 90 articles, 52 were excluded, leaving 38 articles for final evaluation composing this review. The key findings highlighted a clear prevalence of studies exploring nanotechnology, including nanoparticles, niosomes, and liposomes. Most of the formulations analyzed in this review emphasize antioxidant activities, which play a crucial role in preventing premature aging caused by free radicals. The reviewed studies revealed specific activities, such as the reduction in melanin synthesis, the inhibition of enzymes involved in the skin aging process, and the prevention of morphological changes typical of aging.

1. Introduction

In recent years, the continuous improvement in living standards, along with environmental degradation, has sparked growing interest in methods to prevent or delay skin aging, particularly photoaging. In 2017, the global cosmetics market reached USD 532.43 billion, and is projected to reach 805.61 billion by 2023, demonstrating a compound annual growth rate (CAGR) of 7.14% from 2018 to 2023 [1].
The cosmetics industry uses the term ‘cosmeceutical’ to describe products that claim to impact skin health or have a lasting effect on skin appearance [2]. These formulations are described by the industry as containing therapeutically active ingredients, specifically developed to have reparative effects when applied topically, in addition to their traditional cosmetic use. According to industry claims, these formulations imply a physiological or pharmacological action. Cosmeceuticals are known by various names, such as dermatocosmetics, functional cosmetics, bioactives, and dermocosmetics, among others [3]. Cosmeceuticals serve as a bridge between pharmaceutical preparations and specialized personal care products [4].
Common age-related disorders include wrinkles, reduced skin elasticity, and hyperpigmentation. Wrinkles are a prevalent indicator of human skin aging, resulting from decreased production of collagen and elastin—vital proteins for skin strength and resilience [5]. The decline in skin elasticity with age is largely attributed to the reduction in the production of these proteins. As collagen levels decrease, the skin becomes more susceptible to wrinkles, sagging, and loss of a youthful appearance. This process is further accelerated by external factors such as sun exposure and pollution, which generate reactive oxygen species (ROS) that degrade collagen and impair its production. Additionally, hormonal changes, especially during menopause, exacerbate this reduction in skin elasticity [6].
Currently, the perception of skin health and beauty is associated with overall well-being, leading to a growing demand for anti-aging products. Although no topical treatment or ingredient has been shown to completely halt photoaging, literature reviews suggest that some products may reduce and delay the signs associated with this process. Ingredients such as retinoids, antioxidants, and sunscreens have been identified in research as effective in mitigating the effects of photoaging and promoting skin health [7].
In the current landscape, the demand for cosmetics that offer deeper and longer-lasting results is strongly driven by innovations. There is an increasing emphasis on investigating the stability and enhanced efficacy of active ingredients [8]. Significant advances in drug delivery systems have been the subject of research, including the development of new encapsulation strategies to effectively protect and transport active ingredients. Researchers have also focused on manipulating the release timing of the active principle, which refers to controlling how quickly the active ingredient is released at the target area. Additionally, targeted delivery techniques are being explored to direct drugs specifically to the intended site of action, enhancing efficacy and reducing side effects [9].
The efficacy of a cosmetic depends not only on the active ingredients but also on the technology used in its formulation. The primary function of the vehicle is to efficiently deliver the active ingredients to the desired location and ensure that they remain there long enough to produce the intended effect [10]. In this context, the use of nanoparticles has been widely explored by the cosmetics industry. Nanoparticles are small particles with dimensions measured in nanometers, typically ranging from 1 to 100 nanometers. Due to their reduced size, they exhibit unique physical, chemical, and biological properties compared to bulk materials, making them useful in various fields, including medicine, cosmetics, and electronics [11].
Nanotechnology aims to enhance various characteristics such as durability, water resistance, strength, and conductivity. Nanomaterials are increasingly being selected for their ability to overcome common limitations in cosmetics, such as penetration, stability, and controlled release of active ingredients [12].
