Soya lecithin–PLGA based hybrid nanocomposite enhances resveratrol delivery for psoriasis treatment and management

Abstract

Psoriasis is a chronic, autoimmune-driven inflammatory skin disorder characterized by red, scaly lesions, keratinocyte hyperproliferation, and infiltration of inflammatory cells. Current therapies, such as corticosteroids, are often limited by adverse effects, poor skin penetration, and low patient compliance, highlighting the need for more effective and safer topical delivery systems. Resveratrol (RSV), a plant-derived polyphenol from Vitis vinifera L., exhibits promising anti-inflammatory and antioxidant properties for psoriasis treatment. However, its clinical utility is restricted due to poor solubility, instability, and low skin permeability.

To overcome these challenges, resveratrol-loaded dual-carrier conjugated nanoparticles (RSVNPL) were developed using biocompatible soya lecithin and PLGA. These nanoparticles were further incorporated into a carbomer 974P-based hydrogel to form the resveratrol nanocomposite hydrogel (RSVNPGel), aimed at enhancing ease of application and skin residence time. The formulation exhibited improved physicochemical characteristics, including enhanced spreadability, adhesiveness, and storage stability. permeation studies showed significantly greater RSV accumulation in both epidermis and dermis compared to free RSV gel. In an imiquimod-induced psoriatic mice model, RSVNPGel demonstrated marked therapeutic benefits, including reduced epidermal thickness, inflam matory cell infiltration, and suppression of hallmark histopathological features.

PASI scoring confirmed sub stantial improvement in severity indices over the disease control. Additionally, serum biochemical markers (ALT, AST, creatinine) remained within normal limits, and organ histology confirmed systemic safety. Overall, RSVNPGel offers a sustainable, plant-based nanocarrier platform for effective and safe topical management of psoriasis. It enhances RSV skin delivery, minimises systemic exposure, and aligns with green pharmaceutical design principles.

Introduction

Psoriasis is a chronic autoimmune abnormal skin condition presented with thick, scaly, dry skin, along with abnormal epidermal differentiation, inflammation, infiltration of inflammatory cells and angiogenesis, affecting approximately 2–3 % of the global population (Damiani et al., 2021). It can develop at any age, mainly with two distinct peaks of onset: one typically occurring between the ages of 15 and 20 and another between 55 and 60 years (Nair and Badri, 2023). Although the precise causes and mechanisms are not fully understood, it is hypothesised that the IL-23/IL-17 pathway is crucial in driving keratinocyte hyperproliferation and abnormal differentiation, leading to psoriatic lesions. Significant immune cell infiltration has been observed, particularly in the dermis, with proliferating macrophages and T cells contributing to the inflammatory response. Among these, T cells release cytokines that initiate the inflammatory responses, for example, TNF-α, IL-17, and IL-22, further exacerbating disease progression (Zhang et al., 2023; Chiricozzi et al., 2011; Costache et al., 2022; Jang et al., 2021; Voglis et al., 2018).

Treatment options for psoriasis may vary based on severity and response to therapy. However, topical treatments are widely used, including corticosteroids, calcipotriol, and combination therapy, for mild to moderate cases (Keshari et al., 2023, Kim et al., 2017). (Torsekar and Gautam, 2017). For more severe cases or when topical treatments are ineffective, systemic drugs, which include acitretin, methotrexate, cyclosporine and biologics, are prescribed (Gisondi et al., 2017). However, many of these treatments come with significant side effects, particularly skin irritation, redness, burning and blistering, while long-term use raises concerns like toxicity, immunosuppression, and increased susceptibility to infections. These challenges necessitate exploring alternative, targeted, and safer treatment modalities.

Nanotechnology has emerged as a promising medical platform, significantly improving the delivery of various therapeutic agents, including hydrophobic and hydrophilic drugs, small-molecule drugs, genes, RNAs, and peptides (Azad and Chandra, 2025, Azad and Chandra, 2023). It also offers promising advancements in improving the therapeutic effectiveness and pharmacokinetics of many drugs (Chandra and Pandey, 2020; Mahato et al., 2020; Neekhra et al., 2024; Mitchell et al., 2020; Zhang et al., 2008). Lipid-polymer composite nanoparticles have recently gained substantial attention as advanced drug delivery systems that combine the advantages of both lipid and polymeric nanoparticles (Kumar et al., 2022). These hybrid structures form a polymer core enveloped by a lipid shell, which enhances drug stability, prevents premature leakage, and prolongs systemic circulation time. It offers high drug-loading capacity, controlled release, and precise targeting at tissue, cellular, and molecular levels, making it a highly effective and reliable drug-delivery platform (Alsaidan et al., 2023; Parveen et al., 2023; Mukherjee et al., 2019; Sivadasan et al., 2021; Gajbhiye et al., 2023, Soomherun et al., 2024).

