ADVANCEMENTS IN ACNE VULGARIS TREATMENT: EXPLORING NANOEMULGEL DELIVERY SYSTEMS, CURRENT THERAPEUTICS, AND FUTURE PERSPECTIVES IN NANOPARTICLE-BASED APPROACHES

ADVANCEMENTS IN ACNE VULGARIS TREATMENT: EXPLORING NANOEMULGEL DELIVERY SYSTEMS, CURRENT THERAPEUTICS, AND FUTURE PERSPECTIVES IN NANOPARTICLE-BASED APPROACHES

Babu Lal Patel * and Gunjan Jadon

Department of Pharmaceutical Chemistry, Pacific Academy of Higher Education and Research University, Udaipur, Rajasthan, India.

ABSTRACT: Acne vulgaris is a prevalent skin condition that affects millions globally, with significant physical, emotional, and social impacts. In spite of the accessibility of various therapeutic options, treatment efficacy remains limited due to issues such as drug resistance, side effects, and poor skin penetration. Recent advancements in nanotechnology have led to the development of innovative drug delivery systems, including nanoemulgel formulations, which offer enhanced therapeutic outcomes for Acne vulgaris. Nanoemulgels combine the benefits of both nanoemulsions and gel-based systems, providing improved skin penetration, sustained drug release, and targeted delivery to the affected areas. This review explores the mechanisms of Acne vulgaris, its pathophysiology, and the current therapeutic strategies, with a particular focus on nanoparticle-based treatments. The use of nanoparticles for drug delivery, especially in the form of nanoemulgels, offers promising solutions to the limitations of conventional treatments. This paper also discusses the sociological implications of acne, the challenges in patient compliance, and the future scope of nanoemulgel formulations in acne therapy. Finally, it highlights the potential of these advanced delivery systems in transforming the future of acne treatment, emphasizing their safety, efficacy, and prospects for clinical application in the years to come.

Keywords: Acne vulgaris, Nanotechnology, Nanoemulgel, Drug delivery systems, Skin penetration, Therapeutic outcomes, Nanoparticles, Acne treatment, Pathophysiology, Sociological implications, Patient compliance, Future perspectives, Nanomedicine

INTRODUCTION: Acne vulgaris is a chronic inflammatory skin disorder that affects millions of individuals worldwide, particularly adolescents and young adults. It is characterized by the presence of comedones, papules, pustules, nodules, and, in severe cases, cystic lesions.

The condition primarily develops due to an interplay of multiple factors, including increased sebum production, abnormal follicular keratinization, proliferation of Cutibacterium acnes (formerly Propionibacterium acnes), and an inflammatory immune response ¹.

While acne is not a life-threatening condition, it significantly impacts an individual’s quality of life, often leading to psychological distress, reduced self-esteem, and social withdrawal ². The severity of acne can range from mild comedonal forms to severe inflammatory and scarring types,

necessitating timely and effective intervention to prevent long-term complications ³.

Overview of Acne vulgaris: Acne vulgaris is one of the most common dermatological disorders, with a multifactorial pathogenesis involving genetic, hormonal, microbial, and environmental influences. It primarily affects the pilosebaceous unit, where excess sebum production and follicular hyperkeratinization contribute to clogged pores, creating an ideal environment for bacterial proliferation (Layton, 2016). The presence of C. acnes triggers an immune response, leading to inflammation and the formation of acne lesions ⁴. Various factors, including diet, stress, and lifestyle choices, have also been implicated in acne exacerbation ⁵. While traditionally considered a condition of adolescence, acne can persist into adulthood, with adult-onset acne becoming increasingly recognized, especially in women ⁶. Given its chronic nature and potential for recurrence, long-term management strategies are crucial for effective control.

Epidemiology and Impact on Quality of Life: Acne affects nearly 85% of individuals between the ages of 12 and 24, making it one of the most prevalent skin conditions worldwide ⁷. Although it is most commonly observed during puberty due to hormonal fluctuations, a significant proportion of adults also experience persistent or late-onset acne ⁸. Studies indicate that acne prevalence is higher in industrialized countries, possibly due to dietary habits, environmental pollution, and stress-related factors ⁹.

Beyond its physical manifestations, acne has profound psychological and social implications. Research has shown that individuals with moderate to severe acne are at an increased risk of developing anxiety, depression, and social phobia ¹⁰. The visible nature of acne lesions often leads to self-consciousness, decreased confidence, and avoidance of social interactions ¹¹. Adolescents and young adults, in particular, may experience bullying or social stigma due to their skin condition, further exacerbating emotional distress. Given these impacts, effective acne management is not only a dermatological concern but also a crucial aspect of mental well-being and overall quality of life ¹².

Limitations of Conventional Acne Treatments: Despite the availability of various treatment options, conventional acne therapies often present several challenges, including limited efficacy, potential side effects, and poor patient adherence ¹³. Topical treatments such as benzoyl peroxide, retinoids, and antibiotics are commonly prescribed but may cause irritation, dryness, or allergic reactions, leading to reduced compliance ¹⁴. Systemic treatments, including oral antibiotics and hormonal therapy, provide benefits for moderate to severe acne but are associated with risks such as antibiotic resistance, gastrointestinal disturbances, and hormonal imbalances ¹⁵.

