Composition of a nanostructured lipid carrier system for the effective treatment of arthritis

Abstract

Composition of a nanostructured lipid carrier system for the effective treatment of arthritis, the composition comprising: (a) Daidzein as a pharmaceutically active ingredient; (b) a solid lipid selected from glyceryl monostearate, stearic acid, cetyl palmitate or combinations thereof; (c) a liquid lipid selected from oleic acid, caprylic / capric triglyceride, medium-chain triglycerides or mixtures thereof; (d) one or more surfactants selected from Tween 80, Poloxamer 188, Span 20 or combinations thereof; (e) one or more co-surfactants selected from propylene glycol, polyethylene glycol, ethanol or combinations thereof; (f) an aqueous phase suitable for the formation of a stable nanodispersion; wherein the nanostructured lipid carrier has a particle size between 50 and 300 nm, a polydispersity index ≤ 0.5 and an inclusion efficiency of at least 70% and wherein the composition is formulated to provide improved skin permeation and delayed release of daidzein for an anti-inflammatory and anti-arthritic effect.

Description

[0001] The present invention relates to a pharmaceutical composition comprising nanostructured lipid carriers (NLCs) designed for the effective treatment of arthritis. It relates in particular to the development of a lipid-based nanoformulation that improves the solubility, stability, and targeted delivery of the active ingredient to inflamed joint tissue. The invention further relates to its application for improving anti-inflammatory efficacy and delayed release in arthritis therapy.

[0002] Arthritis remains one of the most prevalent chronic inflammatory diseases, significantly impacting mobility and quality of life. Conventional therapies, including oral NSAIDs and corticosteroids, often provide only temporary relief and are associated with serious gastrointestinal, renal, and cardiovascular side effects when used long-term. Many arthritis medications also suffer from poor solubility, limited bioavailability, and inadequate penetration into inflamed joint tissue, reducing their therapeutic efficacy and necessitating frequent dosing. Therefore, there is a significant need for safer, localized, and more efficient drug delivery systems that can overcome these limitations.

[0003] Topical formulations have emerged as a promising alternative for the treatment of arthritis; however, their efficacy is largely limited by the stratum corneum barrier and the restricted diffusion of active ingredients. Natural bioactive compounds such as daidzein have demonstrated anti-inflammatory and anti-arthritic potential, but their therapeutic use is limited by poor solubility, instability, and low skin permeability. Conventional gels or creams do not guarantee deep skin penetration, sustained release, or high drug retention at the target site, resulting in suboptimal clinical outcomes.

[0004] To address these challenges, nanostructured lipid carriers (NLCs) offer a novel and technologically advanced solution for drug delivery. Their unique combination of solid and liquid lipids creates an imperfect crystal structure that enhances drug loading, increases stability, and enables sustained release. NLCs can efficiently bypass skin barriers, increase skin retention, and ensure controlled delivery of poorly soluble drugs such as daidzein. Therefore, the development of a daidzein-loaded NLC formulation offers a strategic, problem-solving approach for the safe, effective, and targeted treatment of arthritis with minimized systemic side effects.

[0005] One objective of the present disclosure is to provide a pharmaceutical composition based on a nanostructured lipid carrier (NLC) that improves the delivery of antiarthritic drugs through the skin.

[0006] Another objective of the present disclosure is to improve the solubility and stability of daidzein by incorporating it into a lipid-based nanotransport system.

[0007] Another objective of the present disclosure is to achieve a higher drug loading and improved encapsulation efficiency through the use of a mixed solid-liquid lipid matrix.

[0008] Another objective of the present disclosure is to develop a composition that enables a sustained and controlled release of the active ingredient for a prolonged therapeutic effect.

[0009] Another objective of the present disclosure is to improve skin penetration and retention of the active ingredient in inflamed arthritic areas.

[0010] Another objective of the present disclosure is to reduce the systemic side effects often associated with oral antiarthritic drugs by means of localized drug delivery.

[0011] Another objective of this disclosure is to use biocompatible lipids and surfactants that ensure the safety, stability and acceptance of the formulation for the patient.

[0012] Another objective of the present disclosure is to provide a formulation that has improved rheological properties suitable for topical application.

[0013] Another objective of the present disclosure is to enable a more efficient therapeutic response through improved bioavailability and targeted delivery to the affected tissue.

[0014] Another objective of the present disclosure is to offer a technologically advanced and patient-friendly alternative to conventional arthritic formulations.

