Topical formulation of quercetin encapsulated in natural lipid nanocarriers: Evaluation of biological properties and phototoxic effect

Author(s)

Pivetta, Thais P. ^[1] ; Silva, Leticia B. ^[1] ; Kawakami, Camila M. ^[2] ; Araujo, Margarete M. ^[1] ; Del Lama, Maria Perpetua F. M. ^[3] ; Naal, Rose Mary Z. G. ^[3] ; Maria-Engler, Silvya S. ^[4] ; Gaspar, Lorena R. ^[2] ; Marcato, Priscyla D. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Nanobiolab, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Pharmaceut Sci Dept, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Clin & Toxicol Anal Dept, Sch Pharmaceut Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 53, OCT 2019.
• Web of Science Citations: 1

Abstract

Skin aging might happen due to extrinsic and intrinsic factors that usually can induce the increase of free radicals and generate oxidative stress, which lead to skin alterations. Thus, there is a search for antioxidant substances that can control these effects. Quercetin (QT) is a flavonoid with antioxidant potential however presents poor percutaneous permeation, low stability and phototoxicity. Therefore, the encapsulation in nanoparticles is an interesting strategy to overcome these challenges. Nanostructured lipid carriers (NLC) is a promising type of vehicle that can improve drug penetration on skin and enhance the entrapment efficiency as well as improve the drug stability. These nanoparticles can be produced using natural lipids with biological properties resulting in a carrier with biological activities. The aim of this study was to produce NLC to load QT enhancing its permeation and obtaining an effective and safe topical formulation. The NLC were characterized regarding their size, zeta potential, entrapment efficiency, thermal behavior, morphology and evaluation of the biological properties using in vitro methods to analyze the antioxidant activity, skin permeation, antiallergic potential, cytotoxicity and phototoxicity potential on monolayer (HaCaT cells and 3T3 NRU PT) and on reconstructed human skin model (H3D-PT). The average size of QT-NLC was 130 nm with low polydispersity index (PdI) (similar to 0.260), and negative zeta potential (around of -13 mV). Through the thermal behavior analysis, the nanoparticle exhibited a low recrystallization index (13.03%), which is important to obtain high entrapment efficiency (97.42%) and avoid drug expulsion during the storage time. The nanoparticles showed a homogeneous morphology and were very stable regarding to size and PdI over to 120 days. On terms of biological properties QT-NLC presented antioxidant activity, enhanced penetration of quercetin in the skin and showed an antiallergic potential. Furthermore, in the reconstructed human skin model that consider viable epidermis bioavailability due to the presence of stratum corneum, it was observed that the topical formulation of QT-NLC presented no phototoxic potential. Therefore, the developed nanostructure is a vehicle with potential for topical administration of quercetin. (AU)

• FAPESP's process: 08/57805-2 - Institute of Bioanalytics
• Grantee: Lauro Tatsuo Kubota
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 16/07596-4 - Encapsulation of thymol in nanostructured lipid carriers composed of natural lipids
• Grantee: Thais Priscilla Pivetta
• Support type: Scholarships abroad - Research Internship - Scientific Initiation
• FAPESP's process: 13/24413-2 - Development of nanostructured lipid carrier of Illipe butter and Calendula oil as a quercetin encapsulation system: physico-chemical and biological evaluation
• Grantee: Thais Priscilla Pivetta
• Support type: Scholarships in Brazil - Scientific Initiation