Formulation and Characterization of a Polyherbal Nanogel for Acne Management

Skin diseases constitute a significant burden on global health, particularly among adolescents and young adults. Among these, acne vulgaris is one of the most prevalent chronic inflammatory dermatoses, affecting approximately 85–90% of adolescents globally [1]. This condition is primarily a disorder of the pilosebaceous unit, characterized by comedones, inflammatory papules, pustules, nodules, and in severe cases, cystic lesions and scarring. The etiopathogenesis of acne involves a multifactorial process, including excessive sebum production, hyperkeratinization, colonization by Cutibacterium acnes (formerly Propionibacterium acnes), and subsequent inflammatory responses [2]. Additionally, hormonal fluctuations, especially during puberty, and environmental factors such as pollution and humidity can aggravate the condition. Several synthetic therapeutic agents are currently available for acne management, including benzoyl peroxide, retinoids, antibiotics (clindamycin, erythromycin), salicylic acid, and azelaic acid. While efficacious, prolonged use of these agents often leads to adverse effects such as skin irritation, dryness, photosensitivity, and most critically, the emergence of antibiotic resistance [3]. Given these challenges, there has been a paradigm shift toward herbal and polyherbal formulations for dermatological applications. Herbal remedies are often considered safer and better tolerated due to their biocompatibility and reduced side effects, thereby fostering increased consumer acceptance [4]. The potential of herbal extracts to mitigate acne symptoms lies in their anti-inflammatory, antimicrobial, antioxidant, and sebum-regulating properties. Notable botanicals include:

Turmeric (Curcuma longa): Possesses potent anti-inflammatory and antibacterial activity via its active component curcumin [5].

Neem (Azadirachta indica): Demonstrates broad-spectrum antimicrobial and anti-inflammatory effects [6].

Tea tree oil (Melaleuca alternifolia): Rich in terpinen-4-ol, tea tree oil has been clinically shown to reduce acne lesions due to its bactericidal action [7].

Orange peel (Citrus sinensis) and Lemon juice (Citrus limon): Provide vitamin C, flavonoids, and natural AHAs that contribute to skin exfoliation and oil control [8].

Honey (Apis mellifera): Offers hydrating and antibacterial properties that support skin healing [9].