[0015] The present invention relates generally to a composition based on a nanostructured lipid carrier (NLC) designed for the effective delivery of antiarthritic agents. The invention provides a lipid matrix that combines solid and liquid lipids to improve stability and loading efficiency. The composition is suitable for topical application to enhance the local therapeutic effect.

[0016] One embodiment of the present invention comprises daidzein being incorporated into an NLC system to overcome its poor solubility and limited permeability. This embodiment ensures improved encapsulation within the lipid matrix. It further enables a controlled and sustained release of the active ingredient.

[0017] Another embodiment of the invention relates to a method for producing the NLC composition using melt emulsification and ultrasonic treatment. This method ensures a uniform particle size and improved distribution of the drug within the lipid matrix. It supports the scalable and reproducible development of formulations.

[0018] Another embodiment of the invention is a topical gel containing the optimized NLC formulation dispersed in a suitable gel base. The gel offers improved spreadability, skin compatibility, and ease of application for the patient. It enables effective penetration and retention of the drug at the inflamed site.

[0019] Another embodiment of the invention involves the use of biocompatible surfactants and lipids that maintain the structural integrity of the nanocarrier. This enables improved stability, minimized aggregation, and enhanced therapeutic performance. The composition remains suitable for long-term storage and clinical use.

[0020] Another embodiment of the invention aims to improve the local delivery of the active ingredient to arthritic joints while simultaneously minimizing systemic exposure. This enables a targeted anti-inflammatory effect with reduced side effects. The invention represents a technologically advanced alternative to conventional formulations.

[0021] The present invention relates to a novel drug delivery system comprising diazepam-loaded nanostructured lipid carriers (DZ-NLCs) embedded in a topical gel formulation designed for enhanced transdermal delivery. The invention strategically combines solid and liquid lipids with optimized surfactants to create stable NLCs that efficiently encapsulate diazepam while simultaneously improving its permeation through the skin barrier. The gel matrix further enhances the system by enabling delayed release, improved drug retention at the application site, and excellent patient compliance.This technologically advanced formulation aims to overcome the limitations of conventional diazepam administration—such as poor water solubility, limited permeability, variable bioavailability, and systemic side effects—by providing a controlled, localized, and effective transdermal therapeutic platform. The invention offers an innovative approach to neurological and muscle-relaxing therapy where sustained, non-invasive drug delivery is required.

[0022] A nanostructured lipid carrier composition for the effective treatment of arthritis, comprising daidzein as a pharmaceutical active ingredient, a solid lipid selected from glyceryl monostearate, stearic acid, cetyl palmitate or combinations thereof, a liquid lipid selected from oleic acid, caprylic / capric triglyceride, medium-chain triglycerides or mixtures thereof, one or more surfactants selected from Tween 80, Poloxamer 188, Span 20 or combinations thereof, one or more co-surfactants selected from propylene glycol, polyethylene glycol, ethanol or combinations thereof, and an aqueous phase suitable for the formation of a stable nanodispersion, wherein the nanostructured lipid carrier has a particle size in the range of 50 to 300 nm, a polydispersity index of 0.5 or less, an inclusion efficiency of at least 70%, and a zeta potential in the range of -20 mV to -40 mVand wherein the composition is formulated to provide improved skin permeation and delayed release of daidzein for anti-inflammatory and anti-arthritic action, wherein the solid lipid is optionally glyceryl monostearate in an amount of 2% to 10% (w / w), wherein the liquid lipid is optionally oleic acid in an amount of 1% to 6% w / w, the surfactant optionally comprises Tween 80 in an amount of 1% to 5% w / w, and the daidzein loading capacity is in the range of 40% to 60% w / w relative to the lipid matrix. Example 1: Production of nanolipid carriers (NLCs)

[0023] Nanolipid carriers (NLCs) were fabricated using a hot emulsification ultrasonic process that combines thermal melting and high-energy dispersion techniques. Daidzein (DZ) was dispersed in a molten lipid mixture of glyceryl monostearate (GMS, 70%) and tocopherol (30%), and the mixture was heated for 5 minutes. An aqueous phase of water and poloxamer 188 was prepared separately, and the hot lipid phase was slowly added to the aqueous medium with continuous stirring to form a primary emulsion. The volume was made up to 100 ml, and the emulsion was allowed to cool before being subjected to ultrasonic treatment for 20 minutes to reduce the droplet size. The resulting NLC dispersion was immediately cooled in an ice bath to solidify the nanoparticles, which were then stored for further characterization. Example 2: Experimental design

[0024] To optimize the formulation, a Box-Behnken design (BBD) was used with Design-Expert software version 13. Three independent variables—total lipid concentration (X1), surfactant concentration (X2), and ultrasound treatment duration (X3)—were investigated at three levels (-1, 0, +1) selected based on preliminary experiments. The goal was to develop optimized daidzein-loaded NLCs (DZ-NLCs) by evaluating their influence on two dependent reactions: particle size (Y1) and encapsulation efficiency (Y2). Statistical modeling and analysis were performed to determine the optimal formulation that yielded minimum particle size with maximum encapsulation efficiency.