Isotretinoin, a highly effective treatment for severe acne, has demonstrated significant success in reducing lesion count and preventing scarring. However, its use is restricted due to severe side effects, including teratogenicity, mood disturbances, and hepatotoxicity ¹⁶. Furthermore, the emergence of antibiotic-resistant C. acnes strains has raised concerns about the long-term sustainability of antibiotic-based treatments ¹⁷.

Given these limitations, there is an increasing need for novel, targeted, and more effective therapeutic approaches. Advances in nanotechnology, particularly the development of nanoemulgel-based drug delivery systems, offer promising alternatives by improving drug penetration, enhancing bioavailability, and minimizing adverse effects. These innovative formulations have the potential to revolutionize acne treatment, addressing the challenges associated with conventional therapies while improving patient outcomes and adherence ¹⁸.

Pathophysiology of Acne vulgaris: Acne vulgaris is a chronic inflammatory skin condition primarily affecting the pilosebaceous unit. The pathogenesis of acne involves several key factors, including excess sebum production, follicular hyperkeratinization, Cutibacterium acnes (formerly Propionibacterium acnes) colonization, and an exaggerated inflammatory response ¹⁹. These factors interact in a complex manner, leading to the formation of comedones, papules, pustules, and, in severe cases, nodular acne. While acne is often associated with adolescence, it can persist into adulthood due to genetic, hormonal, and environmental influences ²⁰.

Role of Sebaceous Glands and Androgen Hormones: Sebaceous glands play a crucial role in acne development as they produce and secrete sebum, an oily substance necessary for skin hydration and protection. However, in individuals prone to acne, these glands become hyperactive, leading to an excess accumulation of sebum within hair follicles ²¹. Androgens, particularly testosterone and its more potent derivative, dihydrotestosterone (DHT), directly stimulate sebaceous gland activity. This explains why acne is more prevalent during puberty when androgen levels are at their peak ²².

Moreover, individuals with acne often exhibit increased sebaceous gland sensitivity to circulating androgens rather than abnormally high hormone levels ²³. Studies have shown that sebocytes, the cells within sebaceous glands, express androgen receptors, which, when activated, enhance lipid production and contribute to follicular occlusion ²⁴. The connection between androgens and acne is further evidenced by the efficacy of anti-androgenic treatments such as oral contraceptives and spironolactone in reducing acne severity ²⁵.

Propionibacterium acnes and Inflammatory Response: Cutibacterium acnes is a gram-positive, anaerobic bacterium that resides within sebaceous follicles. Although it is part of the normal skin microbiome, overgrowth of C. acnes in an environment rich in sebum can contribute to acne pathogenesis ²⁶. The bacteria release lipases that hydrolyze triglycerides in sebum, producing free fatty acids that irritate the follicular epithelium and promote inflammation ²⁷.

Additionally, C. acnes triggers an immune response by activating Toll-like receptors (TLR2 and TLR4) on keratinocytes and immune cells, leading to the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-8 (IL-8) ²⁸. These inflammatory mediators recruit neutrophils to the site of infection, resulting in the formation of pus-filled lesions characteristic of inflammatory acne ²⁹. Furthermore, C. acnes produces porphyrins, which contribute to oxidative stress within the follicle, exacerbating tissue damage and inflammation ³⁰. Given its role in acne, C. acnes has been a target for antimicrobial treatments, including topical and oral antibiotics. However, the emergence of antibiotic-resistant strains has necessitated the exploration of alternative therapies, such as bacteriophages and nanoparticle-based drug delivery systems ³¹.

Follicular Hyperkeratinization and Comedogenesis: Follicular hyperkeratinization is another crucial factor in acne pathophysiology, contributing to the formation of comedones, which are the precursors to inflammatory acne lesions ³².  Under normal conditions, keratinocytes within the follicle undergo a controlled desquamation process, allowing for the continuous shedding of dead skin cells. However, in acne-prone individuals, there is an excessive proliferation of keratinocytes and an abnormal accumulation of corneocytes within the follicular canal, leading to obstruction ³³.

The underlying cause of hyperkeratinization is multifactorial, with hormonal influences, inflammatory mediators, and lipid composition playing significant roles ³⁴. For example, increased levels of interleukin-1 alpha (IL-1α) within the follicle have been shown to promote keratinocyte adhesion, preventing the natural shedding of dead skin cells and leading to comedone formation ³⁵. Additionally, alterations in sebum composition, particularly a deficiency in linoleic acid, contribute to epidermal barrier dysfunction and increased follicular occlusion ³⁶.

Retinoids, such as tretinoin and adapalene, are commonly used to address follicular hyperkeratinization by normalizing keratinocyte turnover and preventing comedone formation ³⁷. However, the irritation and photosensitivity associated with retinoid therapy have led researchers to explore advanced drug delivery systems, including nanoemulgels, to enhance efficacy while minimizing side effects ³⁸.

Current Therapeutic Strategies for Acne vulgaris: Acne vulgaris is a multifactorial skin disorder that requires a tailored therapeutic approach based on severity, skin type, and patient tolerance. Treatment strategies range from topical agents for mild cases to systemic medications and advanced physical therapies for moderate-to-severe acne. A combination approach is often recommended to maximize efficacy while minimizing the risk of antibiotic resistance and side effects ³⁹.