The development of these nanotechnology-based products includes a variety of nanomaterials with distinct compositions, sizes, and shapes, with nanocarriers being one of the most common examples. The essential function of nanocarriers is to transport and deliver bioactive agents to target tissues; they can be made from various materials with different structures. Their primary characteristic is particle size, which plays a crucial role, as it directly influences the biological properties of the carrier [13]. Complementing this approach, nanoemulsions emerge as a promising example of nanocarriers, offering advantages such as transparency, low viscosity, and high efficiency in penetrating active ingredients—characteristics that make them ideal for cosmetic applications [14].
In this context, nanotechnology has found applications in the field of cosmetics, giving rise to innovative formulations known as nano-cosmeceuticals. These include nanoformulated cosmetics using polymer-based nanostructured systems (such as nanocapsules and nanosheres), lipid-based nanostructured systems (such as liposomes, niosomes, and nanoemulsions), and metal-based nanostructured systems (such as gold and silver nanoparticles), among others. Each of these has specific characteristic properties that enhance drug delivery, increase absorption, potentiate cosmetic efficacy, and offer many other benefits [8,15].
Although the unique properties of nanomaterials make them desirable for cosmetic applications, as they can perform specific functions, they may also pose health risks to consumers. The potential health risks associated with insoluble nanoparticles are a widely debated topic in the scientific literature, primarily due to conflicting results and the lack of long-term toxicological studies [16]. Therefore, to determine whether a nanomaterial is safe for human health and the environment, a range of parameters must be assessed, with particular emphasis on advanced physicochemical characterizations [17].
There is still no global consensus on the definition of nanomaterials as cosmetic ingredients. As a result, each country adopts its own definition and regulation. The United States and the European Union are the two largest cosmetic markets [18]. The EU, in its Regulation EC 1223/2009, defines nanomaterial as ‘an insoluble or biopersistent material intentionally manufactured with one or more external dimensions, or an internal structure, in the size range of 1 to 100 nm’. In the United States, the FDA (Food and Drug Administration) has yet to adopt an official definition for nanomaterials. However, in 2014, the agency highlighted two criteria for assessing whether a regulated product involves the application of nanotechnology: (1) whether ‘a material or final product is designed to have at least one external dimension, or an internal or surface structure, in the nanoscale range (approximately 1 nm to 100 nm)’; and (2) whether ‘a material or final product is designed to exhibit properties or phenomena, including physical or chemical properties or biological effects, attributable to its size, even if those dimensions exceed the nanoscale, up to one micrometer (1000 nm)’ [19].
Understanding these delivery systems with potential anti-aging effects is necessary to elucidate the latest cosmeceutical technologies aimed at delaying or minimizing the risk of skin aging. The objective of this study was to systematically review the technological advancements in cosmeceutical delivery systems over the past five years, focusing on anti-aging effects.

2. Results

Review Methodology: Article Selection and Analysis

For this review, only articles related to delivery systems focused on anti-aging cosmetics for topical use were considered. Figure 1 illustrates the search process carried out in the PubMed database and gray literature, in which 265 articles were identified. Of these, 135 were excluded after reading the titles, as they were either reviews or indicated in the title that the study addressed injectable or subcutaneous substances. After this initial exclusion stage, 130 articles remained, 2 of which were discarded for not being freely available in full, resulting in 128 articles for the next screening phase. Of the 128 articles, 38 were excluded after reading the abstracts, as they did not fit the theme of the review. The remaining 90 articles were read in full, and from this total, 52 were eliminated for not focusing on anti-aging solutions. Thus, 38 articles were included in the final evaluation that supports this review.
Figure 1. Establishment of exclusion criteria and the leaving articles.
After the completion of the final article selection, the results were organized into three tables to provide a clearer visualization of the outcomes. In Table 1, there are in vitro and ex vivo studies; in Table 2, there are in vivo studies (conducted on animals); and in Table 3, there are human studies (clinical trials). Only two studies addressed ex vivo were grouped in the same table as in vitro studies. Each table presents the main outcome of the study, the delivery system used, the active compound, along with the corresponding reference.