[0025] The development process began with the selection of suitable lipids. Various solid lipids were investigated, and cetyl palmitate was identified as the most suitable solid lipid for the formulation. Tocopherol was selected as the liquid lipid due to its ability to dissolve the maximum amount of the active ingredient, while poloxamer 188 was chosen as the surfactant to stabilize the nanostructured system. Nanostructured lipid carriers (NLCs) were fabricated using melt emulsification followed by ultrasonic treatment, and optimization was performed using a Box-Behnken design. In this design, the lipid content (X1), surfactant concentration (X2), and ultrasonic treatment time (X3) were considered independent variables, while particle size (Y1) and encapsulation efficiency (Y2) served as dependent responses.The response surface analysis was performed using three-dimensional model graphics derived from a quadratic polynomial model, which allowed the influence of the independent factors on the formulation properties to be visualized.

[0026] The optimization results showed that the improved NLC formulation exhibited only minimal deviations between predicted and experimental values, resulting in a small percentage deviation for both particle size and encapsulation efficiency. The optimized formulation demonstrated the best balance between small particle size and high encapsulation rate, thus proving superior to other batches. Based on these properties, the formulation designated NLCs-4 was identified as the optimal one among the various batches produced, as it exhibited a desirable nanometer size and improved drug loading suitable for effective therapeutic application. Example 3: Evaluation of optimized NLCs

[0027] Optimized NLC formulations were evaluated using several analytical techniques. Particle size, polydispersity index (PDI), and zeta potential were measured using a Malvern Zeta Sizer based on dynamic light scattering principles.

[0028] The surface morphology was investigated using transmission electron microscopy, whereby the NLCs were diluted, stained with 2% phosphotungstic acid and applied to carbon-coated copper grids.

[0029] The results confirmed that the nanostructured lipid carriers exhibited a uniform and well-defined spherical morphology. Under various magnifications, the particles appeared smooth and discrete, suggesting a stable nanoscale architecture suitable for dermal application and efficient drug diffusion.

[0030] The compatibility of the active ingredient and excipient was determined using FT-IR spectroscopy between 4000 and 400 cm⁻¹. -1 investigated to determine possible interactions.

[0031] The results of the FTIR analysis showed that all important absorption peaks of daidzein and glyceryl monostearate remained clearly identifiable in their physical mixture, confirming the absence of chemical interactions between the drug and the lipid. The strong characteristic peaks of daidzein were also retained in the nanostructured lipid carriers, indicating that the drug was successfully incorporated into the lipid matrix without undergoing chemical changes and suggesting excellent drug-lipid compatibility.

[0032] The thermal behavior and stability were analyzed using differential scanning calorimetry over a temperature range of 25-200 °C under nitrogen purging.

[0033] The DSC results showed a sharp endothermic melting peak for daidzein at approximately 338–339 °C, while glyceryl monostearate exhibited a melting transition at approximately 60–65 °C. In contrast, the optimized nanostructured lipid carriers did not show the sharp melting peak of the pure drug, suggesting that daidzein was converted to an amorphous or molecularly dispersed form within the lipid matrix. This conversion is favorable for improved dissolution and controlled release, and the reduced thermal signal supports the formation of NLC-specific structural imperfections that enhance drug encapsulation.

[0034] XRD analysis revealed intense and sharp crystalline peaks for pure daidzein, confirming its crystalline nature, while glyceryl monostearate retained its characteristic peaks in the 18–22° range. However, the crystalline peaks of daidzein were absent in the optimized nanostructured lipid carriers, indicating a complete loss of crystallinity. The NLCs showed a diffractogram similar to that of glyceryl monostearate, meaning that daidzein was successfully converted into an amorphous or molecularly dispersed state, which is advantageous for improving the bioavailability of poorly soluble drugs.

