Deep Eutectic Solvent Formulations and Alginate-Based Hydrogels as a New Partnership for the Transdermal Administration of Anti-Inflammatory Drugs

abstract

The transdermal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is a valuable and safer alternative to their oral intake. However, most of these drugs display low water solubility, which makes their incorporation into hydrophilic biopolymeric drug-delivery systems difficult. To overcome this drawback, aqueous solutions of bio-based deep eutectic solvents (DES) were investigated to enhance the solubility of ibuprofen, a widely used NSAID, leading to an increase in its solubility of up to 7917-fold when compared to its water solubility. These DES solutions were shown to be non-toxic to macrophages with cell viabilities of 97.4% (at ibuprofen concentrations of 0.25 mM), while preserving the anti-inflammatory action of the drug. Their incorporation into alginate-based hydrogels resulted in materials with a regular structure and higher flexibility. These hydrogels present a sustained release of the drug, which is able, when containing the DES aqueous solution comprising ibuprofen, to deliver 93.5% of the drug after 8 h in PBS. Furthermore, these hydrogels were able to improve the drug permeation across human skin by 8.5-fold in comparison with the hydrogel counterpart containing only ibuprofen. This work highlights the possibility to remarkably improve the transdermal administration of NSAIDs by combining new drug formulations based on DES and biopolymeric drug delivery systems.

keywords

CONTROLLED-RELEASE; SKIN PENETRATION; IBUPROFEN; SOLUBILITY; DELIVERY; PERMEATION; DESIGN; HYDROCHLORIDE; ENHANCEMENT; COSOLVENTS

subject category

Pharmacology & Pharmacy

authors

Pedro, SN; Mendes, MSM; Neves, BM; Almeida, IF; Costa, P; Correia-Sa, I; Vilela, C; Freire, MG; Silvestre, AJD; Freire, CSR

Groups

G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

acknowledgements

This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC) and iBiMed UIDB/04501/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement This work was also financed by national funds from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB. FCT is also acknowledged for the doctoral grant (SFRH/BD/132584/2017) to S.N.P. and the research contracts under Scientific Employment Stimulus to C.V. (CEECIND/00263/2018 and 2021.01571.CEECIND) and C.S.R.F. (CEECIND/00464/2017).