Several studies have demonstrated the efficacy of lipid-polymer composite nanoparticles in psoriasis treatment by enhancing targeted drug delivery, improving drug stability, and controlling drug release (Desai et al., 2013, Keshari et al., 2025). For instance, lipid-polymer composite nanoparticles have been utilised to encapsulate the phosphodiesterase-4 inhibitor AN2728, enhancing its targeted delivery to psoriatic skin cells and improving therapeutic outcomes (Lin et al., 2021). Similarly, lipid-polymer composite nanoparticles have also been employed to deliver coenzyme Q10 (CoQ10), a potent antioxidant and anti-inflammatory agent for psoriasis treatment. By integrating the benefits of both lipid and polymer components, these nanoparticles provided enhanced drug stability and controlled release (Pukale et al., 2022a). Another promising approach involves encapsulating clobetasol propionate, a corticosteroid inside lipid-polymer composite nanoparticles; these nanoparticles facilitate deeper skin penetration, limited systemic exposure, and better therapeutic outcomes while significantly minimizing the potential for systemic adverse effects (Pukale et al., 2020). This carrier system can be used as a versatile platform for transporting various hydrophobic drugs like rapamycin for various skin disorders and has the potential for clinical and commercial use (Keshari et al., 2025).

In this study, as a lipid base, soya lecithin, a plant-derived phospholipid from Glycine max (L.) Merr. was used as a natural alternative. It provides excellent biocompatibility, enhances drug encapsulation, and enhances interaction with the lipid-rich stratum corneum, promoting better skin permeation (Courant et al., 2017, Ding et al., 2015; Godoy et al., 2015; Tian et al., 2012). Similarly, for a polymer base, poly(lactic-co-glycolic acid) (PLGA), a well-known biodegradable and FDA-approved copolymer, was used as the structural polymer matrix to ensure nanoparticle stability and enable controlled, sustained release of resveratrol (Keshari et al., 2025; Ravikumar et al., 2019; Szulc-Musioł and Sarecka-Hujar, 2021). As a therapeutic moiety, Resveratrol (RSV), a naturally occurring polyphenol compound found in plants including grapes (Vitis vinifera L.), berries (Vaccinium corymbosum L.), and peanuts (Arachis hypogaea L.), has demonstrated significant therapeutic potential in alleviating psoriasis-related inflammation(Stewart et al., 2023). Studies indicate that RSV activates the sirtuin 1 (SIRT1) pathway to inhibit aquaporin 3 (AQP-3), a key regulator of keratinocyte proliferation. This mechanism helps mitigate the excessive cell growth characteristic of psoriasis. Additionally, RSV exhibits potent antioxidant and anti-inflammatory properties, further supporting its role in psoriasis management. The topical application of RSV has shown promising effects due to its ability to penetrate the skin effectively, making it an attractive candidate for transdermal drug delivery (Wu et al., 2014). Despite its potential, clinical translation is hindered by its poor aqueous solubility, rapid metabolism, and limited bioavailability.

To overcome the existing limitations, a lipid-polymer composite nanoparticle system encapsulating RSV was developed to overcome the existing limitations, using plant-derived soya lecithin as the lipid component and biodegradable PLGA as the polymer base. These bio-based and biocompatible materials ensure a sustainable, safe, and effective drug delivery system aligned with green pharmaceutical design. Later, these nanoparticles were incorporated into a hydrogel system for easy application and long-lasting effect. By performing physicochemical characterisation, in vitro evaluations, ex vivo skin penetration studies, and in vivo efficacy assessments, the potential of RSV-loaded lipid-polymer composite was demonstrated as a novel, effective, and patient-friendly therapeutic approach for managing psoriasis topically. By utilising plant-sourced carrier systems and therapeutic agents, this formulation enhances drug stability and bioavailability and supports the development of environmentally responsible nanomedicine solutions.

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Materials

Soya lecithin (phosphatidylcholine derived from soybeans), phosphate-buffered saline (PBS, pH 7.4), and Dialysis membrane (12.5 kDa) were sourced from HiMedia. The poly(lactic-co-glycolic acid) (PLGA) copolymer, comprising a 50:50 molar ratio of DL-lactide to glycolide with a molecular weight ranging between 7,000 and 17,000 Da, was obtained from Nomisma Healthcare, India. Resveratrol (purity 98 %) was supplied by Zeta Scientific, India. Tween-80, trie thanolamine, and carbopol 974 P were procured from Sigma Aldrich, USA. Rhodamine 6 G (purity ≥97 %) was purchased from Merck KGaA, Germany. A 5 % w/w imiquimod cream was procured from Glenmark Pharmaceuticals, India. Throughout all experiments, high-purity deionized water (resistivity of 18.2 MΩ⋅cm) purified by Milli-Q Plus water purification system (Millipore, USA) was used.

Roshan Keshari, Rupali Bagale, Sulagna Rath, Swapnil Raut, Lokesh Kumar Bhatt, Abhijit De, Shamik Sen, Rohit Srivastava, Soya lecithin–PLGA based hybrid nanocomposite enhances resveratrol delivery for psoriasis treatment and management, Industrial Crops and Products, Volume 236, 2025, 121575, ISSN 0926-6690, https://doi.org/10.1016/j.indcrop.2025.121575.

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