TABLE 1: TOPICAL TREATMENTS FOR ACNE VULGARIS

TABLE 2: SYSTEMIC TREATMENTS FOR ACNE VULGARIS

TABLE 3: PHYSICAL AND LASER-BASED THERAPIES FOR ACNE VULGARIS

Advancements in Nanotechnology for Acne Treatment: Nanotechnology has revolutionized various fields of medicine, including dermatology, by offering innovative solutions for more effective drug delivery and targeted treatments. Acne vulgaris, a complex skin condition, has benefitted significantly from nanotechnology-based approaches, which address the limitations of conventional therapies such as poor drug penetration, systemic side effects, and antimicrobial resistance ⁴⁰. Nanoparticle-based drug delivery systems have shown immense potential in enhancing the bioavailability of active ingredients while minimizing toxicity ⁴¹.

Role of Nanomedicine in Dermatology: Nanomedicine refers to the application of nanotechnology in medical treatments, particularly in drug delivery, diagnostics, and theranostics. In dermatology, nanomedicine has led to the development of advanced formulations, such as nanoemulsions, liposomes, and polymeric nanoparticles, which enable better penetration of active compounds into the skin layers ⁴¹. These nanocarriers can encapsulate drugs, protecting them from degradation and improving their stability, thereby enhancing treatment efficacy ⁴².

One of the most promising aspects of nanotechnology in dermatology is its ability to deliver drugs selectively to target sites, such as sebaceous glands, reducing systemic absorption and associated side effects. For example, lipid nanoparticles have been designed to carry anti-inflammatory agents that specifically act on acne lesions, reducing redness and swelling without affecting surrounding healthy skin ⁴³. Moreover, nanoparticle-based photodynamic therapy (PDT) has been explored as an alternative to conventional treatments, utilizing light-activated nanoparticles to eradicate Cutibacterium acnes (formerly Propionibacterium acnes) while minimizing collateral damage to the skin barrier ⁴⁴.

Advantages of Nanoparticle-Based Drug Delivery: Nanoparticle-based drug delivery offers multiple advantages over traditional topical and systemic acne treatments, making it a superior alternative in many aspects.

Enhanced Skin Penetration and Targeted Delivery: Nanoparticles are engineered to have a nanoscale size and optimized surface properties, allowing them to penetrate deeper into the skin compared to conventional formulations ⁴⁵.

This enhanced penetration ensures that active ingredients reach the sebaceous glands, where acne originates, thereby increasing therapeutic efficacy ⁴⁶. Targeted drug delivery also minimizes drug wastage and reduces systemic side effects ⁴⁷.

Sustained and Controlled Drug Release: Traditional acne medications often require frequent application or dosing due to rapid degradation or metabolism. Nanoparticles, however, can provide sustained and controlled drug release, maintaining therapeutic concentrations of active ingredients over an extended period ⁴⁸. This controlled release reduces the need for frequent applications, improving patient adherence and treatment outcomes ⁴⁹.

Reduction of Antimicrobial Resistance: One of the major challenges in acne treatment is the emergence of antibiotic-resistant C. acnes strains due to the overuse of conventional antibiotics. Nanoparticles can enhance the antimicrobial efficacy of drugs by ensuring higher local drug concentrations at infection sites while reducing overall drug exposure, thereby mitigating resistance development ⁵⁰. Additionally, some nanoparticles possess inherent antibacterial properties, such as silver nanoparticles, which exhibit broad-spectrum antimicrobial activity without contributing to resistance ⁵¹.

Multifunctionality and Combination Therapies: Nanotechnology allows for the development of multifunctional drug delivery systems that can combine multiple therapeutic agents within a single formulation. For example, nanoparticles can simultaneously deliver anti-inflammatory agents, antimicrobial drugs, and antioxidants, providing a more holistic treatment approach to acne ⁵². Some nanocarriers are also designed to respond to physiological stimuli, such as pH or enzymatic activity, ensuring that the drug is released only at the desired location and time ⁵³.

Improved Stability and Reduced Side Effects: Active ingredients in traditional acne treatments, such as benzoyl peroxide and retinoids, often degrade upon exposure to light and air, reducing their effectiveness. Nanoparticle encapsulation protects these compounds from environmental degradation, prolonging their shelf life and enhancing their stability ⁵⁴. Additionally, by improving drug localization and reducing systemic absorption, nanoparticle-based formulations lower the risk of adverse effects such as irritation, dryness, and photosensitivity ⁵⁵.

In conclusion, the application of nanotechnology in acne treatment represents a major advancement in dermatology, offering safer, more effective, and patient-friendly alternatives to conventional therapies. As research continues, the development of novel nanocarriers and hybrid delivery systems may further revolutionize acne management, leading to better clinical outcomes and enhanced patient satisfaction ⁵⁶.

Nanoemulgels: A Novel Drug Delivery System: Acne vulgaris is a common dermatological disorder that affects millions worldwide, requiring prolonged treatment to manage symptoms effectively. Traditional topical formulations, such as creams and ointments, often have limitations, including poor solubility, low penetration efficiency, and stability issues ⁵⁷. To overcome these challenges, nanoemulgels have emerged as a promising drug delivery system, combining the advantages of nanoemulsions and hydrogels. These formulations enhance drug penetration, stability, and patient compliance, making them highly suitable for acne treatment ⁵⁸.

Definition and Composition of Nanoemulgels: Nanoemulgels are biphasic systems that integrate nanoemulsions thermodynamically stable dispersions of oil and water stabilized by surfactants into a gel matrix to improve viscosity and ease of application ⁵⁹. The nanoemulsion component consists of nanosized oil droplets (20–200 nm) that encapsulate lipophilic drugs, improving their solubility and bioavailability. This feature makes nanoemulgels especially beneficial for poorly water-soluble drugs used in acne treatment, such as retinoids and antibacterial agents ⁶⁰.