[0035] The inclusion efficiency was calculated using the standard formula: EE (%) = (Wt - Ws) / Wt × 100, where Wt is the total amount of drug and Ws is the amount of drug not included.

[0036] The particle size of the optimized formulation was approximately 113.6 nm, with a narrow polydispersity index of 0.34, reflecting a uniform size distribution. The particle properties were influenced by the ratio of solid to liquid lipids, with a higher solid lipid content resulting in larger particle sizes. The achieved nanosize range is suitable for improved transdermal penetration. The zeta potential of the formulation showed a stable surface charge, confirming the good physical stability of the dispersion system. Example 4: Preparation of a daidzein-loaded NLC gel

[0037] Daidzein-loaded NLCs were incorporated into a topical gel using Carbopol 940 as the gel-forming polymer. Concentrations ranging from 0.5% to 1% were evaluated, and 0.7% Carbopol was selected to achieve optimal viscosity and a smooth texture. The NLC dispersion was gradually added to the hydrated Carbopol gel under mechanical stirring at 800 rpm until a uniform distribution was achieved. Triethanolamine (0.2 ml) was added to neutralize the Carbopol and form a stable gel matrix, while methylparaben was included as a preservative. The formulated gel exhibited good spreadability, appearance, and consistency suitable for topical application. Example 5: Evaluation of an NLC-based gel

[0038] The DZ-NLC gel underwent physicochemical and functional evaluation, including appearance, viscosity, pH, and spreadability. Viscosity was measured using a Brookfield viscometer, and pH was determined using a calibrated pH meter. In vitro drug release was investigated using a diffusion cell array with a semipermeable membrane (0.45 µm), phosphate buffer with a pH of 6.8 as the medium, and quantification at 255 nm. Release kinetics were analyzed using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models, and the best-fitting model was selected based on the correlation coefficients (R). 2). Ex vivo permeation studies were conducted using rat skin mounted on a Franz diffusion cell, comparing DZ-NLC gel and normal DZ gel over 8 hours and analyzing the samples spectrophotometrically.

[0039] The results show that the formulated NLC-based gel had a smooth texture and uniform appearance, with a skin-friendly pH of approximately 6.1 ± 0.2, indicating low irritant potential. The viscosity at room temperature was approximately 2356 ± 42 cP, reflecting an ideal semi-solid consistency for topical application. Spreadability was satisfactory, as the gel spread evenly under minimal shear force, thus facilitating easy application.

[0040] The in vitro diffusion study showed that the DZ-NLC formulation exhibited a biphasic release pattern. An initial rapid release of 25.29% occurred within the first two hours, attributed to daidzein being loosely bound to the surface of the lipid particles. This was followed by a further release of 36.8% over the next four hours and an additional release of 25.3% from the DZ gel over the following twelve hours, indicating sustained diffusion from the lipid matrix. The optimized formulation achieved a maximum cumulative release of 85.65% over 24 hours, whereas the commercially available gel showed a release of only 70% over the same period, confirming the uniform distribution and effective encapsulation of the drug within the NLC structure. Drug release kinetics were evaluated using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models.The respective correlation values ​​(R. 2 The values ​​were 0.555 for the zeroth order, 0.3859 for the first order, 0.8803 for the Higuchi model, and 0.8021 for the Korsmeyer-Peppas model. The Higuchi diagram showed the highest R 2 The value indicated that drug release was predominantly controlled by diffusion. Furthermore, the Korsmeyer-Peppas slope of 1.128 suggested supercase II transport, confirming that both diffusion and relaxation mechanisms contributed to the delayed release behavior of the DZ-NLC formulation.

[0041] Mathematical modeling of the release profile showed that the Higuchi model provided the best match, indicating diffusion-controlled release of daidzein from the nanostructured lipid carriers. The release exponent values ​​suggested that the mechanism was dominated by Fickian diffusion, confirming that the drug molecules were primarily released from the lipid matrix via a diffusion-based pathway. Example 6: In-vivo study

[0042] In vivo anti-arthritis activity was evaluated using Wistar rats (150-200 g) kept under controlled temperature (25 ± 2 °C), humidity (60-70 %) and a 12-hour light-dark cycle.

[0043] Rheumatoid arthritis was induced using Complete Freund's Adjuvant (CFA) according to established protocols. Animals were divided into five groups: normal, CFA control, standard (diclofenac 2% topical), DZ gel, and DZ-NLC gel. Paw volume and ankle diameter were measured with digital calipers on days 0, 7, 14, 21, and 28 to determine the percentage reduction in inflammation. Biochemical markers—including catalase, SOD, GSH, and lipid peroxidation—were assessed using tissue homogenates, while inflammatory markers (TNF-α, IL-6, IL-1β, IL-10) were quantified using ELISA kits. Radiographic imaging of the hind paws was performed using a Siemens Klinoskop-H X-ray unit to confirm post-treatment structural improvement.