Table 1. Summary of data collected from in vitro studies on new cosmeceuticals delivery systems selected by the exclusion criteria mentioned above.
Table 2. Summary of data collected from in vivo studies on new cosmeceuticals delivery systems selected by the exclusion criteria mentioned above.
Table 3. Summary of data collected from clinical studies on new cosmeceuticals delivery systems selected by the exclusion criteria mentioned above.
Table 1 presents the results of the selected in vitro studies, which involve experiments conducted outside living organisms, generally microorganisms, cells, or molecules extracted from their normal biological context. The use of in vitro techniques is essential for the advancement of scientific knowledge, providing a solid experimental foundation for the interpretation and application of results obtained in more complex biological models.
The selection of articles for in vitro analysis comprised 17 publications that met the predefined criteria. Among these, a prevalence was observed in articles featuring delivery systems based on nanoparticles, followed by those employing niosomes and liposomes as release systems. In only one article found, ethosomes and transetosomes were used as a release system, which have similar characteristics to liposomes and niosomes.
Table 2 presents the results of in vivo studies, with the majority of rats and mice being used to carry out skin contact or compound diffusion tests. In vivo studies refer to experimental protocols using animals, conducted after approval of the research by a respective ethics committee. In this review, analyzes were carried out through the topical application of the developed formulations. Articles that met the predefined inclusion criteria totaled 10, including articles covering in vitro and animal tests. The predominance of nanotechnology through the delivery of nanoparticle assets is observed in eight studies. Additionally, there are two studies that use micelles and emulgel as their delivery modes. The observed results present confirmed anti-aging actions and a positive result on each delivery system.
Table 3 presents the results of the studies in humans. Human studies refer to clinical trials conducted in a selected population, after research approval by an ethics committee. This type of research corresponds to the final phase of testing for the delivery of new products. In this review paper, clinical trials were conducted through the topical application of the developed formulations. The papers that met the predefined inclusion criteria totaled 10, including papers encompassing in vitro, animal, and human trials described only in this table. The predominance of nanotechnology through the delivery of nanoparticulate actives is observed with five articles, followed by two microparticulate actives. Additionally, there are three articles in which the particle size is unknown as the article does not mention it. The results obtained through the formulations indicate anti-aging action in all studies selected in this review, with anti-wrinkle action and skin hydration being the most observed results.
Table 4 presents the cosmeceutical delivery systems found in this review, with the main ones being lipid-based nanosystems—liposomes, niosomes, solid lipid nanoparticles (SLNs), nanoemulsions—and metal-based nanosystems—metallic nanoparticles. The delivery systems differ in physical and chemical properties, but a significant trend of utilizing nanotechnology is noticeable in the majority of the selected studies. It has become evident that the use of nanotechnology in cosmetics is becoming a crucial tool for scientific investigation as well as the development of new cosmetic products. It was remarkable to observe that, in cosmetic formulations, a considerable amount of nanoscale materials is already being introduced or recommended for future use, both as nanosystems and as new nanocarriers designed to encapsulate active ingredients. This aims to facilitate their effective delivery through the skin barriers.
Table 4. Summaries of data collected about cosmeceutical delivery system.