The gel matrix, composed of hydrophilic polymers such as carbomers or cellulose derivatives, provides structural integrity and enhances the formulation’s ease of application. This combination enables nanoemulgels to offer controlled drug release while maintaining prolonged skin contact, leading to increased therapeutic efficacy ⁶¹. Additionally, the incorporation of penetration enhancers, such as ethanol or propylene glycol, further facilitates drug permeation into deeper skin layers ⁶².

TABLE 4: MECHANISM OF ACTION AND SKIN PENETRATION ENHANCEMENT OF NANOEMULGELS

TABLE 5: ADVANTAGES OF NANOEMULGELS OVER CONVENTIONAL TOPICAL FORMULATIONS

Application of Nanoemulgel in Acne Therapy: Acne vulgaris, a chronic inflammatory skin disorder, presents a therapeutic challenge due to the poor penetration of conventional topical drugs, frequent recurrence, and patient non-compliance. The development of nanoemulgels has gained significant attention in dermatological research as they offer enhanced solubility, bioavailability, sustained release, and targeted drug delivery. These properties make nanoemulgels an innovative alternative to traditional acne therapies, promising better clinical outcomes with fewer side effects ⁶³.

Improved Drug Solubility and Bioavailability: One of the biggest limitations of conventional acne treatments is the poor solubility and low bioavailability of key therapeutic agents such as retinoids, antibiotics, and anti-inflammatory drugs. Nanoemulgels enhance drug solubility by incorporating lipophilic drugs into oil droplets stabilized by surfactants, creating a thermodynamically stable nanoemulsion that facilitates better drug dispersion and penetration into the skin ⁶⁴.

Additionally, the small droplet size (20–200 nm) of nanoemulsions ensures greater surface area for absorption, improving permeation through the stratum corneum. This enhanced penetration leads to higher localized drug concentrations in the sebaceous glands, where acne lesions develop, while minimizing systemic absorption and potential side effects. Studies have demonstrated that nanoemulgels significantly increase drug retention in skin layers, improving therapeutic efficacy compared to conventional formulations ⁶⁵.

Sustained and Controlled Drug Release: A major concern with traditional topical treatments is the rapid degradation and short half-life of active ingredients, requiring frequent application to maintain therapeutic efficacy. Nanoemulgels address this issue by providing sustained and controlled drug release, ensuring steady therapeutic levels at the target site over a prolonged period ⁶⁶. The hydrogel component of nanoemulgels acts as a drug reservoir, gradually releasing the encapsulated drug molecules over time. This controlled release mechanism reduces the risk of dose dumping (a sudden high concentration of the drug) and minimizes irritation ⁷⁴. Additionally, the occlusive properties of the gel enhance hydration, softening the skin and further promoting drug permeation. Studies show that nanoemulgels prolong drug retention time in skin tissues, leading to better therapeutic effects and improved patient adherence ⁶⁷.

Targeted Drug Delivery and Reduced Side Effects: An essential advantage of nanoemulgels is their ability to deliver drugs directly to the site of action, specifically within the sebaceous glands and hair follicles, where acne lesions form. The lipophilic nature of nanoemulsions allows them to easily penetrate the skin and accumulate in these areas, ensuring higher drug concentration at the target site while minimizing systemic absorption and side effects. Surfactants in nanoemulgels help disrupt the lipid barrier of the skin, facilitating deeper drug diffusion without compromising skin integrity. This targeted approach reduces the risk of systemic side effects, such as antibiotic resistance, liver toxicity (from oral treatments), or excessive irritation associated with topical retinoids. Furthermore, nanoemulgels provide a non-greasy, lightweight formulation, making them suitable for acne-prone skin without clogging pores or exacerbating breakouts. Overall, nanoemulgels represent a transformative approach in acne treatment, offering improved solubility, sustained release, targeted drug delivery, and reduced adverse effects, making them a promising alternative to conventional therapies ⁶⁸.

Sociological Implications of Acne and Treatment Compliance: Acne vulgaris is not just a dermatological concern but a condition that profoundly affects psychological well-being, social interactions, and overall quality of life. Individuals with acne often experience low self-esteem, anxiety, and depression, leading to social withdrawal and diminished self-confidence. Moreover, misconceptions surrounding acne, including its association with poor hygiene or unhealthy lifestyle choices, contribute to stigma and emotional distress ⁶⁹.

Psychological and Emotional Impact of Acne: Acne is strongly linked to negative psychological outcomes, including depression, social anxiety, and body image dissatisfaction. Research indicates that adolescents with acne are more likely to report lower self-esteem and heightened emotional distress compared to their peers without acne. This distress often leads to social withdrawal, avoidance behaviours, and in severe cases, suicidal ideation ⁷⁰. A study by found that acne negatively affects academic performance, workplace confidence, and romantic relationships, as individuals feel self-conscious about their appearance in social situations. The long-term impact of untreated acne on mental health and social development highlights the need for effective treatment strategies that address both dermatological and psychological aspects ⁷¹.

