Daidzein liposome sunscreen composition for improved sun protection

Abstract

A topical sunscreen composition consisting of daidzein-loaded liposomes embedded in a cosmetically acceptable sunscreen base, wherein the liposomes have a mean vesicle size of approximately 198 nm and a polydispersity index of approximately 0.17 and are configured to increase the in vitro sun protection factor (SPF) and skin deposition of daidzein compared to a non-liposomal formulation.

Description

Field of invention

[0001] The invention relates to dermal application systems and photoprotective formulations, in particular a topical system in the form of a composition that uses daidzein-loaded liposomes. These were developed using QbD (Quality by Design) to increase the sun protection factor (SPF), skin deposition, and photostability in sunscreens. Background of the invention

[0002] Ultraviolet radiation induces oxidative stress, inflammation, and DNA damage, thus promoting photoaging and the development of skin cancer. Natural polyphenols mitigate these processes, but in conventional creams, they often exhibit poor skin penetration and instability. Liposomal encapsulation allows for the localization of UV filters and antioxidants within vesicles, thereby improving their residence time in the skin, reducing systemic permeation, and modulating their release. However, efficacy depends critically on vesicle size, polydispersity, charge, and membrane composition. Quality-by-design (QbD) approaches have become essential for liposome development. They link critical material properties and process parameters with key quality attributes such as vesicle size distribution and encapsulation efficiency to ensure robust and reproducible performance.Daidzein, a structurally related isoflavone to genistein, has proven dermatological benefits, including the stimulation of collagen synthesis via TGF-β / Smad signaling, which supports its potential to combat photoaging. However, its topical bioavailability and photoprotective effect as a monotherapy are limited without a suitable carrier. There remains a need for a sunscreen system that combines the biological photoprotective effect of daidzein with a QbD-optimized liposome architecture to achieve a higher sun protection factor (SPF), stronger skin deposition, and improved uniformity. This would result in superior protection against UV-induced skin damage. Summary of the invention

[0003] The invention relates to a daidzein-loaded liposomal sunscreen system consisting of phospholipid / cholesterol vesicles with a mean vesicle size of approximately 198 nm and a low polydispersity index close to 0.17 to ensure uniform particle distribution. The system is incorporated into a topical sunscreen matrix to improve sun protection and dermal retention. It achieves an in vitro sun protection factor (SPF) of approximately 32.9 and a skin deposition of approximately 65.2% daidzein. This corresponds to an approximately 3-fold and 3.8-fold improvement, respectively, compared to an otherwise identical, non-liposomal comparator product. This results in increased local efficacy while minimizing transdermal flow.

[0004] A QbD development approach defines critical quality characteristics such as vesicle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and photostability, and maps these to critical material and process parameters, such as the phospholipid-cholesterol ratio, aqueous phase composition, hydration and ultrasound profiles, and temperature control with regard to bilayer phase transitions. By maintaining vesicles below 200 nm and a low PDI, the system improves skin penetration and residence time while supporting the controlled release of daidzein as a photoprotective antioxidant, which also promotes collagen homeostasis. This enhances the sunscreen's performance beyond simple UV filtration (absorption / reflection). Detailed description

[0005] The system comprises a dispersion of unilamellar or oligolamellar liposomes consisting primarily of pharmaceutical-grade phosphatidylcholine and cholesterol. Stabilizing lipids or surface modifiers can be added optionally. Depending on the solubilization strategy, daidzein is encapsulated in the lipid bilayer and / or aqueous compartments. The vesicles are engineered to achieve a mean hydrodynamic diameter of approximately 197.9 nm and a polydispersity index (PDI) of approximately 0.17 (measured by dynamic light scattering) to ensure uniform distribution and predictable skin interaction. The zeta potential is adjusted to promote dermal retention without rapid clearance. The formulation is incorporated into a cosmetically compatible sunscreen base containing approved UV filters, emollients, humectants, rheology modifiers, and antioxidants.The liposomal fraction contributes to both increasing the sun protection factor (SPF) and localizing daidzein in the stratum corneum and vital epidermis.