In the in vitro studies analyzed in Table 5, significant gaps were identified regarding the limitations of the work, particularly concerning the long-term effects and practical applicability of these technologies. For example, some studies demonstrated the administration of compounds through delivery systems based on niosomes, highlighting their anti-aging activity but failing to delve into the mechanisms of action of the active principles [20]. Similarly, another article explored the immediate effects of pre-treatment against UV stress without considering the cumulative impacts over time, which are essential for understanding the total effect on skin aging [21]. The lack of data on long-term efficacy emerged as a recurring theme. In one study, the incubation effects were limited to short periods (48 to 72 h), with no evaluations that considered prolonged impacts [23]. In another study, funded by Inoliva Ilac ve Gida A.S., the authors did not present data assessing the long-term anti-aging effects of the formulations and did not discuss potential conflicts of interest, a crucial aspect for ensuring research transparency [22]. Furthermore, limitations were observed in quantification methods [24] and in the measurement of a restricted number of inflammatory response markers [25]. The stability of some delivery systems also raised questions, as they require stringent storage conditions to maintain their properties [26]. This concern is compounded by the inherent instability and easy degradation of certain compounds, such as ascorbic acid [28]. Additionally, the studies lack data on adverse environmental conditions, such as light exposure and humidity, which represent a significant obstacle to the practical application of the formulations [34,36]. The absence of long-term safety tests [29,32,33] and results from delivery systems that did not provide information on skin penetration and the lasting effects of topical application were also noted [31]. In summary, although the reviewed studies demonstrate promising advancements in the use of innovative delivery systems in cosmeceuticals, most still need to investigate long-term effects and the practical applicability of these formulations in the context of skin aging and other cosmetic applications.
Table 5. Limitations of in vitro studies, system stability, and delivery system ingredients.
The analysis of the limitations found in in vivo studies (Table 6) revealed several gaps that may impact the interpretation and applicability of the results. Several works [37,38,42,43,44] exhibit deficiencies in critical information, such as the age of the animals used and the number of individuals tested [38]. The absence of details regarding age may compromise the validity of the results, as the developmental stage of the animals is fundamental in evaluating biological responses. The lack of robust stability tests is a recurring limitation. Studies 38 and 47 did not provide information on the conduct of stability tests, while study 41 did not mention long-term tests under varying temperature and humidity conditions. Furthermore, study 39 highlighted the physical instability of emulsions containing L-ascorbic acid, suggesting that the formulation may not be reliable. This gap in methodology could undermine the effectiveness of the formulations in the long term. In studies 40 and 45, adult rats aged between six and eight weeks were used; however, the methodology did not clarify whether these animals were in an appropriate phase for anti-aging investigations. The lack of clarity regarding the conditions of induced aging in the animals limits the applicability of the findings in broader contexts. Study 47 revealed size-dependent toxicity of nanoparticles but did not explore the underlying mechanisms of this phenomenon. In summary, the identified limitations, including the absence of information on the age of the animals, the lack of stability tests, and insufficient characterization of the mechanisms of action, indicate the need for a more rigorous and detailed approach in future investigations.
Table 6. Limitations of in vivo studies, system stability, and delivery system ingredients.
The clinical studies presented in Table 7 analyzed the efficacy of anti-aging products, revealing several limitations. Some studies included potentially harmful ingredients in the tested formulations, such as parabens, which may impact the safety and acceptability of the products [48,52,57]. Furthermore, many studies had a limited number of participants; for example, one study had only 13 healthy Asian women aged between 25 and 40, which may not adequately represent the efficacy of the product in older age groups—a crucial factor for anti-aging products [49]. Another point to consider is that some studies were conducted using a single-blind methodology [49,50] and in single centers [49,50,52], further compromising the robustness of the results. In contrast, the presence of conditions like melasma among the participants was considered an advantage in assessing the treatment’s efficacy [50]. In one study, the sample consisted of only six healthy volunteers, all with normal skin, which compromised the generalization of the results due to the small and unrepresentative sample size [51]. Moreover, another study focused on specific age groups, such as the anti-aging mask tested on individuals aged 42 to 64 and the purifying mask on participants aged 25 to 40, allowing for a more targeted evaluation; however, the small sample size still limited generalization [56]. Finally, the research involving healthy men also had limitations, with only 13 participants, and the conclusion was generic, highlighting promising effects without providing specific evidence regarding the efficacy of the tested products [57]. Overall, the main limitations identified were the small number of volunteers, inadequate or unreported age, and lack of information about the quality of the volunteers’ skin. Additionally, some studies provided generic conclusions, emphasizing promising anti-aging effects from topical application without delivering specific evidence of the efficacy of the tested product [52,53,57]. Only in one of the studies, compared with the others, no significant limitations were observed [55].