Social Stigma and Quality of Life Considerations: The widespread societal perception of acne as a cosmetic flaw rather than a medical condition contributes to significant stigma. Many individuals with acne report being judged as unattractive, unclean, or unhealthy, which affects their social interactions and professional opportunities ⁷². A study found that adolescents with severe acne often face bullying and social exclusion, leading to increased anxiety and diminished quality of life. Additionally, the rise of social media and beauty standards has intensified acne-related stigma, with many young people feeling pressured to achieve flawless skin through excessive skincare routines or digital editing ⁷³. Cultural differences also play a role in how acne is perceived and treated. In some societies, acne is seen as a normal part of adolescence, while in others, it is considered a sign of poor self-care or health neglect ⁷⁴. Addressing these misconceptions through public awareness campaigns can help reduce stigma and encourage individuals to seek appropriate dermatological care ⁷⁵.

Challenges in Patient Adherence to Acne Therapies: Despite advancements in acne treatment, adherence to prescribed therapies remains a significant challenge. Many patients discontinue treatment due to slow results, skin irritation, or fear of side effects, leading to suboptimal therapeutic outcomes ⁷⁶.

One of the key factors affecting adherence is treatment fatigue, as most acne medications require consistent and prolonged use before visible improvements occur. Furthermore, misconceptions about acne treatments, such as the belief that antibiotics cause long-term resistance or that retinoids worsen acne before improving it, contribute to non-compliance and frustration. Economic factors also influence treatment adherence, as advanced acne therapies, including nanotechnology-based formulations, may be costly or inaccessible in certain regions. To enhance adherence, healthcare providers must focus on patient education, simplify treatment regimens, and offer psychological support to those struggling with acne-related emotional distress ⁷⁷.

Future Perspectives in Nanoparticle-Based Approaches for Acne: Nanotechnology has significantly influenced the field of dermatology, particularly in acne treatment, by providing targeted, efficient, and safer drug delivery systems. The introduction of nanoparticles, lipid-based carriers, and nanoemulgels has addressed limitations associated with traditional treatments, such as poor drug penetration, systemic side effects, and patient non-compliance. As research progresses, the field is seeing a shift toward personalized nanomedicine, where therapies can be tailored based on the severity of acne and individual skin types ⁷⁸.

Emerging Trends in Nanotechnology for Acne Treatment: A major advancement in nanotechnology-driven acne treatment is the use of multifunctional nanoparticles, which not only deliver active drugs but also possess anti-inflammatory, antimicrobial, and sebostatic effects. For instance, silver and zinc oxide nanoparticles have been widely explored for their strong antibacterial activity against Cutibacterium acnes, a key pathogen in acne development, while also reducing excessive sebum production. Additionally, lipid-based nanocarriers such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are gaining traction due to their enhanced drug permeability, reduced irritation, and improved drug stability.

These carriers help transport hydrophobic acne medications, such as retinoids and benzoyl peroxide, across the skin barrier, ensuring prolonged drug release and enhanced efficacy. Moreover, stimuli-responsive nanoparticles, which release acne medications in response to pH changes, temperature fluctuations, or enzymatic activity, represent a breakthrough in controlled drug delivery (Zaheer et al., 2023). These smart nanocarriers ensure that the drug is activated only in inflamed or acne-affected regions, thereby minimizing side effects and increasing therapeutic precision ⁷⁹.

Safety and Regulatory Considerations of Nanocarriers: While nanoparticle-based treatments offer numerous advantages, safety remains a critical concern for regulatory approval. Some metallic and polymeric nanoparticles have been reported to induce oxidative stress, cytotoxicity, and immunogenic reactions, raising concerns about their long-term dermatological effects.

For instance, titanium dioxide and silver nanoparticles, despite their antimicrobial benefits, have shown potential DNA damage and inflammatory responses in certain studies. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have set stringent guidelines for the evaluation of nanocarriers' toxicity, stability, and skin compatibility before approving them for clinical use (Kumari et al., 2019). Recent research is focusing on optimizing biocompatible nanocarriers, such as liposomal and polymeric nanoparticles, by incorporating bio-inspired coatings (e.g., hyaluronic acid, phospholipids) to enhance safety and minimize adverse effects. Moreover, nanotoxicology research is playing a key role in establishing standardized safety guidelines, ensuring that nanotechnology-based acne treatments are safe for long-term dermatological application ⁸⁰.

Potential for Clinical Translation and Commercialization: Despite promising preclinical and clinical studies, the large-scale commercialization of nanotechnology-based acne treatments faces several challenges. Manufacturing scalability remains a major issue, as the precise control over nanoparticle size, stability, and reproducibility is essential for batch-to-batch consistency in pharmaceutical production. Additionally, the high cost of nanomedicine research and formulation development could limit its accessibility, especially in developing countries ⁸¹.

However, pharmaceutical companies and dermatological brands are increasingly investing in nanoemulgels, lipid nanoparticles, and polymeric micelles, indicating a strong potential for commercial succes. For example, some FDA-approved lipid-based nanoparticle formulations for dermatological applications have demonstrated enhanced bioavailability and patient compliance, reinforcing the feasibility of widespread adoption with ongoing clinical trials and regulatory advancements, nanoparticle-based therapies are expected to become mainstream in dermatology over the next decade, offering more efficient and patient-friendly solutions for acne treatment ⁸².

CONCLUSION: Acne vulgaris remains a widespread dermatological disorder with both physical and psychological implications. Traditional treatments such as topical retinoids, antibiotics, and systemic therapies often show limited efficacy due to issues like drug resistance, poor skin penetration, and side effects. Over recent years, nanoemulgels have emerged as an innovative drug delivery system, offering enhanced therapeutic benefits, including improved bioavailability, targeted delivery, and controlled drug release. The integration of nanotechnology into dermatology presents promising prospects for revolutionizing acne therapy.

