Nanostructured Lipid Carriers (NLC)-Based Topical Formulation of Hesperidin for Effective Treatment of Psoriasis
Abstract
Background: Various routes of drug administration are available for psoriasis treatment. However, there is an urgent need for novel and improved therapeutic options. Hence, our study aimed to develop a nanostructured lipid carrier (NLC) gel of hesperidin (HPD) using a systemic QbD approach for an effective treatment of psoriasis.
Methods: Initially, HPD-NLC was optimized with independent variables (drug content, amount of liquid lipid, total lipid, and surfactant concentration) using Box–Behnken Design to assess dependent variables (particle size, size distribution, and entrapment efficiency). HPD-NLC was developed using the high-shear homogenization technique. The characteristics of nanoformulation such as particle size, morphology [transmission electron microscopy (TEM) and differential scanning calorimetry (DSC)], crystallinity [powder X-ray diffraction (XRD)], and chemical interactions [Fourier transform infrared spectroscopy (FTIR)], the drug entrapment efficiency (%EE), and the drug release were investigated. Franz-diffusion cell was utilized to perform in vitro diffusion study, and an imiquimod-induced psoriasis model was used for in vivo study.
Results: The optimized HPD-NLC exhibited a spherical shape with particle size of 125.7 nm, polydispersity index (PDI) of 0.36, and entrapment efficiency of 52.26% w/w. Further, different techniques validated the reduced crystallinity of the hesperidin. The in vitro diffusion study highlighted the sustained and anomalous diffusion of the drug from NLC gel. In the in vivo study, the HPD-NLC-Gel-treated group displayed normal skin with minimal keratosis, while the drug-loaded gel group exhibited signs of hyperkeratosis and parakeratosis signs.
Conclusions: HPD-NLC gel showed promising advancement in nanotechnology-based psoriasis treatment and the results of this study open the door for the application of topical HPD-NLC-Gel clinically.
Introduction
Chronic, immune-mediated skin illness, known as psoriasis, can cause severe morbidity and mortality due to epidermal keratinocyte hyperproliferation and poor differentiation. Effective psoriasis treatment can lead to the restoration of skin to a clinically normal state, characterized by the resolution of epidermal thickness and a reduction of inflammation [1,2]. Approximately eighty percent of psoriasis patients have intense to moderate signs and symptoms, which are treated with topical medications. Those with more advanced disease are typically treated with phototherapy and systemic therapies. It is still recommended to treat psoriasis with topical medication due to its integral advantages, which include less systemic toxicity, enhanced patient compliance, and localized therapeutic impact [3]. The primary limitation of topical therapies is inadequate drug penetration through scaly psoriatic skin. For this reason, the discovery of a novel carrier system for treatment that can deliver a therapeutic amount of drug into the psoriasis-affected tissues is now underway [4].
Hesperidin (HPD) is a flavanone glycoside found naturally present in all citrus fruits. Research has demonstrated that HPD has inhibitory effects on keratinocyte proliferation and exhibits anti-psoriatic properties in murine models with imiquimod-induced psoriasis-like dermatitis [5]. Oral formulations of HPD have not worked well because of its low solubility with limited absorption. The bioavailability of many oral medications often poses challenges due to inadequate solubility, low dissolution rates, and an absence of proportionality in dosages [6]. When patients are obliged to adhere to a frequent dosing schedule for an extended duration of treatment, they typically stop complying with the prescribed therapy. Lipid nanoparticle systems are typically preferred for dermal treatment because they aid in the medication fragment’s operative retention and permeation to the skin and have a greater capacity to entrap drug particles within lipid layers [7,8].
Innovative nanotechnology has been employed to meet the objective of safe and efficacious psoriasis therapy. New topical transporters have been tested to improve skin permeation, including microemulsion, niosomes, nanogel, deformable liposomes, liposomal hydrogel, and solid lipid nanoparticles (SLNs). However, these carriers often face challenges such as low medication encapsulation efficiency, drug instability during storage, and high water content in the formulations. Research on topical and cosmetic treatments utilizing nanostructured lipid carriers (NLC) has gained attention, as these systems effectively address critical problems associated with other nanocarriers. NLC is a second generation of solid lipid nano-compartments stabilized by surfactants, encapsulated in a solid lipid matrix that is spatially incompatible. They enhance the drug loading by preventing the premature release of the encapsulated drug due to its imperfect crystal structure. Furthermore, when applied topically, NLCs improve skin emollience and penetration by providing the skin with deeper hydration [9]. Additionally, NLCs can encapsulate drugs in their molecular state or as amorphous clusters and adhere well to the skin, forming thin films that create an occlusive effect, thereby reducing the transepidermal water loss [10,11]. The current research work aimed to develop an HPD-loaded NLC gel and evaluate its potential in an animal model of psoriasis. A Box–Behnken Design (BBD) was employed to optimize the HPD-NLC formulation. By dissolving the HPD-NLC in the gel base, the HPD-loaded NLC gel was formulated and characterized. The effectiveness of the gel in treating imiquimod-induced psoriasis in Wistar rats was assessed based on histological analysis and the psoriatic area and severity index (PASI) score
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Materials
Hesperidin was received as a gift from Harveer Herbal Pharma, Ludhiana, India. Compritol® 888 ATO was obtained from Gattefosse India Private Limited, Mumbai, India. Tween 80, Oleic acid, Hydroxy propyl methyl cellulose (HPMC) K4M, Carbopol 934, acetone, and dichloromethane were purchased from Loba Chemicals Private Limited, Mumbai, India. Imiquad™ cream (Glenmark, Goa, India) was used to induce psoriasis. All the chemicals used in this study were of analytical grade.
Rani, A.; Kaur, R.; Aldahish, A.; Vasudevan, R.; Balaji, P.; Dora, C.P.; Chandrasekaran, B.; Singh, T.G.; Sharma, R. Nanostructured Lipid Carriers (NLC)-Based Topical Formulation of Hesperidin for Effective Treatment of Psoriasis. Pharmaceutics 2025, 17, 478. https://doi.org/10.3390/pharmaceutics17040478
Read also our introduction article on Lipid Nanoparticles here:
