Gianina Dodi

Chemical functionalization of hyaluronic acid for drug delivery applications

Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H(1) NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications.

Silica nanoparticles: preparation, characterization and in vitro/in vivo biodistribution studies.

BACKGROUND The current progress in pharmaceutical nanotechnology field has been exploited in the design of functionalized radiolabelled nanoparticles that are able to deliver radionuclides in a selective manner to improve the outcome of diagnosis and treatment. Silica nanoparticles (SNPs) have been widely developed for biomedical applications due to their high versatility, excellent functional properties and low cost production, with the possibility to control different topological parameters relevant for multidisciplinary applications. PURPOSE The aim of the present study was to characterize and evaluate both in vitro, by microscopy techniques, and in vivo, by scintigraphic imaging, the biodistribution of silica nanostructures derivatives (Cy5.5 conjugated SNPs and (99m)Tc radiolabelled SNPs) to be applied as radiotracers in biomedicine. METHODS SNPs were synthesized by hydrolysis and condensation of silicon alkoxides, followed by surface functionalization with amino groups available for fluorescent dye and radiolabelling possibility. RESULTS Our data showed the particles size distribution (200-350 nm), the surface charge (negative for bare and fluorescent SNPs and positive for amino SNPs), polydispersity index (broad distribution), the qualitative composition and the toxicity assessments (safe material) that made the obtained SNPs candidates for in vitro/in vivo studies. A high uptake of fluorescent SNPs in all the investigated organs was evidenced by confocal microscopy. The (99m)Tc radiolabelled SNPs biodistribution was quantified in the range of 12-100% counts/g organ using the scintigraphic images. CONCLUSIONS The obtained results reveal improved properties, namely, reduced toxicity with a low level of side effects, an improved biodistribution, high labelling efficiency and stability of the radiolabelled SNPs with potential to be applied in biomedical science, particularly in nuclear medicine as a radiotracer.

Flaxseed lignan wound healing formulation: Characterization and in vivo therapeutic evaluation

Flaxseed lignans are a natural source of useful biologically active components that show a diverse spectrum of health-promoting properties. The valuable effects of the phenolic molecules are mainly due to their antioxidant activity by preventing oxidative stress and stimulate collagen synthesis, therefore, providing benefits to the skin. The present work highlights the development of flaxseed extract formulation as novel wound healing agent. The recognition of key structural features within flaxseed extract was crucial for the design and development of the therapeutic cream. Chromatographic analyses were employed for bioactive compounds identification and quantification. Folin-Ciocalteu method determined the total phenolic content and the antioxidant properties were evaluated by DPPH assay. The storage and loss modulus and tan δ were calculated for cream rheological properties evaluation. In vitro diffusion capacity and in vivo wound healing activity of phenolic cream were evaluated on Wistar rats. The collective properties and healing effect of the flaxseed suggested wound healing capacity.

Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations.

Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers.

Biosynthesis of dextran by Weissella confusa and its In vitro functional characteristics

The aim of this study was to monitor the influence of the fermentation conditions on the exopolysaccharides (EPS) biosynthesis. For this, different culture media compositions were tested on an isolated lactic acid bacteria (LAB) strain, identified by 16S rDNA sequence as being Weissella confusa. It was proved that this bacterial strain culture in MRS medium supplemented with 80g/L sucrose and dissolved in UHT milk produced up to 25.2g/L of freeze-dried EPS, in static conditions, after 48h of fermentative process. Using FTIR and NMR analysis, it was demonstrated that the obtained EPS is a dextran. The thermal analysis revealed a dextran structure with high purity while GPC analysis depicted more fractions, which is normal for a biological obtained polymer. A concentration up to 3mg/mL of dextran proved to have no cytotoxic effect on normal human dermal fibroblasts (NHDF). Moreover, at this concentration, dextran breaks up to 70% of the biofilms formed by the Candida albicans SC5314 strain, and has no antimicrobial activity against standard bacterial strains. Due to their characteristics, these EPS are suitable as hydrophilic matrix for controlled release of drugs in pharmaceutical industry.

Medicinal Plants of the Family Lamiaceae in Pain Therapy: A Review

Recently, numerous side effects of synthetic drugs have lead to using medicinal plants as a reliable source of new therapy. Pain is a global public health problem with a high impact on life quality and a huge economic implication, becoming one of the most important enemies in modern medicine. The medicinal use of plants as analgesic or antinociceptive drugs in traditional therapy is estimated to be about 80% of the world population. The Lamiaceae family, one of the most important herbal families, incorporates a wide variety of plants with biological and medical applications. In this study, the analgesic activity, possible active compounds of Lamiaceae genus, and also the possible mechanism of actions of these plants are presented. The data highlighted in this review paper provide valuable scientific information for the specific implications of Lamiaceae plants in pain modulation that might be used for isolation of potentially active compounds from some of these medicinal plants in future and formulation of commercial therapeutic agents.