Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-κ-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 ± 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin’s bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals.

Films based on carrageenan, alginate and poloxamer 407 have been formulated with the main aim to apply prepared formulations in wound healing process. The formulated films were loaded with diclofenac, an anti-inflammatory drug, as well as diclofenac and curcumin, as multipurpose drug, in order to enhance encapsulation and achieve controlled release of these low-bioavailability compounds. The obtained data demonstrated improved drug bioavailability (encapsulation efficiency higher than 90%), with high, cumulative in vitro release percentages (90.10% for diclofenac, 89.85% for curcumin and 95.61% for diclofenac in mixture-incorporated films). The results obtained using theoretical models suggested that curcumin establishes stronger, primarily dispersion interactions with carrier, in comparison with diclofenac. Curcumin and diclofenac-loaded films showed great antibacterial activity against Gram-positive bacteria strains (Bacillus subtilis and Staphylococcus aureus, inhibition zone 16.67 and 13.67 mm, respectively), and in vitro and in vivo studies indicated that curcumin- and diclofenac-incorporated polymer films have great potential, as a new transdermal dressing, to heal wounds, because diclofenac can target the inflammatory phase and reduce pain, whereas curcumin can enhance and promote the wound healing process.

The ¹H nuclear magnetic resonance spectroscopy was applied to study the reaction of the dipeptide glycyl-d,l-methionine (H-Gly-d,l-Met-OH) and its N-acetylated derivative (Ac-Gly-d,l-Met-OH) with hydrogen tetrachloridoaurate(III) (H[AuCl₄]). The corresponding peptide and [AuCl₄]^– were reacted in 1:1, 2:1, and 3:1 molar ratios, and all reactions were performed at pD 2.45 in 0.01 M DCl as solvent and at 25°C. It was found that the first step of these reactions is coordination of Au(III) to the thioether sulfur atom with formation of the gold(III)-peptide complex [AuCl₃(R-Gly-Met-OH-S)] (R=H or Ac). This intermediate gold(III) complex further reacts with an additional methionine residue to generate the R-Gly-Met-OH chlorosulfonium cation as the second intermediate product, which readily undergoes hydrolysis to give the corresponding sulfoxide. The oxidation of the methionine residue in the reaction between H-Gly-d,l-Met-OH and [AuCl₄]^– was five times faster (k ₂ = 0.363 ± 0.074 M^-1s^-1) in comparison to the same process with N-acetylated derivative of this peptide (k ₂ = 0.074 ± 0.007 M^-1s^-1). The difference in the oxidation rates between these two peptides can be attributed to the free terminal amino group of H-Gly-d,l-Met-OH dipeptide. The mechanism of this redox process is discussed and, for its clarification, the reaction of the H-Gly-d,l-Met-OH dipeptide with [AuCl₄]^– was additionally investigated by UV-Vis and cyclic voltammetry techniques. From these measurements, it was shown that the [AuCl₂]^– complex under these experimental conditions has a strong tendency to disproportionate, forming [AuCl₄]^– and metallic gold. This study contributes to a better understanding of the mechanism of the Au(III)-induced oxidation of methionine and methionine-containing peptides in relation to the severe toxicity of anti-arthritic and anticancer gold-based drugs.