Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation.
Giuliana ManciniLidia Maria GoncalvesJoana Marques MartoFilomena A CarvalhoSandra SimõesHelena Margarida RibeiroAntónio José AlmeidaPublished in: Pharmaceutics (2021)
Innovative formulations, including solid lipid nanoparticles (SLNs), have been sought to improve skin permeation of non-steroidal anti-inflammatory drugs (NSAIDs). The present study explores the use of SLNs, prepared using a fusion-emulsification method, to increase skin permeation and in vivo activity of two relevant NSAIDs: A liquid molecule (etofenamate) and a solid one (ibuprofen), formulated in a 2% hydroxypropyl methylcellulose gel through the gelation of SLN suspensions. Compritol® 888 ATO and Tween® 80 were used as a solid lipid and a surfactant, respectively. All production steps were up scalable, resulting in SLNs with high encapsulation efficiency (>90%), a mean particle size of <250 nm, a polydispersity index <0.2, and that were stable for 12 months. In vitro permeation, using human skin in Franz diffusion cells, showed increased permeation and similar cell viability in Df and HaCaT cell lines for SLN formulations when compared to commercial formulations of etofenamate (Reumon® Gel 5%) and ibuprofen (Ozonol® 5%). In vivo activity in the rat paw edema inflammation model showed that SLN hydrogels containing lower doses of etofenamate (8.3 times lower) and ibuprofen (16.6 times lower) produced similar effects compared to the commercial formulations, while decreasing edema and inflammatory cell infiltration, and causing no histological changes in the epidermis. These studies demonstrate that encapsulation in SLNs associated to a suitable hydrogel is a promising technological approach to NSAIDs dermal application.
Keyphrases
- anti inflammatory drugs
- wound healing
- oxidative stress
- sentinel lymph node
- induced apoptosis
- postoperative pain
- hyaluronic acid
- drug delivery
- single cell
- soft tissue
- photodynamic therapy
- squamous cell carcinoma
- fatty acid
- stem cells
- lymph node
- radiation therapy
- neoadjuvant chemotherapy
- cell cycle arrest
- endoplasmic reticulum stress
- cell proliferation