Table 7. Limitations of clinical studies, system stability, and delivery system ingredients.

3. Discussion

Cosmetics are an indispensable element of daily routines. Moreover, the incorporation of nanotechnology into cosmetics has heightened its widespread acceptance among users globally. As evidenced by the presented outcomes, innovative nanocarriers such as liposomes, nanoemulsions, niosomes, lipid nanoparticles, polymeric nanoparticles, microparticles, etc., are employed in the formulation of diverse cosmetics and cosmeceuticals, leading to enhanced results. The review highlights the prevalence of nanoformulations, indicating a notable advantage in integrating nanocomponents into cosmetic products. This advantage includes the improvement of stability for inherently unstable cosmetic ingredients in formulations, increased permeability of specific active ingredients, improved effectiveness and tolerance of UV absorbers, and an overall enhancement in aesthetic appeal of the products [3]. According to Bilal et al. [1], these nano systems can assist in the absorption or penetration of active portions of cosmeceuticals into the epidermal layers in a remarkable way, achieving either a burst or sustained release of active ingredients.
The delivery systems differ in physical and chemical properties, and the main ones found in this review are liposomes, niosomes, solid lipid nanoparticles (SLNs), nanoemulsions, and metallic nanoparticles. Liposomes (LP) are biodegradable vesicles consisting of a spherical phospholipid bilayer enclosing an aqueous compartment. The most commonly used lipids in LP preparations include phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, sphingolipids, glycolipids, and sterols. LP come in diameters ranging from 20 nm up to a few hundred micrometers [58]. They can be categorized as either unilamellar or multilamellar vesicles. Both hydrophilic and lipophilic ingredients can be encapsulated into LP within the polar and oil-soluble cavities, respectively [59].
Niosomes are vesicles composed of non-ionic surfactants—amphipathic compounds with an overall neutral charge. These structures are analogous to phospholipid vesicles, such as LP, demonstrating the capability to encapsulate aqueous solutes and function as carriers for drugs. The cost-effectiveness, enhanced stability, and consequent ease of storage associated with non-ionic surfactants have prompted their utilization as viable substitutes for phospholipids [60]. Solid lipid nanoparticles are considered colloidal delivery systems and represent innovative delivery systems consisting of a monolayer shell encapsulating a lipid core and finding application in the formulation of cosmeceuticals. These formulations feature a solid-state lipid matrix with a nanometer size [61].
Nanoemulsions are liquid dispersions considered to be kinetically or thermodynamically stable, where an oil phase and an aqueous phase are combined with a surfactant. Depending on the composition, nanoemulsions can be categorized as oil-in-water, water-in-oil, or bicontinuous. The particle sizes in these nanoemulsions range from 50 to 200 nm. These dispersed phases contain small particles or droplets with very low oil/water interfacial tension. Nanoemulsions have a lipophilic core surrounded by a monomolecular layer of phospholipids, making them particularly suitable for delivering lipophilic compounds [62].
Among the metallic nanoparticles, gold, silver, zinc oxide, and titanium oxide are highlighted. Gold nanoparticles have gained prominence in cosmetic formulations due to their effectiveness against bacterial and fungal infections. These particles range in diameter from 1 to 100 nm. Various biological activities are achieved through the use of gold nanoparticles, including rubefacient effects, enhancement of skin metabolism, and the slowing down of aging symptoms [63]. Similar to gold nanoparticles, silver nanoparticles also exhibit remarkable activity against bacteria and fungi. Formulating these nanoparticles into skin ointments provides additional benefits as a disinfectant, and they are also used in oral cosmeceuticals [64].