Despite the promising therapeutic potential of herbal agents, their clinical efficacy is often hampered by poor skin permeability, instability, and inconsistent bioavailability. Nanotechnology, particularly nanogel systems, has emerged as an effective strategy to overcome these limitations. Nanogels are hydrogel particles in the nanometer size range, offering controlled drug release, enhanced skin penetration, targeted delivery, and stability of phytoconstituents [10]. They also improve patient compliance due to their non-greasy, transparent, and spreadable nature. This study aims to develop a polyherbal anti-acne nanogel combining the synergistic effects of five botanicals—turmeric, neem, tea tree oil, orange peel extract, and honey—embedded in a guar gum-based gel matrix. Guar gum, a natural polysaccharide, was selected for its biocompatibility, film-forming, and gelling properties [11]. The rationale behind polyherbalism is multitargeted therapy, where various herbs contribute complementary actions, enhancing the overall therapeutic effect while minimizing side effects. Moreover, the use of ethanol as a solvent in the extraction process facilitates the solubilization of bioactive components, improving stability and dispersion in the gel matrix [6]. This research seeks to bridge a critical gap in acne therapeutics by formulating and evaluating a novel polyherbal anti-acne nanogel that is both safe and effective. The study focuses on a thorough physicochemical evaluation of the developed nanogel, aiming to ensure its functionality, stability, and therapeutic efficiency. To achieve this, the formulation undergoes a comprehensive assessment of its organoleptic properties, which includes careful observation and analysis of its color, odor, and greasiness. These characteristics are vital not only for quality control but also for user acceptability, as they directly influence consumer preference and compliance. A formulation that is visually appealing, non-greasy, and pleasantly scented stands a better chance of being adopted in both clinical and commercial settings [12]. In addition to sensory characteristics, the nanogel is evaluated for its pH and viscosity. The pH of the formulation must align closely with the natural pH of human skin to avoid irritation or disruption of the skin barrier. Viscosity is another crucial parameter that affects the application, spreadability, and retention of the gel on the skin’s surface. A product that is too fluid may not remain on the target site long enough to be effective, whereas one that is too thick may hinder absorption and be uncomfortable for the user [13]. The spreadability and washability of the nanogel are also rigorously examined. Spreadability reflects how easily the gel can be applied across the skin without requiring excessive force, thus enhancing user experience and ensuring uniform distribution of active ingredients. Washability pertains to how easily the formulation can be removed from the skin, which is particularly important for products intended for repeated daily use. A formulation that is easy to rinse off without leaving residue enhances user satisfaction and hygiene [14]. Beyond these physical attributes, the study places significant emphasis on the biological performance of the nanogel, particularly its antimicrobial and anti-inflammatory activities. These pharmacodynamic parameters are central to the therapeutic efficacy of the formulation. The inclusion of potent herbal agents—known for their antibacterial, antiseptic, and soothing properties—aims to target acne at its root causes by inhibiting the growth of Cutibacterium acnes and reducing the inflammation associated with acne lesions [15]. Through this multifaceted evaluation, the final polyherbal nanogel formulation is envisioned as a promising alternative to conventional synthetic acne treatments. It is designed to offer superior skin tolerability, minimize potential side effects, and deliver sustained therapeutic benefits. By combining the strengths of traditional herbal medicine with modern nanotechnology, this research aims to contribute a clinically viable, consumer-friendly, and environmentally safe solution to the ongoing challenge of acne management [16]. The development of this polyherbal nanogel presents a transformative approach to acne treatment, particularly in the context of increasing antibiotic resistance and the side effects associated with conventional synthetic therapies. Unlike traditional formulations that rely heavily on antibiotics, this nanogel offers a resistance-free therapeutic solution, minimizing the risk of microbial adaptation and long-term inefficacy. Rooted in the principles of natural medicine, the formulation embodies a scientifically validated herbal therapy, combining multiple botanicals with proven anti-inflammatory and antimicrobial properties. Its composition ensures not only efficacy but also safety and skin compatibility, making it an ideal candidate for both chronic management and preventive care of acne [17]. Beyond its immediate dermatological applications, this nanogel formulation demonstrates significant promise for scalability and commercialization. Its foundation in natural, well-tolerated ingredients aligns with the growing global demand for herbal-based cosmetic and therapeutic products, positioning it favorably in the burgeoning cosmeceutical market. Importantly, in light of the rising concerns regarding synthetic agents, drug resistance, and adverse dermatological reactions, this research initiative serves as a meaningful step toward the integration of traditional Ayurvedic wisdom with the technological advancements of modern pharmaceutics. It highlights the potential of harmonizing time-tested herbal practices with contemporary drug delivery innovations, opening new avenues for safe, effective, and sustainable dermatological solutions [18].

MATERIALS AND METHODS

Ingredients

1. Orange Peel Extract

Table 1. Phytochemical profile and therapeutic attributes of Orange Peel Extract (Citrus × sinensis) used in polyherbal anti-acne nanogel formulation.

Orange peel extract, derived from the outer rind of Citrus × sinensis, belongs to the family Rutaceae and is a hybrid between Citrus maxima (pomelo) and Citrus reticulata (mandarin orange). The fruit is indigenous to Southeast Asia but is now cultivated globally due to its widespread applications in food, cosmetics, and medicine. Phytochemically, orange peel is rich in essential oils (notably limonene), flavonoids, polyphenols, sugars, and dietary fiber. These bioactive compounds contribute significantly to its antimicrobial, antioxidant, and anti-inflammatory properties—making it a viable therapeutic agent in dermatological applications, particularly for acne. The antibacterial activity of orange peel extract is primarily attributed to limonene and hesperidin, which disrupt bacterial membranes and inhibit the growth of acne-associated pathogens like Staphylococcus aureus and C. acnes. Additionally, the antioxidant profile of the peel helps neutralize reactive oxygen species (ROS), which play a role in inflammation and lesion formation in acne vulgaris [19]. From a dermal application standpoint, orange peel extract also contributes to sebostatic regulation, reducing excess oiliness—a key concern in acne-prone skin. Furthermore, its natural citrus acids support mild exfoliation, promoting skin renewal and preventing comedone formation. In the current study, 1 gram of orange peel extract was incorporated into the nanogel formulation, where it acted synergistically with other botanicals like turmeric and neem to provide a comprehensive anti-acne action. Its compatibility with other components and stability in the gel matrix make it an essential component of the polyherbal formulation [20].