[0044] Ex vivo permeation evaluation showed that the gel based on nanostructured lipid carriers exhibited significantly higher drug permeation through the skin compared to the conventional gel. This improved permeation can be attributed to the nanoscale particle size, the lipid composition, and the enhanced diffusivity, resulting in a considerably higher percentage of the active ingredient permeating over 24 hours.

[0045] The ex vivo permeation study showed that the daidzein-loaded NLC gel exhibited a significantly higher cumulative drug release compared to the conventional DZ gel. After 24 hours, the conventional DZ gel showed a permeation of 45.65% through rat skin, while the DZ-NLC gel showed a permeation of 75.4%. The commercially available gel formulation released 72% of the drug under the same conditions. These results suggest improved skin permeation and transdermal delivery of daidzein when incorporated into the NLC-based gel system. In vivo study on the treatment of arthritis - paw edema

[0046] Administration of Complete Freund's Adjuvant resulted in a significant increase in paw volume in the control group. Treatment with diclofenac, DZ-Gel, and DZ-NLCs-Gel led to a significant reduction in paw edema throughout the study. On day 28, the percentage reduction in paw volume was reported as 10.36 ± 1.95%, 93.16 ± 5.26%, 70.29 ± 5.37%, and 86.49 ± 5.62% for the control group, diclofenac group, DZ-Gel group, and DZ-NLCs-Gel group, respectively. Diclofenac showed the greatest reduction, while DZ-NLCs-Gel demonstrated superior anti-inflammatory activity compared to conventional DZ-Gel. Effect on catalase (CAT)

[0047] The catalase level in the CFA control group was significantly reduced to 0.38 ± 0.04 ± 0.04 ± 0.03 ± 0.03 ± 0.03 ± 0.03 ± 0.04 ± 0.04 ± 0.04 ± 0.04 ± 0.03 ± 0.04 ± 0.04 ± 0.05 ± 0.05 ± 0.05 ± 0.05 ± 0.05 ± 0.05 ± 0.05 ± 0.05 ± 0.04 ± 0.04 ± 0.04 ± 0.06 ± 0.04 ... Effect on superoxide dismutase (SOD)

[0048] CFA administration led to a substantial increase in SOD levels in the control group, measured at 189.51 ± 19.40 µg / mg tissue, compared to the normal group value of 8.72 ± 1.40 µg / mg tissue. Treatment reduced these elevated levels. Diclofenac significantly lowered SOD to 43.45 ± 6.80 µg / mg tissue. DZ-Gel and DZ-NLCs-Gel resulted in reductions to 118.21 ± 13.60 µg / mg tissue and 78.43 ± 9.97 µg / mg tissue, respectively, demonstrating a reduction in oxidative stress. Effect on reduced glutathione (GSH)

[0049] CFA-induced oxidative stress led to a decrease in GSH levels in the control group. Treatment with diclofenac, DZ-Gel, and DZ-NLCs-Gel significantly improved GSH concentrations. Diclofenac resulted in the greatest improvement, statistically superior to the DZ-NLCs-Gel group. Both DZ-Gel and DZ-NLCs-Gel showed an increase in GSH levels compared to the control group, but the difference between the two daidzein-treated groups was not statistically significant. Effect on lipid peroxidation (LPO)

[0050] The LPO value in the control group increased to 26.61 ± 3.11 nM / mg protein, compared to 8.41 ± 2.30 nM / mg protein in the normal group, indicating increased oxidative damage. Diclofenac significantly reduced LPO to 13.81 ± 2.60 nM / mg protein. DZ-NLCs gel also significantly reduced LPO to 16.32 ± 1.90 nM / mg protein. DZ gel further reduced LPO to 19.18 ± 2.10 nM / mg protein, but this reduction was not statistically significant compared to the control group. Analysis of inflammatory markers (TNF-α, IL-1β, IL-6, IL-10)

[0051] Administration of CFA led to increased levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokine IL-10 was reduced. Treatment with diclofenac, DZ-Gel, and DZ-NLCs-Gel significantly modulated these cytokines.

