Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation.

Giuliana Mancini,Helena Margarida Ribeiro,Lídia M D Gonçalves,Filomena A Carvalho,Joana Marto,Sandra Simões,António J Almeida

doi:10.3390/pharmaceutics13030328

Giuliana Mancini, Helena Margarida Ribeiro + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics13030328

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Journal: Pharmaceutics	Publication Date: Mar 3, 2021
Citations: 13	License type: CC BY 4.0

Affiliation: University of Lisbon, Laboratório Edol (Portugal)

Abstract

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.

Highlights

Non-steroidal anti-inflammatory drugs (NSAIDs) are topically applied to intact skin to treat painful inflammatory disorders, reaching effective concentrations in the tissues underlying the application site and even in the synovial fluid of joints
Different amounts of the studied drugs were incorporated into solid lipid nanoparticles (SLNs) in order to evaluate the effect of the initial drug concentration on the particle size distribution and zeta potential values, as well as on the incorporation parameters (Figure 2)
Different amounts of the studied drugs were incorporated into SLNs in order to eval8 of 23 uate the effect of the initial drug concentration on the particle size distribution and zeta potential values, as well as on the incorporation parameters (Figure 2)

Summary

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are topically applied to intact skin to treat painful inflammatory disorders, reaching effective concentrations in the tissues underlying the application site and even in the synovial fluid of joints. NSAIDs are widely prescribed for topical treatments in a variety of dosage forms, such as creams, gels lotions, sprays, and medicated plasters. These formulations have low skin permeation and may cause skin irritation that limits their extended use [2]. To overcome these drawbacks, advanced topical dosage forms have been proposed, including liposomes, transfersomes, and polymeric and lipid-based nanoparticles [3,4].

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