Figure 1: Orange peel extract

2.Turmeric Extract

Table 2: Pharmacognostic and Therapeutic Profile of Turmeric (Curcuma longa) Extract Used in Polyherbal Anti-Acne Nanogel Formulation

Turmeric (Curcuma longa), a perennial herb belonging to the Zingiberaceae family, has been widely recognized for its extensive therapeutic value in traditional medicine systems such as Ayurveda, Unani, and Traditional Chinese Medicine. The rhizome of this plant, commonly known as turmeric, is a rich source of curcuminoids, with curcumin being the principal bioactive compound responsible for its characteristic yellow color and medicinal properties. Curcumin exhibits a broad spectrum of biological activities, including antimicrobial, anti-inflammatory, antioxidant, antineoplastic, and wound-healing effects. These properties render turmeric particularly effective in the management of acne vulgaris, an inflammatory skin condition that arises due to bacterial colonization (primarily by Cutibacterium acnes), excessive sebum secretion, and follicular hyperkeratinization. Through inhibition of the nuclear factor-kappa B (NF-κB) pathway and suppression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), curcumin helps attenuate the inflammatory response associated with acne lesions [21]. Additionally, turmeric demonstrates notable antibacterial activity against a wide range of skin pathogens, including Staphylococcus aureus and C. acnes, both of which are implicated in acne pathogenesis. The antioxidant action of curcumin further aids in neutralizing reactive oxygen species (ROS), which are known to contribute to tissue damage and post-acne pigmentation [22]. In the present study, turmeric extract has been incorporated into the polyherbal nanogel to exploit its multifaceted therapeutic profile. The inclusion of turmeric not only helps in the direct eradication of acne-causing microbes but also promotes soothing of inflamed skin, reduces erythema, and supports skin regeneration. When formulated into a nanogel delivery system, the bioavailability and skin penetration of curcumin are significantly enhanced, allowing for sustained release and improved therapeutic outcomes. Numerous studies have validated the dermatological benefits of turmeric in topical formulations. For instance, Sharma et al. (2020) and Sahoo et al. (2021) reported significant clinical improvement in acne symptoms using turmeric-based nanogels, reinforcing the evidence for its efficacy in cosmeceutical applications.Given its low toxicity profile, historical usage, and substantial scientific evidence, turmeric stands as a cornerstone component of the polyherbal anti-acne nanogel, contributing meaningfully to its anti-inflammatory and antimicrobial activity while maintaining skin integrity and health [23].

Figure 2: Turmeric extract

3. Neem Extract

Table 3: Pharmacognostic and Therapeutic Profile of Neem (Azadirachta indica) Extract Used in Polyherbal Anti-Acne Nanogel Formulation [24]

