Wound dressings loaded with an anti-inflammatory jucá (Libidibia ferrea) extract using supercritical carbon dioxide technology

Abstract

a b s t r a c t N-Carboxybutyl chitosan (CBC), collagen/cellulose (Promogran ® ) and hyaluronic acid-based (Hyalofill ® ) polymeric matrices/dressings were loaded with an extract obtained from jucá (Libidibia ferrea) and in order to develop wound dressings endowed with anti-inflammatory activity. Jucá fruits were subjected to supercritical fluid extraction (SFE) using CO 2 at 25 MPa and 50• C and the resulting extract was later incorporated into the above referred wound dressings by a supercritical fluid impregnation/deposition method (SSI). GC analysis revealed that the obtained SFE extract is particularly rich in unsaturated (52%) and saturated (26%) fatty acids as well as in terpenoids (13%) such as lupenone and gamma-sitosterol. Extract loading yields depended on the affinity of the hydrophobic extract for the specifically employed wound dressing material and was almost 2-fold greater for CBC than for the other two commercial wound dressings. The prepared extract-loaded dressings were cytocompatible with RAW 264.7 macrophages (viability > 85% at 24 h) and down-regulated the expression of TNF-␣ and IL-1␣ proinflammatory cytokines as well as the production of nitric oxide, which confirms the anti-inflammatory capacity of the employed jucá extract. Nevertheless, such effect was somehow counteracted by a proinflammatory activity that was exhibited by CBC. Prepared dressings presented a wide range of water vapor ((2.9-14.7) × 10 14 kg/(s m Pa)) and oxygen permeability (150 up to 830 barrer) which make them potentially suitable for the management of various wound types at different healing stages.

Drug loading of polymer implants by supercritical CO 2 assisted impregnation: A review

“…On the contrary is noticed for hydrophobic compounds that prefer polymers with long alkyl-chains and presenting a strong hydrophobicity [36,85,86]. For example, hydrophobic extracts from juca fruits were found to be more loaded into N-carboxybutyl chitosan than into two other commercial dressings due to its higher hydrophobicity and to favorable interactions, thus increasing the partitioning coefficient of the molecules in this matrix [36]. In case of hydrogels, the presence of water in the matrix hinders the impregnation of hydrophobic drugs that prefer to stay in the scCO 2 phase [32].…”

“…Natu et al have shown that timolol maleate which is a hydrophilic drug is more impregnated in poly(ε-caprolactone) PCL blended with poly(oxyethylene-b-oxypropylene-b-oxyethylene) (PCL/POE) copolymer than in PCL blended with poly(ethylene-co-vinyl acetate) (PCL/ PEVA) copolymer because of the higher hydrophilicity of the first copolymer [44]. On the contrary is noticed for hydrophobic compounds that prefer polymers with long alkyl-chains and presenting a strong hydrophobicity [36,85,86]. For example, hydrophobic extracts from juca fruits were found to be more loaded into N-carboxybutyl chitosan than into two other commercial dressings due to its higher hydrophobicity and to favorable interactions, thus increasing the partitioning coefficient of the molecules in this matrix [36].…”

“…Generally, if the API has a poor affinity for the polymer it can be easily vented with CO 2 from the matrix. In that situation, high depressurization rate favor the entrapment of the API in the polymer [36,44,53]. On the contrary, for system with strong polymer/API interactions, slow depressurization rate should be chosen [62].…”

“…Antibacterial and anti-inflammatory compounds were impregnated into commercialized hydrogels of chitosan derivatives [29,[34][35][36], collagen/cellulose [36], hyaluronic acid [36] and agarose [34]. Once this dressing is applied on the wound, it should adsorb the exudates which should increase the swelling of the matrix and favor the release of the drug [34,36]. The original hydrogels were used as films or pre-foamed matrix before being impregnated.…”

Antileishmanial activity of extracts from Libidibia ferrea: development of in vitro and in vivo tests

“…Among the chemical components described in the literature for the genus Libidibia the presence of polyphenols is highlighted. Another class of substances that have been characterized are terpenoids, which are usually extracted with low polarity solvents (Dias et al 2013). …”