[0052] The DZ-NLCs gel group showed a significantly greater reduction in TNF-α, IL-1β, and IL-6 compared to the conventional DZ gel. Furthermore, the DZ-NLCs gel improved IL-10 levels more effectively, suggesting enhanced immunomodulatory and anti-inflammatory potential. Example 7: Statistical Analysis

[0053] All experiments were performed in triplicate, and data are presented as mean ± standard deviation (SD). Statistical significance was determined using analysis of variance (ANOVA), with p < 0.05 considered significant. This ensured the reliability and validity of the observed differences between the formulations and treatment groups. Example 8: Stability study

[0054] The stability test of the optimized DZ-NLC gel was performed for one month under controlled conditions (30 ± 2 °C and 65 ± 5% relative humidity) in a sealed glass container. Post-storage analysis included evaluation of the drug content, pH, viscosity, and in vitro drug diffusion to confirm that the formulation retained its physicochemical properties and therapeutic efficacy. The results confirmed the stability and robustness of the developed NLC-based topical gel.

[0055] The results show that the optimized DZ-containing NLC formulation exhibited excellent stability over a six-month period at 25 °C. The particle size remained nearly constant, decreasing only slightly from 113.6 nm to 112 nm. The inclusion efficiency gradually decreased from 79.2% to 76.2%, but remained within acceptable limits for NLC systems. No phase separation or precipitation was observed during the entire 180-day period, indicating good physical and structural stability of the formulation. Examples

[0056] 1. Composition of a nanostructured lipid carrier system for the effective treatment of arthritis, the composition comprising: (a) Daidzein as a pharmaceutically active ingredient; (b) a solid lipid selected from glyceryl monostearate, stearic acid, cetyl palmitate or combinations thereof; (c) a liquid lipid selected from oleic acid, caprylic / capric triglyceride, medium-chain triglycerides or mixtures thereof; (d) one or more surfactants selected from Tween 80, Poloxamer 188, Span 20 or combinations thereof; (e) one or more co-surfactants selected from propylene glycol, polyethylene glycol, ethanol or combinations thereof; (f) an aqueous phase suitable for the formation of a stable nanodispersion; wherein the nanostructured lipid carrier has a particle size between 50 and 300 nm, a polydispersity index ≤ 0.5 and an inclusion efficiency of at least 70% and wherein the composition is formulated to provide improved skin permeation and delayed release of daidzein for an anti-inflammatory and anti-arthritic effect.

Claims

[1] Composition of a nanostructured lipid carrier system for the effective treatment of arthritis, the composition comprising: (a) Daidzein as a pharmaceutically active ingredient; (b) a solid lipid selected from glyceryl monostearate, stearic acid, cetyl palmitate or combinations thereof; (c) a liquid lipid selected from oleic acid, caprylic / capric triglyceride, medium-chain triglycerides or mixtures thereof; (d) one or more surfactants selected from Tween 80, Poloxamer 188, Span 20 or combinations thereof; (e) one or more co-surfactants selected from propylene glycol, polyethylene glycol, ethanol or combinations thereof; (f) an aqueous phase suitable for the formation of a stable nanodispersion; wherein the nanostructured lipid carrier has a particle size between 50 and 300 nm, a polydispersity index ≤ 0.5 and an inclusion efficiency of at least 70% and wherein the composition is formulated to provide improved skin permeation and delayed release of daidzein for an anti-inflammatory and anti-arthritic effect. [2] Composition according to claim 1, wherein the solid lipid is glyceryl monostearate in an amount of 2 to 10 wt.% of the total formulation. [3] Composition according to claim 1, wherein the liquid lipid is oleic acid in a concentration of 1 to 6 wt.%. [4] Composition according to claim 1, wherein the surfactant Tween 80 comprises 1 to 5 wt.% of the composition. [5] Composition according to claim 1, wherein the nanostructured lipid carriers have a zeta potential in the range of -20 mV to -40 mV for improved physical stability. [6] Composition according to claim 1, wherein the daidzein loading capacity is in the range of 40% to 60% wt / wt based on the lipid matrix. [7] Composition according to claim 1, wherein the NLC-based daidzein formulation is incorporated into a topical gel base comprising carbopol, triethanolamine, glycerin and purified water. [8] Composition according to claim 1, wherein the composition provides a two-phase drug release comprising an initial rapid release followed by a sustained diffusion-controlled release for up to 24 hours. [9] Composition according to claim 1, wherein the formulation improves skin permeation by at least 30% compared to conventional daidzein gel formulations.