Zinc oxide (ZnO) nanoparticles are widely used in cosmetics, sun care products, coatings, and antibacterial products. In addition to their ability to block UVA and UVB rays, these nanoparticles are incorporated into various cosmetic formulations to protect against the long-term harmful effects of these rays, such as skin aging and skin cancer [65]. Titanium dioxide (TiO2) nanoparticles are included in various cosmetic products as UV filters. Titanium dioxide primarily functions by reflecting UVB radiation. Thus, the combined use of TiO2 and ZnO nanoparticles provides excellent protection against solar radiation without causing the skin irritation often associated with chemical UV filters [66].
In our investigation, we noted a wide array of active ingredients, emphasizing the diverse approaches employed in the development of anti-aging products. Each component brings unique benefits, contributing to a more comprehensive strategy in alleviating skin tissue damage. The literature reviewed reveals a diversity of natural ingredients, including gallic acid, Myrtus communis extract, glutathione tripeptide, Ocimum sanctum extract, lycopene, royal jelly, epigallocatechin gallate (EGCG), resveratrol, myricetin, ascorbic acid (AA), nicotinamide (NIC), morin, bakuchiol, and curcumin. These extracts generally offer therapeutic benefits or drug-like properties capable of influencing the biological functions of the skin based on their constituents [20,27,28,50,51]. They represent comprehensive skincare solutions that go beyond mere aesthetic improvement, contributing to enhanced skin function and appearance. These ingredients stimulate collagen production, combat the harmful effects of free radicals, maintain keratin integrity under challenging conditions, and promote healthier skin.
A majority of the formulations identified in this review highlight antioxidant activities, crucial in preventing premature aging induced by free radicals. Oxidative stress is considered a significant mechanism in skin aging, triggering the apoptosis of many cell types, especially human skin fibroblast cells, crucial for maintaining youthful and healthy skin [5,7,32,36,43]. The ability to neutralize free radicals is essential to protect the skin against oxidative damage. The specific activities identified in the studies of this review, such as melanin reduction, inhibition of enzymes related to skin aging, and prevention of morphological changes associated with aging, point to promising results.
These targeted actions contribute to a more holistic approach to reducing the signs of aging. Features such as biocompatibility, non-cytotoxicity, and long-term stability emphasize the importance of developing products that are safe for topical use. These attributes are essential for ensuring the acceptance and effectiveness of anti-aging products. Although the results are promising, it is important to recognize potential challenges, such as the stability of certain ingredients.
Most of the formulations highlighted in the studies demonstrated effectiveness in addressing signs of aging, ranging from wrinkle reduction to increased hydration, enhanced elasticity, and diminished spots. Several articles highlight that their formulations outperform conventional treatments, such as chemical peels, indicating a potential breakthrough in the field. The observation of clinical and visual improvements, such as the recovery of skin damaged by UV radiation and visible anti-wrinkle effects, strengthens the practical applicability of these formulations. The studies demonstrate improvements in the skin’s ultrastructure and suggest that some formulations have effects beyond the surface, potentially influencing deeper cellular processes.
According to the findings, in in vitro studies, the efficacy of various formulations is highlighted, including niosomes with gallic acid, NanoPCL-M nanofibers with natural extract of Myrtus communis, propolis polyphenols delivery systems, NLC with O. sanctum extract, and systems containing lycopene, morin, GA–AuNPs, among others. These formulations demonstrate antioxidant activities, inhibition of enzymes related to aging, protection against oxidative stress, and other beneficial effects. Human studies assessed specific formulations, including those that provide anti-aging action, recovery of the skin from imperfections related to sun exposure, effective treatment for melasma, visible improvements in wrinkles and skin texture, and increased skin hydration, elasticity, and smoothness.
