Cyclodextrins and chitosan derivatives in sublingual delivery of low solubility peptides: A study using cyclosporin A, alpha-cyclodextrin and quaternary chitosan N-betainate.

Systemic drug delivery through intraoral membranes may offer a promising administration route for lipophilic peptide drugs. The aim of the present study was to investigate the effect of alpha-cyclodextrin (alpha-CD) and a novel chitosan derivative, chitosan N-betainate (CH), on sublingual absorption of a hydrophobic model peptide cyclosporin A (CsA), and the effect of temperature on the complexation of CsA with alpha-CD. Complexation of CsA with alpha-CD was studied using the phase-solubility method.

tert-Butyldimethylsilyl O-protected chitosan and chitooligosaccharides: useful precursors for N-modifications in common organic solvents.

An efficient and chemoselective procedure for preparing highly organosoluble 3,6-di-O-tert-butyldimethylsilyl (TBDMS)-chitosan and chitooligosaccharides is reported. The selective modification of the chitooligosaccharides with 0.50 degree of N-acetylation was achieved by using TBDMSCl as the reagent in combination with DMF/imidazole.

Effect of N-betainate and N-piperazine derivatives of chitosan on the paracellular transport of mannitol in Caco-2 cells.

The effects of novel quaternary chitosan derivatives on the paracellular transport of mannitol and cell viability were studied in the Caco-2 cell model. The N-betainate derivative with the degree of substitution of 0.05 was very effective at 1.

Synthesis of novel quaternary chitosan derivatives via N-Chloroacyl-6-O-triphenylmethylchitosans.

Various quaternary chitosan derivative structures were synthesized by reacting N-chloroacyl-6-O-triphenylmethylchitosans with tertiary amines. Full substitutions were obtained from the quaternization reactions and the obtained water-soluble quaternary chitosan derivatives were thoroughly characterized with (1)H NMR, (13)C NMR, (1)H-(13)C HSQC NMR, and FT-IR.

Novel water-soluble quaternary piperazine derivatives of chitosan: synthesis and characterization.

Novel synthesis methods for the preparation of quaternary piperazine derivatives of chitosan were developed. Quaternary ammonium moiety can be selectively inserted into either one or both of the piperazine nitrogens, yielding structurally uniform chitosan derivative structures. Water-soluble end products were thoroughly characterized with FT-IR, 1H NMR, 13C NMR and 2D 1H-13C HSQC NMR.

N-Chloroacyl-6-O-triphenylmethylchitosans: useful intermediates for synthetic modifications of chitosan.

An efficient synthetic route was developed for the mild chloroacylation of chitosan with different chloroacyl chlorides. Full N-chloroacylation was obtained with this procedure without any O-acylation, and products having lower degrees of substitution can also be produced. Organo-soluble 6-O-triphenylmethylchitosan was used as a starting material for the acylation reactions.