Development of a nanostructured lipid carrier for transdermal delivery of ketoprofen: optimization of encapsulation, in vitro studies of skin permeation and anti-inflammatory efficacy.

• Grant number: 25/05481-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Ricardo Kenji Ohno Takaki
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

Nanostructured lipid carriers (NLCs) have attracted great interest in the pharmaceutical field due to their structure composed of a combination of liquid and solid lipids, which improve the encapsulation of various factors, especially fat-soluble ones, making them effective in different therapeutic proposals. These nanoparticles have stood out mainly in topical and transdermal administration, which have several advantages over other routes of administration. Ketoprofen (CT), a drug widely used in the treatment of inflammatory disorders such as muscle inflammation, rheumatoid arthritis, among others. However, it presents several side effects when used chronically. A promising approach to reduce adverse effects is the transdermal administration of the drug. The objective of this study is to develop a NLC containing CT by the hot homogenization method followed by sonication. As an approach to increase the encapsulation of CP and, because this molecule is a weak acid, the variation in pH in the process of obtaining NLCs can influence the encapsulation rate of CT. After obtaining the NLC containing CT, the obtained dispersion will be dialyzed with buffer at pH=7.0, followed by characterization of colloidal properties, such as size, polydispersity index (PdI), zeta potential, particle concentration and encapsulation efficiency of CT. In vitro release studies will be conducted using a synthetic cellulose membrane to determine the release kinetics of CT. In addition, in vitro skin permeation studies will be performed using dermatomized pig ear skin in Franz vertical cell. Cytotoxicity tests will be performed on immortalized murine macrophage cells (Raw264.7) to evaluate the cellular viability of the treatment with NLC-CT. Subsequently, efficacy studies will be conducted on cells stimulated with lipopolysaccharide to simulate an inflammatory process and treated with NLC-CT. The anti-inflammatory activity will be evaluated by quantifying the pro-inflammatory mediator tumor necrosis factor alpha (TNF-¿) by ELISA. These studies aim to optimize the nanoencapsulation of CT in CLN and enable the transdermal release of CT as an effective and safe strategy for the transdermal delivery of CT, with the potential to improve the treatment of inflammatory conditions and minimize the adverse effects associated with the chronic use of this drug. (AU)