Neem (Azadirachta indica), a widely revered medicinal plant in traditional Ayurvedic systems, plays a pivotal role in the formulation of polyherbal anti-acne nanogel due to its extensive therapeutic properties. Belonging to the family Meliaceae, neem has been used for centuries in Indian medicine for managing a variety of skin ailments, particularly those involving microbial infections and inflammation. In the present formulation, neem extract is included as one of the core active ingredients owing to its broad-spectrum antimicrobial and anti-inflammatory capabilities. Its bioactive constituents, such as nimbin, nimbidin, azadirachtin, quercetin, and salannin, have been scientifically demonstrated to exhibit potent antibacterial activity, especially against Propionibacterium acnes and Staphylococcus aureus—the primary causative agents of acne vulgaris. These compounds disrupt microbial membranes and inhibit bacterial growth, thereby helping to reduce lesion formation and prevent further skin infection [25]. Beyond its antimicrobial role, neem also exhibits strong anti-inflammatory effects by suppressing pro-inflammatory cytokines and modulating immune responses. This helps in alleviating erythema, swelling, and discomfort associated with inflamed acne lesions. Moreover, neem possesses antioxidant properties that aid in neutralizing reactive oxygen species (ROS) and preventing oxidative damage to skin tissues, further contributing to acne control and skin healing. Incorporating neem extract into a nanogel delivery system significantly enhances its dermal absorption and stability. Nanogels facilitate better penetration of the active phytochemicals through the skin barrier, ensuring a sustained and targeted therapeutic effect. This approach not only amplifies the antibacterial efficacy of neem but also minimizes potential skin irritation often associated with concentrated herbal extracts. The neem extract serves as a critical component in the polyherbal anti-acne nanogel, offering a natural, multi-functional approach to acne management. Its inclusion in the formulation underscores the objective of delivering a holistic, herbal-based therapy that is both effective and safe for long-term use. By leveraging neem's pharmacological strengths within a nanogel matrix, the formulation advances beyond conventional acne treatments and moves toward a modern, biocompatible, and resistance-free dermatological solution [26].

Figure 3: Neem (Azadirachta indica) extract

4. Tea Tree Oil

Table 4: Tea Tree Oil – Botanical and Pharmacological Profile [27]

Tea tree oil, extracted from the leaves of Melaleuca alternifolia of the family Myrtaceae, is a well-recognized essential oil with potent antimicrobial and anti-inflammatory properties. Its inclusion in the polyherbal anti-acne nanogel is based on strong scientific evidence supporting its effectiveness in treating acne vulgaris, particularly due to its ability to target acne-causing bacteria such as Cutibacterium acnes and Staphylococcus aureus. The primary bioactive compound in tea tree oil is terpinen-4-ol, which has been demonstrated to disrupt bacterial membranes, leading to cell lysis and death. Additionally, terpinen-4-ol exhibits anti-inflammatory activity by suppressing the production of pro-inflammatory cytokines, thereby reducing swelling and redness associated with acne lesions. In the context of nanogel formulation, tea tree oil contributes multiple functional benefits. Firstly, it enhances the antimicrobial spectrum of the formulation, complementing the effects of other phytoconstituents such as curcumin (from turmeric) and azadirachtin (from neem). Secondly, due to its lipophilic nature, it aids in the penetration of active ingredients through the skin barrier, facilitating deeper delivery into sebaceous follicles—the primary site of acne pathology. Moreover, the use of nanotechnology ensures stabilization of volatile components like terpinen-4-ol and minimizes potential skin irritation that can occur with direct application of undiluted essential oils. In a nanogel matrix, tea tree oil is uniformly dispersed within the hydrophilic environment, allowing for controlled release and enhanced bioavailability, while maintaining skin compatibility. Studies such as those by Patel et al. (2021) and Choudhary et al. (2020) have demonstrated that tea tree oil-loaded nanogels significantly reduce acne lesions and improve skin texture, with minimal side effects [28]. These findings substantiate its role in modern dermal formulations as both a therapeutic and cosmetically acceptable ingredient. The tea tree oil serves as a critical component in the polyherbal nanogel formulation due to its broad-spectrum antibacterial efficacy, ability to reduce inflammation and sebum, and its compatibility with nanocarrier systems. Its inclusion ensures a holistic, well-tolerated, and efficacious approach to acne management within a natural, plant-based therapeutic framework [29].