Certain ingredients, such as gallic acid, glutathione tripeptide, O. sanctum extract, EGCG, resveratrol, myricetin, morin, CA (telomerase activator), GA–AuNPs, bakuchiol, curcumin, propolis, adenosine, niacinamide, and sulforaphane, are featured in both in vitro and in vivo tables, indicating anti-aging activities, such as wrinkle reduction, improvements in skin hydration and elasticity, and protection against oxidative stress. This suggests a consistent exploration of promising anti-aging compounds from the laboratory settings to human trials. The correlation between in vitro and human studies suggests a positive transition from laboratory results to clinically observable benefits.
Delivery systems, such as niosomes, nanofibers, lipids, nanoemulsions, and nanocomposites, have proven effective in both scenarios, emphasizing the importance of suitable delivery systems to optimize the absorption and efficacy of active ingredients. Some formulations, such as the antioxidant efficacy of GA–AuNPs and the reduction in melanin by SLNs containing EGCG, resveratrol, and myricetin, can be directly compared.
Additional findings reveal that some formulations showed visible improvements in the short term, while others, such as “anti-aging masks” and “lifting” treatments, demonstrated longer-term benefits, implying different treatment durations for specific outcomes. However, it is important to emphasize that these observations provide an overview of the progression from in vitro to clinical studies. Careful consideration of experimental conditions, as well as the limitations and inherent variabilities in each system is essential for a comprehensive understanding.
Nanomaterials such as liposomes, nanoparticles, and nanoemulsions can enhance the penetration of active ingredients into the skin, allowing for more controlled and targeted release. This results in greater bioavailability, improving efficacy with lower doses. While conventional formulations are widely effective, particularly in anti-aging treatments and acne management, they may encounter absorption limitations, with effects concentrated in the more superficial layers of the skin [67].
The cosmetics industry claims that nanotechnology can minimize adverse effects by enabling the controlled release of actives in smaller doses. However, there are concerns regarding the long-term release of nanoparticles, which may penetrate biological barriers and enter systemic circulation. In contrast, conventional substances such as retinoids are known to cause irritation, redness, and peeling, especially in sensitive skin, although their long-term safety is well documented [68].
Cosmetic products based on nanotechnology tend to be more expensive due to advanced manufacturing processes and the research required to develop safe and effective formulations. This can raise the final price for consumers, whereas conventional formulations are widely available and more affordable due to large-scale production and greater standardization of use [69].
Conventional formulations, particularly retinoic acid, are highly unstable when exposed to air and light, which can reduce their efficacy over time if not stored properly. On the other hand, nanoparticles can enhance the stability of active ingredients that normally degrade quickly when exposed to air or light, prolonging the shelf life of products [70].
Due to their sustained release capability of active ingredients into the skin, nanotechnology products allow the actives to act for extended periods, reducing the need for frequent reapplication. In contrast, conventional products generally have a more immediate and superficial release, which can lead to localized concentration peaks, increasing the risk of irritation [71].
This review noted that the cosmetics industry claims nanotechnology provides significant advancements, particularly in efficacy, precise release, and safety with lower doses. However, concerns about its long-term impact and higher costs remain. In contrast, conventional products continue to be a reliable choice due to their affordability and well-established safety profile, despite potential side effects.
The data analysis reveals that, although the evaluated studies offer promising advances in the application of innovative delivery systems in cosmeceuticals, various methodological and long-term limitations compromise the robustness and applicability of the results. In the in vitro studies, there was a lack of investigations into the mechanisms of action of the active ingredients, as well as the absence of evaluations of cumulative long-term effects. These factors are essential for understanding the long-lasting efficacy of anti-aging cosmeceuticals, as skin aging is a continuous and multifactorial process. Additionally, the lack of data on formulation stability and the impact of environmental conditions, such as light and humidity, raises questions about the practical viability of these technologies for end consumers. The stability of compounds like ascorbic acid, known for its easy degradation, is a crucial example that highlights the need for greater efforts to ensure the efficacy of products over time.