[0006] The QbD risk assessment identifies vesicle size, polydispersity index (PDI), encapsulation efficiency, and photostability as critical quality attributes (CQAs). Material properties such as lipid purity, cholesterol ratio, and aqueous solution pH, as well as process parameters such as hydration temperature relative to the lipid phase transition, ultrasonic energy / time, and post-processing steps (e.g., extrusion, cold chain handling), are treated as critical process parameters (CPPs) with established design spaces. During experimental design, the molar ratios of lipid to cholesterol and the ultrasonic profiles are varied to minimize PDI while maintaining high daidzein loading and membrane integrity under simulated UV irradiation. This reduces rapid drug leakage and ensures uniform release.The resulting system exhibits a sun protection factor (SPF) of nearly 32.92, as measured using recognized in vitro SPF methods for cosmetic formulations. This represents an approximately threefold improvement over a comparable non-liposomal control, attributable to the synergistic UV filtering performance and the antioxidant effects of daidzein localized within the vesicles.

[0007] Skin deposition studies show that after standardized exposure, approximately 65.18% of the applied daidzein remains in the skin layers. This corresponds to approximately 3.8 times higher dermal retention compared to the non-liposomal comparator. These results are consistent with literature data showing that liposomal carriers can increase local residence time in the skin and reduce systemic permeation. The antioxidant and collagen-promoting properties of daidzein complement UV filters by limiting oxidative DNA damage and supporting matrix maintenance. This is comparable to the broader photoprotective mechanisms of polyphenols documented for natural ingredients. The vesicle size of approximatelyA micron size of 200 nm was chosen because submicron liposomes offer better dermal accessibility and a longer residence time compared to larger vesicles, while vesicles that are too small could risk deeper permeation. A low polydispersity index (PDI) ensures dense distribution and thus a reproducible effect.

[0008] The vesicles are manufactured by thin-film hydration or ethanol injection, followed by controlled sonication or extrusion to achieve the target size. The processing temperature is maintained below or near the lipid phase transition temperature to balance membrane fluidity and prevent premature leakage of the encapsulated active ingredients, particularly upon subsequent UV irradiation. The final product is filled into an airtight primary container and stored at a controlled temperature to maintain vesicle integrity. Stability tests include vesicle size / PDI drift, encapsulation retention, and SPF retention after accelerated aging and UV irradiation.The system is applied topically like a conventional sunscreen, but through daidzein release and higher skin deposition, it offers improved sun protection, providing both immediate UV filtering and additional biological protection against UV-induced oxidative and inflammatory processes.

[0009] In certain formulations, the surface is modified (e.g., with neutral or weakly cationic lipids) to optimize interaction with the lipids of the stratum corneum without increasing skin irritation. Antioxidant co-stabilizers protect both the lipids and daidzein from photodegradation, thus maintaining efficacy during sun exposure. Process controls and release specifications are consistent with the QbD documentation to ensure batch-to-batch reproducibility of critical quality attributes (CQAs). This includes acceptance criteria for vesicle size (approximately 198 nm), polydispersity index (PDI, approximately 0.17), encapsulation efficiency, and sun protection factor (SPF) within a statistically justified design space.

Claims

[1] A topical sunscreen composition consisting of daidzein-loaded liposomes embedded in a cosmetically acceptable sunscreen base, wherein the liposomes have a mean vesicle size of about 198 nm and a polydispersity index of about 0.17 and are configured to increase the in vitro sun protection factor (SPF) and skin deposition of daidzein compared to a non-liposomal formulation. [2] Composition according to claim 1, wherein a QbD framework defines critical quality features such as vesicle size, PDI, encapsulation efficiency and photostability and establishes a design space by controlling the lipid composition, cholesterol ratio, hydration temperature and the parameters of ultrasonic treatment or extrusion. [3] Composition according to claim 1, wherein the in vitro sun protection factor (SPF) under standardized test conditions is about 32.9 and the skin deposition of daidzein reaches about 65.2%. This corresponds to at least a threefold increase in SPF and about 3.8-fold higher dermal retention compared to a corresponding non-liposomal control group. [4] Composition according to claim 1, wherein the vesicle architecture and process conditions are selected such that UV-induced leakage is minimized and encapsulation is maintained during exposure. This ensures localized delivery of daidzein into the epidermal layers for improved sun protection.