Evaluation of the Healing Effect of Ointments Based on Bee Products on Cutaneous Lesions in Wistar Rats.

The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three apitherapy products. The ointments were applied topically for 21 days. Clinical and macroscopic evaluation was performed throughout the experiment, with the recording of the re-epithelialization period and determination of the wound contraction rate on days 6 and 9. The histopathological examination was performed on days 1, 3, 12 and 21 of the treatment. The topical formulations were also characterized from a rheological point of view in order to verify their stability. HPLC analysis of propolis revealed the presence of phenolic compounds, particularly ferulic acid and p-coumaric which were found in high amounts. All ointments had beneficial effects on wound contraction and the re-epithelialization period, but the most significant result, both macroscopically and especially in terms of histological architecture, was presented by the ointment that contains all three apitherapy products, due to their synergistic effect.

Polysaccharides-Based Complex Particles' Protective Role on the Stability and Bioactivity of Immobilized Curcumin.

The curcumin degradation represents a significant limitation for its applications. The stability of free curcumin (FC) and immobilized curcumin in complex particles (ComPs) based on different polysaccharides was studied under the action of several factors. Ultraviolet-visible (UV-VIS) and Fourier-transform infrared (FTIR) spectroscopy proved the FC photodegradation and its role as a metal chelator: 82% of FC and between 26% and 39.79% of curcumin within the ComPs degraded after exposure for 28 days to natural light. The degradation half-life (t1/2) decreases for FC when the pH increases, from 6.8 h at pH = 3 to 2.1 h at pH = 9. For curcumin extracted from ComPs, t1/2 was constant (between 10 and 13 h) and depended on the sample's composition. The total phenol (TPC) and total flavonoids (TFC) content values increased by 16% and 13%, respectively, for FC exposed to ultraviolet light at λ = 365 nm (UVA), whereas no significant change was observed for immobilized curcumin. Antioxidant activity expressed by IC50 (µmoles/mL) for FC exposed to UVA decreased by 29%, but curcumin within ComPs was not affected by the UVA. The bovine serum albumin (BSA) adsorption efficiency on the ComPs surface depends on the pH value and the cross-linking degree. ComPs have a protective role for the immobilized curcumin.

Hydrogel Films Based on Chitosan and Oxidized Carboxymethylcellulose Optimized for the Controlled Release of Curcumin with Applications in Treating Dermatological Conditions.

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO4 were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH2 groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups' presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups' conversion index value increased when the -CHO/-NH2 molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (REf%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH2 increases. The curcumin REf% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films' antioxidant activity was improved due to the CS presence.

Drug Delivery System Based on pH-Sensitive Biocompatible Poly(2-vinyl pyridine)-b-poly(ethylene oxide) Nanomicelles Loaded with Curcumin and 5-Fluorouracil.

Smart polymeric micelles (PMs) are of practical interest as nanocarriers for the encapsulation and controlled release of hydrophobic drugs. Two hydrophobic drugs, naturally-based curcumin (Cur) and synthetic 5-fluorouracil (5-FU), were loaded into the PMs formed by a well-defined pH-sensitive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP90-b-PEO398) block copolymer. The influence of the drug loading on the micellar sizes was investigated by dynamic light scattering (DLS) and it appears that the size of the PMs increases from around 60 to 100 nm when Cur is loaded. On the contrary, the loading of the 5-FU has a smaller effect on the micellar sizes. This difference can be attributed to higher molar mass of Cur with respect to 5-FU but also to higher loading efficiency of Cur, 6.4%, compared to that of 5-FU, 5.8%. In vitro drug release was studied at pH 2, 6.8, and 7.4, and it was observed that the pH controls the release of both drugs. At pH 2, where the P2VP sequences from the "frozen-in" micellar core are protonated, the drug release efficiencies exceed 90%. Moreover, it was demonstrated, by in vitro assays, that these PMs are hemocompatible and biocompatible. Furthermore, the PMs protect the Cur against the photo-degradation, whereas the non-ionic PEO corona limits the adsorption of bovine serum albumin (BSA) protein on the surface. This study demonstrates that these pH-sensitive PMs are suitable for practical utilization as human-safe and smart, injectable drug delivery systems.

Curcumin-loaded polysaccharides-based complex particles obtained by polyelectrolyte complexation and ionic gelation. I-Particles obtaining and characterization.

Curcumin has essential therapeutic benefits, but it is insoluble in water and thus has low bioavailability. This study aimed to immobilize curcumin into new polysaccharide-based microparticles (gellan, i-carrageenan, and chitosan) to increase its stability and bioavailability. Curcumin-loaded complex microparticles were obtained from three polysaccharides, of different ionic character, by ionic cross-linking and polyelectrolyte complexation. The immobilization efficiency was between 85.75% and 97.25%. The microparticles were characterized morphologically by SEM, and it was observed that the microparticles containing the i-carrageenan had a more pronounced porosity of the matrix. The swelling degree values at pH = 7.4 were superior to those obtained at pH = 6.8 or pH = 2 and depend on both the cross-linking degree and particles morphology. The polysaccharides microparticles, curcumin, and constituent polysaccharides were characterized by FT-IR spectroscopy. The curcumin release kinetics was studied in three different pH media, and the release efficiency ranged between 65.1% and 97.9% at pH = 7.4, between 60.2% and 82.2% at pH = 6.8 and between 56.1% and 64.0% at pH = 2. These microparticles can be intended for oral administration, having as therapeutic target the colon, for the controlled release of curcumin, since they can overcome the gastric barrier without the degradation of the active principle, which is protected by the polymer matrix.

Yeast cells immobilized in spherical gellan particles cross-linked with magnesium acetate.

In this paper we report on the production of microbioreactors using ionically cross-linked gellan containing immobilized yeast cells with potential application in glucose fermentation. Cross-linking was achieved through a novel extrusion process in capillary by ionotropic gelation under the action of magnesium acetate. Compared to commonly used methods, this provides a host of practical advantages. The particles were physico-chemically and morphologically characterized as their mechanical stability, behavior in aqueous media, and bio-catalytic activity are influenced by the amount of cross-linker used. This demonstrated their ability to be reused in a large number of fermentation cycles without losing their bio-catalytic activity. Our results are wholly comparable with the behavior of free yeast. We show that fermentation cycles can succeed either immediately or at variable intervals, ensuring high yields of glucose transformation, comparable-if not superior-to results currently obtained using free yeast.