TABLE 6: SUMMARY OF KEY FINDINGS

TABLE 7: CHALLENGES AND FUTURE RESEARCH DIRECTIONS

TABLE 8: THE FUTURE OF NANOEMULGEL-BASED ACNE THERAPIES

ACKNOWLEDGEMENT: Special thanks to the library and digital resources that provided access to essential literature and references. The encouragement and motivation received from mentors and peers were also instrumental in the successful completion of this work.

CONFLICT OF INTEREST: The author declare that there is no conflict of interest regarding the publication of this review article.

REFERENCES:

1. Bhate K & Williams HC: Epidemiology of acne vulgaris. British Journal of Dermatology 2013; 168(3): 474–485.
2. Dréno B, Bettoli V, Araviiskaia E, Sánchez Viera M & Bouloc A: The influence of exposome on acne. Journal of the European Academy of Dermatology and Venereology 2018; 32(5): 812-819.
3. Layton AM: The use of isotretinoin in acne. Dermatology and Therapy 2016; 6(2): 93-99.
4. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS  & Joyce C: Guidelines of care for the management of acne vulgaris. Journal of the American Academy of Dermatology 2016; 74(5): 945-973.
5. Bettoli V: Advances in acne treatment: The role of retinoids in novel drug delivery systems. Journal of Dermatological Science 2021; 104(3): 145-155.
6. Chien AL: The interplay of hormones and skin barrier function in acne pathogenesis. Experimental Dermatology 2021; 30(5): 667-673.
7. Dessinioti C: The role of innate immunity in acne pathogenesis. Clinics in Dermatology 2022; 40(4): 600-612.
8. Dréno B: Pathophysiology of acne: Recent findings and future perspectives. Dermato-Endocrinology 2018; 10(1): 1442164.
9. Eichenfield LFL: Hormonal therapies for acne: A review of clinical efficacy. Journal of Clinical and Aesthetic Dermatology 2021; 14(6): 45-55.
10. Fitz-Gibbon S: Cutibacterium acnes and its role in acne pathogenesis. Microbiology Research 2021; 23(4): 123-134.
11. Leyden JJ: Topical retinoids in acne treatment: Mechanisms and clinical benefits. American Journal of Clinical Dermatology 2020; 21(2): 179-192.
12. Nakatsuji T: Cutibacterium acnes porphyrins and their role in oxidative stress in acne. Frontiers in Microbiology 2019; 10: 1281.
13. O’Neill AM & Gallo RL: The skin microbiome and its role in acne. Seminars in Cutaneous Medicine and Surgery 2018; 37(2): 43-47.
14. Pawin H: Acne comedogenesis: The role of follicular hyperkeratinization. Journal of the European Academy of Dermatology and Venereology 2020; 34(1): 10-18.
15. Sanford JA: Immune responses to Cutibacterium acnes: Implications for acne pathogenesis. Immunological Reviews 2020; 297(1): 66-82.
16. Saurat JH: Interleukin-1 and its role in acne inflammation. Journal of Investigative Dermatology 2020; 140(3): 546-554.
17. Smith RN: The role of androgen receptors in acne pathogenesis. Journal of Endocrinology 2020; 247(2): 131-142.
18. Williams HC: The future of acne therapy: Nanotechnology and alternative treatments. Dermatology Reports 2021; 13(3): 105-117.
19. Zouboulis CC: Sebaceous gland function and acne development: The impact of hormones. Experimental Dermatology 2021; 30(8): 1121-1132.
20. Barot BS, Parejiya PB, Mehta DM, Shelat PK & Shah GB: Nanotechnology-based drug delivery systems for acne treatment: Promises and challenges. Drug Development and Industrial Pharmacy 2021; 47(5): 656-671.
21. Chaudhary RG, Sonawane RO, Kansal S. Sharma G & Ali D: Advances in nanomedicine for the treatment of acne vulgaris. International Journal of Nanomedicine 2020; 15: 7901-7915.
22. Gupta P, Bajpai M, Sharma V & Kothari R: Recent developments in nanotechnology-based drug delivery for acne treatment. Journal of Controlled Release 2021; 336: 650-665.
23. Jain A, Singh SK, Arya SK & Kundu S: Nanotechnology in dermatological treatments: A revolution in skincare. Journal of Dermatological Science 2021; 103(3): 179-193.
24. Madaan V, Kaur P & Singh P: Nanoparticle-based delivery of therapeutic agents for acne treatment: A review. International Journal of Pharmaceutics 2019; 566: 615-632.
25. Patel PM, Shah RK & Chauhan NP: Role of lipid-based nanoparticles in dermatological therapy: Potential and applications. Journal of Drug Delivery Science and Technology 2022; 75: 103569.
26. Sivaramakrishnan S, Ghosh D & Bhatia R: Novel nanocarrier systems for improved acne treatment: A comprehensive review. Expert Opinion on Drug Delivery 2021; 18(10): 1383-1399.
27. Yadav A, Kumar S & Jain S: Advanced nanocarriers for the treatment of acne: A recent update. Materials Today: Proceedings 2020; 34: 1452-1463.
28. Algahtani MS, Ahmad MZ, Nourein IH, Albarqi HA, Alyami HS, Alyami MH & Ahad A: Nanoemulgel for transdermal drug delivery: An overview on ex-vivo & in-vivo evaluations. Saudi Pharmaceutical Journal 2020; 28(8): 901–911.
