Block copolymers containing dextran and deoxycholic acid polyesters. Synthesis, self-assembly and hydrophobic drug encapsulation.

New biocompatible amphiphilic block copolymers were prepared using two natural compounds as starting materials, a polysaccharide (dextran) and a bile acid (deoxycholic acid). The copolymers were synthesized by dipolar 1,3-cycloaddition reaction between dextran with azide end groups and deoxycholic acid - oligo(ethylene glycol)s polyester with propargyl end groups. Different copolymer composition were obtained by variation of molecular weights of dextran (Mn 4.5, 8, 15 kDa) and polyester (Mn 2-6 kDa), as well as the length of oligo(ethylene glycol) (2-4 ethylenglycol units) used for polyester synthesis. These copolymers can for micelle like aggregates in aqueous medium with nanometric size (50-600 nm) and spherical form, as assessed by light scattering, atomic force microscopy and transmission electron microscopy. Encapsulation of the hydrophobic drug curcumin in micelles could increase 68,181 times its water solubility, and curcumin release from micelles was slow and with reduced burst effect.

Antimicrobial activity of chemically modified dextran derivatives.

Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60µg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C12H25 or C18H37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups.

New shell crosslinked micelles from dextran with hydrophobic end groups and their interaction with bioactive molecules.

Micelles formed in aqueous solution by dextran with hydrophobic (alkyl) end-groups were stabilized through divinyl sulfone crosslinking of the dextran shell. The efficacy of the crosslinking reaction was influenced by the divinyl sulfone amount, the pH and micelle concentration. Crosslinked micelles with a moderate crosslinking degree were further functionalized by attachment of 10 and 17 moles% N-(2-hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups along the dextran chain. The size and shape of both crosslinked micelles and their cationic derivatives were analyzed by DLS and TEM. The prepared micelles were able to bind anionic diclofenac (60-370 mg/g), hydrophobic anionic indometacin (70-120 mg/g), and hydrophobic alpha-tocopherol (170-220 mg/g) or ergocalciferol (90-110 mg/g) by hydrophobic or/and electrostatic forces. The release experiments and the antioxidant activity of bound alpha-tocopherol highlighted the potential of the new nano-sized micelles mainly as carriers for prolonged and controlled delivery of hydrophobic drugs.

Micelle-like association of polysaccharides with hydrophobic end groups.

New dextran derivatives with hydrophobic end groups were synthesized by reductive amination of dextran chain ends, followed by chemical modification of the dextran main chain by attachment of cationic groups and/or by crosslinking. Properties of the aggregates formed by hydrophobic association of the end groups were studied by fluorescence, dynamic light scattering, atomic force microscopy and transmission electron microscopy and depended on the length of the dextran chain (6, 10, 25 kDa) and the hydrophobicity of the end group (alkyl, dialkyl, bile acid). All neutral derivatives were able to form micelle-like aggregates above a critical aggregation concentration (0.008-0.159 g/dL). Polarity of the micelle hydrophobic core was close to or lower than that of neutral low molecular surfactants (polarity parameter I1/I3≈0.8-1.13), aggregation number was 20-30 and hydrodynamic radius 20-30 nm. Attachment of cationic groups to the dextran main chain increased critical aggregation concentration and core polarity, but cationic polymeric surfactants with good association ability could be obtained by an appropriate choice of the content and hydrophobicity of the cationic groups. Cross-linking of the micelle shell with divinylsulfone increased micelle stability to dilution.