Figure 4: Tea Tree Oil

5. Honey

Table 5: Botanical Profile of Honey [30]

Figure 5: Honey

Honey, derived from the nectar of flowers through the enzymatic activity of Apis mellifera (the honeybee), plays a vital role in the formulation and therapeutic profile of polyherbal anti-acne nanogels. As a natural ingredient, honey offers multiple pharmacological benefits, making it an essential component in dermatological preparations, especially those targeting inflammatory skin conditions such as acne vulgaris. In the context of nanogel formulation, honey serves as a moisturizing agent and humectant, helping to maintain optimal hydration of the skin. Its high content of sugars, proteins, enzymes, vitamins, and minerals contributes not only to moisture retention but also promotes tissue repair and wound healing. The antibacterial properties of honey are well-documented; it exerts bacteriostatic and bactericidal actions against acne-causing bacteria like Cutibacterium acnes and Staphylococcus epidermidis. This antimicrobial activity is primarily attributed to its low pH, hydrogen peroxide content, and high osmolarity [6]. Moreover, honey provides a soothing effect, reducing inflammation and skin irritation, which is particularly beneficial for individuals with sensitive or acne-prone skin. Its natural composition ensures compatibility with other herbal extracts such as turmeric, neem, and tea tree oil, enhancing the overall therapeutic effect of the nanogel while minimizing adverse effects [31]. In the preparation of the polyherbal nanogel, honey is incorporated into the aqueous phase along with guar gum to form a semi-solid gel matrix, contributing to the spreadability, texture, and stability of the final formulation. It complements the action of the other botanicals, reinforcing the gel’s anti-inflammatory, antimicrobial, and skin-nourishing properties. Thus, honey not only enriches the pharmacodynamic profile of the nanogel but also supports the product’s commercial appeal by aligning with the growing consumer demand for natural and safe skin care solutions [32].

6.Guar Gum

Table 6: Botanical Profile of Guar Gum (Cyamopsis tetragonoloba) [33]

Figure 6: Guar Gum

Guar gum plays a pivotal role in the formulation and stabilization of polyherbal anti-acne nanogels due to its exceptional gelling, thickening, and stabilizing properties. Derived from the endosperm of the seeds of Cyamopsis tetragonoloba, a leguminous plant belonging to the family Fabaceae, guar gum is a naturally occurring polysaccharide primarily composed of galactomannan. Its biocompatibility, non-toxicity, and biodegradability make it an ideal candidate for topical pharmaceutical and cosmeceutical applications. In the context of anti-acne nanogel preparation, guar gum serves as the primary gelling agent, providing the necessary viscosity and consistency to the formulation. It allows for the incorporation of hydrophilic and hydrophobic herbal extracts within a stable, aqueous gel matrix. Its high water-binding capacity contributes to enhanced hydration of the skin while forming a smooth, spreadable base that facilitates even distribution of active ingredients across the affected area. Moreover, guar gum supports controlled drug release, an essential attribute of nanogels. By forming a semi-solid gel network, it helps encapsulate the polyherbal actives—such as turmeric, neem, tea tree oil, orange peel extract, and honey—and modulates their diffusion through the skin [34]. This ensures prolonged contact time with the dermal layers, improving the therapeutic efficacy of the gel while minimizing the frequency of application. The gelling nature of guar gum also enhances the mechanical and aesthetic properties of the nanogel. It imparts a non-greasy, smooth texture that is gentle on acne-prone skin, reducing the risk of pore blockage or irritation. Its natural origin further aligns with the formulation's focus on herbal and non-synthetic components, making it suitable for sensitive skin types. In addition, guar gum demonstrates stability-enhancing characteristics, helping maintain the homogeneity and shelf life of the nanogel by preventing phase separation and settling of active ingredients. It aids in achieving a uniform consistency and pH, both of which are crucial for consumer acceptability and therapeutic performance. Overall, the incorporation of guar gum into the polyherbal anti-acne nanogel is instrumental in ensuring the structural integrity, usability, and functional efficiency of the formulation. It bridges traditional botanical efficacy with modern delivery systems, reinforcing the gel’s potential as a safe, natural, and effective solution for acne management [35].

7.Ethanol

Ethanol was employed in the formulation of the polyherbal anti-acne nanogel as a solvent and co-solvent due to its excellent solubilizing properties for both hydrophilic and lipophilic phytoconstituents. It facilitated the efficient extraction of active phytochemicals from the selected medicinal plants and aided in their uniform dispersion within the gel matrix. Moreover, ethanol served as a permeation enhancer, improving skin penetration of the encapsulated herbal actives. Its antimicrobial properties also contributed to the overall preservative effect, enhancing the microbiological stability of the formulation. The concentration of ethanol was optimized to balance solubility, stability, and dermal safety, ensuring the efficacy and tolerability of the nanogel for topical anti-acne therapy [36].