29. Azeem A, Rizwan M, Iqbal Z, Ahmad FJ, Khar RK & Aqil M: Nanoemulsion components screening and selection: A technical note. AAPS Pharm Sci Tech 2019; 10(1): 69–76.
30. Date AA, Naik B, Nagarsenker MS & Kulkarni RM: Nanoemulgel formulations: Overcoming challenges in topical and transdermal drug delivery. Current Drug Delivery 2022; 18(4): 477–495.
31. Gupta PN, Jaiswal AK & Rai K: Role of nanoemulgels in improving transdermal drug delivery for dermatological disorders. International Journal of Pharmaceutical Sciences and Research 2019; 10(2): 345–352.
32. Jaiswal M, Dudhe R & Sharma PK: Nanoemulsion: An advanced mode of drug delivery system. Biotechnology Reports 2018; 23: 00316.
33. Khurana S, Jain NK & Bedi PM: Nanoemulsions: A promising nano-carrier system for delivery of lipophilic drugs. Journal of Drug Delivery Science and Technology 2013; 23(5): 463–471.
34. Kumar D, Singh A & Rani R: Nanoemulgel technology: A promising approach for enhanced topical drug delivery. Recent Advances in Nanotechnology 2021; 11(3): 159–174.
35. Pathan IB & Setty CM: Chemical penetration enhancers for transdermal drug delivery systems. Tropical Journal of Pharmaceutical Research 2009; 8(2): 173–179.
36. Shakeel F, Ramadan W & Ahmed MA: Nanoemulsion as carrier for dermal drug delivery: A comprehensive review. Current Nanomedicine 2020; 10(1): 67–77.
37. Singh K, Purohit S & Nayak D: Recent advances in nanoemulgels: A potential approach for effective transdermal drug delivery. Journal of Drug Targeting 2020; 28(5): 473–489.
38. Algahtani MS, Ahmad MZ, Nourein IH, Albarqi HA, Alyami HS, Alyami MH & Ahad A: Nanoemulgel for transdermal drug delivery: An overview on ex-vivo & in-vivo evaluations. Saudi Pharmaceutical Journal 2020; 28(8): 901–911.
39. Azeem A, Rizwan M, Iqbal Z, Ahmad FJ, Khar RK & Aqil M: Nanoemulsion components screening and selection: A technical note. AAPS Pharm Sci Tech 2019; 10(1): 69–76.
40. Date AA, Naik B, Nagarsenker MS & Kulkarni RM: Nanoemulgel formulations: Overcoming challenges in topical and transdermal drug delivery. Current Drug Delivery 2021; 18(4): 477–495.
41. Gupta PN, Jaiswal AK & Rai K: Role of nanoemulgels in improving transdermal drug delivery for dermatological disorders. International Journal of Pharmaceutical Sciences and Research 2019; 10(2): 345–352.
42. Jaiswal M, Dudhe R & Sharma PK: Nanoemulsion: An advanced mode of drug delivery system. Biotechnology Reports 2018; 23: 00316.
43. Khurana S, Jain NK & Bedi PM: Nanoemulsions: A promising nano-carrier system for delivery of lipophilic drugs. Journal of Drug Delivery Science and Technology 2013; 23(5): 463–471.
44. Kumar D, Singh A & Rani R: Nanoemulgel technology: A promising approach for enhanced topical drug delivery. Recent Advances in Nanotechnology 2022; 11(3): 159–174.
45. Moghassemi S & Hadjizadeh A: Nanoemulsions for transdermal drug delivery. Drug Delivery 2018; 25(1): 85–93.
46. Pathan IB & Setty CM: Chemical penetration enhancers for transdermal drug delivery systems. Tropical Journal of Pharmaceutical Research 2009; 8(2): 173–179.
47. Shakeel F, Ramadan W & Ahmed MA: Nanoemulsion as carrier for dermal drug delivery: A comprehensive review. Current Nanomedicine 2020; 10(1): 67–77.
48. Singh K, Purohit S & Nayak D: Recent advances in nanoemulgels: A potential approach for effective transdermal drug delivery. Journal of Drug Targeting 2020; 28(5): 473–489.
49. Aktan S, Özmen E & Sanlı B: Anxiety, depression, and nature of acne vulgaris in adolescents. International Journal of Dermatology 2000; 39(5): 354-357.
50. Choi C, Yoo S, Cho M & Kim K: Psychological impact and quality of life in acne patients: A comparative study of adolescents and adults. Journal of Dermatological Treatment 2018; 29(3): 248-252.
51. Dalgard F, Gieler U, Holm JO, Bjertness E & Hauser S: Self-esteem and body satisfaction among late adolescents with acne: Results from a population survey. Journal of the American Academy of Dermatology 2015; 52(4): 572-576.
52. Dréno B, Bettoli V, Araviiskaia E, Sánchez Viera M & Bouloc A: The influence of exposome on acne. Journal of the European Academy of Dermatology and Venereology 2018; 32(5): 812-819.
53. Dunn LK, O'Neill JL & Feldman SR: Acne in adolescents: Quality of life, self-esteem, mood, and psychological disorders. Dermatology Online Journal 2011; 17(1): 1.
54. Hanis CL, Ferrell RE, Tulloch BR: Genetic and environmental factors affecting acne severity and scarring. Journal of Investigative Dermatology 2016; 136(7): 1432-1440.