In vivo and clinical studies also present limitations such as small sample sizes, lack of age diversity among participants, and the absence of long-term stability tests, all of which emerge as significant issues. The presence of potentially harmful ingredients in some tested formulations, such as parabens, and the use of simple methodologies, such as single-blind studies conducted in single centers, reduce the reliability of the results. The lack of clarity regarding the conditions of induced aging in animals and insufficient information on size-dependent nanoparticle toxicity further indicate that greater rigor is needed in future investigations. In summary, while innovative delivery systems show great potential, there is a clear need for more comprehensive studies that consider long-term effects, formulation stability, and participant profile diversity to ensure effective practical translation.
Finally, we observe that several countries are dedicated to the study and development of new anti-aging cosmetics and active delivery methods. This review highlights significant contributions from researchers in Egypt (six articles), Portugal, Italy, and Iran (with n = three each), Taiwan, Thailand, Pakistan, Greece, and China (with n = two each), and Turkey, Poland, Japan, Indonesia, France, Spain, Korea, Canada, and Saudi Arabia, with one article each. This global collaboration of researchers reflects the diversity and international commitment to advancing anti-aging science. These findings indicate a combination of factors that may contribute to a growing interest in skin aging research, such as climate and environmental conditions of intense sun exposure. Climatic characteristics may trigger the need to develop specific solutions to protect and treat the skin, and as awareness of skincare grows, researchers may be responding to this demand by working on the development of more effective products.
In conclusion, the thorough investigation into diverse delivery systems and active ingredients in anti-aging formulations reveals a dynamic landscape in the cosmeceutical field. Innovations in active delivery methods demonstrate promising progress in the quest for effective and safe solutions to combat signs of skin aging. The widespread use of nanotechnology, exemplified by liposomes, nanoparticles, and niosomes, marks a significant advancement. The transition from in vitro studies to human trials indicates a promising continuity, with nanocarriers demonstrating significant anti-aging effects. Improvements in skin hydration, elasticity, and reduction in wrinkles, along with the sustained benefits of long-term treatments, offer a holistic perspective on the potential of these nanoformulations. While challenges in ingredient stability remain, the remarkable progress in addressing oxidative stress and other aging-related factors through nanotechnology suggests a future where cutting-edge cosmeceuticals, leveraging nanocarriers, will play a crucial role in promoting skin health. This review contributes to the ongoing dialogue in the field, emphasizing the importance of targeted, effective, and safe nanotechnology-based anti-aging solutions that meet the evolving demands of skincare.

4. Materials and Methods

Systematic electronic research was conducted on two search platforms (PubMed and gray literature) on 24 August 2023. The combined descriptors used as search a strategy in the literature are shown in Figure 2. The descriptors were selected based on the ’Medical Subject Headings (MeSH),’ and they were selected to be sufficiently specific, avoiding the inclusion of overly broad or irrelevant literature.
Figure 2. Descriptor combinations overview, based on the ‘Medical Subject Headings (MeSH).
The research was conducted over a five-year period, from 2018 to 2023, and focused solely on the English language. Only original articles related to delivery systems focusing on anti-ageing cosmetics for topical use were considered for this review.
As shown in Figure 3, exclusion criteria included articles not addressing the proposed topic, duplicates, review articles, articles on subcutaneous or injectable applications, and articles not available in full. The final selection was restricted to works related to delivery systems for cosmetic formulations with anti-aging effects.
Figure 3. Exclusion criteria selection process leading to analyzed articles.
To conduct a meticulous article selection, five evaluators participated in all stages of the process. At each subsequent phase, the articles were randomly redistributed among the evaluators to ensure the reliability of the results.

Author Contributions

Conceptualization: D.G. and Y.O.-F.; methodology: P.L.M.A., V.N., F.d.C.M., E.C. and J.d.S.; software: P.L.M.A.; formal analysis: D.G. and Y.O.-F.; writing—original draft preparation: P.L.M.A., V.N., F.d.C.M., E.C. and J.d.S.; writing—review and editing: P.L.M.A.; supervision, D.G. and Y.O.-F. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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