Design and In-Vitro Evaluation of Kaempferol-Loaded Emulgel as a Novel Topical Anti-Inflammatory Drug Delivery System

Abstract

Background: Inflammation is a complex biological response associated with various pathological conditions, necessitating the development of effective and safer therapeutic strategies. Kaempferol, is a naturally occurring flavonoid that exhibits significant anti-inflammatory, antiproliferative, and antioxidant properties but limited due to low bioavailability.

Methods: The emulgel was formulated using Carbopol 934 as a gelling agent and a combination of Span 20 and Tween 80 as surfactants to stabilize an oil-in-water emulsion system. Emulgel was assessed for physicochemical properties, drug release, drug content, and stability over 90 days following anti-inflammatory activity.

Results: The developed emulgel exhibited desirable characteristics, including smooth texture, homogeneous appearance, non-greasy, and good washability. The pH (6.40 ± 0.01) was within acceptable skin-compatible range, while viscosity and spreadability values indicated suitable rheological behavior. Drug release studies proved controlled release with 91.73% cumulative drug release over 24 hours. The drug content was found to be 98.93 ± 0.29%. The formulation demonstrated notable biological activities. Stability studies indicated minimal changes in physicochemical parameters under both room temperature and accelerated conditions.

Conclusion: The developed kaempferol emulgel exhibited potential as a topical anti-inflammatory delivery system for localized inflammatory conditions.

Introduction

Inflammation is the protective response to harmful stimuli to preserve tissue balance and trigger repair mechanisms (1-3). Although acute inflammation is protective, prolonged or uncontrolled inflammatory responses lead to various pathological conditions, including dermatitis, arthritis, and other chronic inflammatory disorders (4-6).

Though effective, long-term use of anti-inflammatory conventional therapies exhibit adverse effects, including gastrointestinal irritation, renal complications, and cardiovascular risks (7-9). These limitations prompted the search for safer and more targeted therapeutic alternatives, chiefly those derived from natural sources. Historically, herbal medicines have been a good source of compounds for modern drug discovery. Still today, underdeveloped countries depend on ethnobotanicals for healthcare (10). These plants are rich in phytochemicals and exhibit significant pharmacological potential, among which flavonoids have attracted considerable attention for their anti-inflammatory, antioxidant, antimicrobial, and cytoprotective effects (11-13).

Kaempferol is naturally occurring flavone in fruits, vegetables, and medicinal plants and emerged as a promising therapeutic candidate in many studies (14-16). Although, it exhibits broad pharmacological effects (17-19) its use is limited due to compromised bioavailability, restricting effective delivery through conventional formulation (20-22). Thus, topical drug delivery systems offer an effective approach to treat localized inflammatory conditions. Topical formulations reduce systemic exposure, enhance patient compliance, and deliver drug directly to the site of inflammation. Nonetheless, conventional topical vehicles often face challenges in delivering poorly water-soluble drugs due to inadequate release and limited skin penetration (23-25).

Interestingly, emulgel can address above limitation to enhance skin penetration with controlled drug release (26-28). But, choice of components is critical for optimal performance. Carbopol-based gels are widely employed due to biocompatibility, rheological properties, and controlled release. Next, dual surfactant system (Span 20 + Tween 80) improves stability and drug distribution in formulation (29-31). Based on this, we developed and evaluated emulgel by using kaempferol (Figure 1). The objective was to enhance kaempferol solubility, stability, and local bioavailability through emulsion-in-gel system. Study also evaluates physicochemical properties, drug release, and anti-inflammatory related biological activities activity to support the potential of this formulation as an effective topical strategy for localized inflammatory conditions.

2.1. Preliminary Qualitative Analysis of Flavonoid Functional Groups in Kaempferol

Kaempferol was obtained gift from Chemical Book, China. All ingredients, including Carbopol 934, propylene glycol, ethanol, triethanolamine (TEA), Span 20, and Tween 80, were procured from SD Fine Chemicals (Gujarat, India).
Preliminary qualitative tests were performed to confirm sample as flavonoid. In the Shinoda test (32, 33), 1 mL of sample dissolved in alcohol was treated with several magnesium turnings and few drops of concentrated hydrochloric acid, producing faint pinkish-red color, indicative of flavonoids. Similarly, alkaline reagent test further confirmed their presence, as sample solution turned yellow upon treatment with sodium hydroxide and reverted to colorless with the addition of a few drops of diluted acid (34, 35). These results collectively validate the presence of flavonoid groups in the kaempferol sample.

2.2. Formulation of kaempferol emulgel

The preparation began with gel base using Carbopol 934, which was dispersed in purified water with continuous gentle stirring and allowed sufficient time to swell completely, ensuring the development of uniform and viscous matrix. Gradual incorporation of triethanolamine neutralized the dispersion and resulted in the formation of a clear, uniformly structured gel suitable for topical application (36-38). An o/w emulsion was prepared by dissolving kaempferol and preservatives in a mixture of propylene glycol and ethanol, providing an appropriate solvent system for poorly water-soluble drug (39-41). Sesame oil and Span 20 were then added to form oil phase, which was thoroughly mixed to achieve uniform distribution (42-44). Purified water was gradually added under vigorous stirring to complete emulsion, and Tween 80 was used as stabilizing surfactant to maintain integrity and prevent phase separation during storage. Finally, prepared emulsion was incorporated into gel base at room temperature under continuous stirring until uniform and consistent emulgel was formed. The final weight of formulation was adjusted using purified water, and gentle stirring was applied to ensure complete homogeneity throughout the product. This stepwise process resulted stable, well-structured kaempferol emulgel suitable for effective topical delivery. The composition of kaempferol-loaded emulgel and specific functions of ingredients are summarized (Table 1).

Table 1: Ingredients composition in the formulation of emulgel

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Siddhi A. Vernekar, Vaishnavi G. Keluskar, Anant S. Kerkar, Sainath S. Kharat, Isha V. Kudalkar, Prerana P. Kulkarni, Design and In-Vitro Evaluation of Kaempferol-Loaded Emulgel as a Novel Topical Anti-Inflammatory Drug Delivery System, Journal of Integrative and Translational Biomedicine, Volume 1, Issue 2 (May-August 2026) | Page No: 65-76 | e-ISSN: Applied

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