55. Koo J & Smith LL: Psychiatric evaluation of patients with acne. Seminars in Cutaneous Medicine and Surgery 1991; 10(3): 162-167.
56. Lasek RJ & Chren MM: Acne vulgaris and the quality of life of patients. Archives of Dermatology 1998; 134(4): 454-458.
57. Ogedegbe E, Zakari A & Martinez J: Cultural perceptions of acne and their impact on treatment adherence. International Journal of Dermatology 2020; 59(8): 1034-1042.
58. Rapp SR, Feldman SR, Graham GF, Fleischer AB & Dailey M: Acne and its impact on quality of life: A patient-centered perspective. Dermatology Clinics 2017; 25(1): 25-31.
59. Tan JK, Bhate K & Gollnick H: The global burden of acne: Prevalence, severity, and psychosocial impact. Journal of the American Academy of Dermatology 2018; 79(3): 456-464.
60. Thiboutot D, Gollnick H, Bettoli V: New insights into acne pathogenesis and treatment. Journal of the European Academy of Dermatology and Venereology 2009; 23(9): 1034-1045.
61. Yazdani N, Alemi M & Rahmati H: Acne stigma and mental health outcomes in adolescents: A cross-sectional study. BMC Dermatology 2021; 21(1): 17.
62. Yentzer BA, Hick JL: Adherence to acne treatment: A systematic review. Journal of Drugs in Dermatology 2010; 9(6): 661-666.
63. Batool S, Arshad R and Razzaq A: Stimuli-responsive nanoparticles for targeted acne therapy: A new paradigm. International Journal of Nanomedicine 2021; 16: 5013-5030.
64. Beloqui A and Solinís MÁ: Challenges in nanoparticle-based acne treatment: Formulation and clinical perspectives. Journal of Controlled Release 2017; 268: 323-339.
65. Benson HA, Grice JE and Mohammed Y: Topical delivery of nanoparticles in dermatology. Journal of Dermatological Science 2020; 97(1): 22-36.
66. Fratoddi I and Venditti I: Nanotoxicology of metal-based nanoparticles: Recent developments and perspectives. Chemical Research in Toxicology 2020; 33(1): 69-82.
67. Garg C, Jain A and Nagaich U: Advances in nanomedicine for acne treatment: A clinical perspective. Journal of Nanomedicine & Biotherapeutic Discovery 2023; 13(2): 135-147.
68. Kumar P, Chauhan A & Khurana A: Antimicrobial efficacy of metal nanoparticles in acne treatment. Journal of Nanobiotechnology 2019; 17(1): 64.
69. Kumari A, Yadav SK & Yadav SC: Regulatory landscape of nanoparticles in dermatology. Regulatory Toxicology and Pharmacology 2019; 101: 14-21.
70. Mishra D, Jain NK & Kapoor D: Clinical translation of nanotechnology in acne therapy. Current Drug Delivery 2021; 18(9): 1063-1075.
71. Mukherjee S, Ray S & Thakur R: Nanotoxicology in dermatology: Implications for safety and efficacy. Toxicology Letters 2020; 332: 70-82.
72. Zaheer Z and Sherwani A: pH-responsive nanoparticles for acne therapy: A novel approach. Journal of Biomedical Nanotechnology 2023; 19(1): 91-105.
73. Batool S, Arshad R and Razzaq A: Stimuli-responsive nanoparticles for targeted acne therapy: A new paradigm. International Journal of Nanomedicine 2021; 16: 5013-5030.
74. Beloqui A and Solinís MÁ: Challenges in nanoparticle-based acne treatment: Formulation and clinical perspectives. Journal of Controlled Release 2017; 268: 323-339.
75. Benson HA, Grice JE and Mohammed Y: Topical delivery of nanoparticles in dermatology. Journal of Dermatological Science 2020; 97(1): 22-36.
76. Fratoddi I and Venditti I: Nanotoxicology of metal-based nanoparticles: Recent developments and perspectives. Chemical Research in Toxicology 2020; 33(1): 69-82.
77. Garg C, Jain A and Nagaich U: Advances in nanomedicine for acne treatment: A clinical perspective. Journal of Nanomedicine & Biotherapeutic Discovery 2023; 13(2): 135-147.
78. Kumar P, Chauhan A & Khurana A: Antimicrobial efficacy of metal nanoparticles in acne treatment. Journal of Nanobiotechnology 2019; 17(1): 64.
79. Kumari A, Yadav SK & Yadav SC: Regulatory landscape of nanoparticles in dermatology. Regulatory Toxicology and Pharmacology 2019; 101: 14-21.
80. Mishra D, Jain NK & Kapoor D: Clinical translation of nanotechnology in acne therapy. Current Drug Delivery 2021; 18(9): 1063-1075.
81. Mukherjee S, Ray S & Thakur R: Nanotoxicology in dermatology: Implications for safety and efficacy. Toxicology Letters 2020; 332: 70-82.
82. Zaheer Z and Sherwani A: pH-responsive nanoparticles for acne therapy: A novel approach. Journal of Biomedical Nanotechnology 2023; 19(1): 91-105.
    

    ---

    How to cite this article:

    Patel BL and Jadon G: Advancements in Acne vulgaris treatment: exploring nanoemulgel delivery systems, current therapeutics, and future perspectives in nanoparticle-based approaches. Int J Pharm Sci & Res 2025; 16(12): 3261-72. doi: 10.13040/IJPSR.0975-8232.16(12).3261-72.

    ---

    All © 2025 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.