Figure 7: Ethanol

8. Glycerin

Glycerin, also known as glycerol, is a trihydroxy alcohol widely used in pharmaceutical and cosmetic formulations due to its excellent humectant, emollient, and moisturizing properties. In the present study, glycerin was incorporated as a key component in the preparation of the polyherbal anti-acne nanogel to enhance skin hydration, improve spreadability, and provide a soothing effect upon application. Its hygroscopic nature helps maintain skin moisture levels by attracting water from the environment, thereby preventing dryness and irritation commonly associated with acne treatments. Moreover, glycerin contributes to the stability and consistency of the gel matrix, ensuring uniform distribution of the herbal nanoactives. Its non-comedogenic and biocompatible profile makes it suitable for acne-prone and sensitive skin, further supporting the therapeutic goals of the formulated nanogel [37].

Figure 8: Glycerin

9. Lemon Juice

Table 7: Botanical Profile of Lemon Juice (Citrus limon) [38]

Figure 9: Lemon juice

Lemon juice, extracted from Citrus limon, was incorporated into the polyherbal anti-acne nanogel formulation for its well-documented therapeutic properties. Rich in vitamin C (ascorbic acid), citric acid, and various bioactive phytochemicals, lemon juice possesses potent antimicrobial, astringent, antioxidant, and keratolytic activities that are beneficial in the treatment of acne vulgaris. Its natural acidity helps in exfoliating dead skin cells, unclogging pores, and reducing sebum production, thereby minimizing acne formation. Furthermore, the antibacterial action of lemon juice against Propionibacterium acnes and Staphylococcus aureus supports its role as an effective herbal agent in acne management. In the nanogel system, lemon juice also contributes to the stability and synergistic activity of the formulation when combined with other herbal extracts. Its inclusion in the polyherbal nanogel enhances the therapeutic potential of the formulation through a multi-targeted approach, promoting clearer skin with minimal irritation [39].

METHOD OF PREPARATION [40]
The drug is dissolved in ethanol and propylene glycol with stirring (organic phase).

Dissolve gaur gum in water with stirring until a gel forms (aqueous phase)

the drug phase is added dropwise into the aqueous phase during high-speed homogenization to nanodroplets.

Lemon juice is added with continuous stirring to adjust pH and form nanogel

Filled in a suitable container, and labelled

Composition of Various Polyherbal Nanogel Formulations

Table 8: Composition of Polyherbal Anti-Acne Nanoge [41]

Evaluation of Polyherbal Nanogel [42]

Physical evaluation

Physical parameters such as colour, appearance, and consistency were checked in the prepared formulations.

Colour: The colour of the formulation was checked out visually against a white background.

Consistency: The consistency was checked by applying it to the skin.

Greasiness: The greasiness was assessed by the application on the skin.

Odour: The odour of the nanogel was checked by mixing the nanogel in water and taking the smell.

Washability

• • Formulations were applied to the skin, and then the ease and extent of washing with water were checked manually.

Determination of pH

• • The pH of formulations was determined using a digital pH meter.

Spreadability

• • The spread ability of the formulation was found manually by applying the gel on the surface and spread.

RESULT AND DISCUSSION

The polyherbal nanogel (50g) was formulated as per the prescribed procedure and evaluated for various physical parameters. The different nanogel formulations were prepared using varying amounts of Guar gum. Other ingredients used are Guar gum as gelling agent, lemon juice as neutraliser, propylene glycol as humectants and ethanol as an anti-microbial agent. Finally, the volume of formulations was adjusted with distilled water. The formulation was also evaluated for various quality parameters, and result revealed that the formulation possessed all desired quality parameters as mentioned below.

Table 9: Observation and Evaluation of anti-acne nanogel