Study On Effects Of Chitosan Oligomers And D-Glucosamine Amides On Drugs Transdermal Delivery Properties

Transdermal drug delivery system (TDDS) attracts the attentions from the pharmaceutical industry for its advantages. However, the skin barrier limits the development of TDDS. Safe and effective transdermal enhancers were employed to overcome this barrier. To seek for novel, safe and effective transdermal enhancers, this thesis was focused on the effects of chitosan oligomers and its relative derivatives on transdermal delivery of Baicalin and Baicalein.In this dissertation, the methods of HPLC were set up to determine Baicalin and Baicalein quantitatively. Then the effects of chitosan oligomers on Baicalin and Baicalein transdermal delivery were studied in vitro. The results showed that there should be a critical value of molecular weight and concentration of chitosans and pH of solutions which could best enhanced Baicalin percutaneous delivery rate. There was no significant change on the Q24 of Baicalin when using N-acetyl-D-glucosamine as enhancer. Contrary to this, when using D-glucosamine as enhancer, the EFQ was raised to 5.3(P<0.05). Therefore, one could suggest that the effective unit of chitosans is D-glucosamine. Chitosan could enhance the transdermal delivery of baicalein and this enhancement also varied with the chitosan concentration.Meanwhile, effects of D-glucosamine amides on Baicalin and Baicalein transdermal delivery were studied using Azone and Oleic acid as control enhancers. Results indicated that all derivatives exhibited better enhancement effects than OA and among these compounds, DGS, DGP, DGD, DGC, DGH, DGO and DGFAP showed better enhancement effects than Azone. Enhancement effects of D-glucosamine amides were studied relating to the chemical structure, including the length of alkyl chain, the double bond and polar group. In the series of 2-deoxy-2-alkylamide-β-D-glucopyranose, the compound with 8 carbon atoms in the alkyl chain performed the best enhancing effect. However, the compound having 16 carbon atoms in the alkyl chain resulted in the best effect in the series of 2-deoxy-2-(4′-alkoxy-3′-methoxy cinnamoylamide)-β-D-glucopyranose. When the polar group and the length of alkyl chain remain the same, the compound with a double bond in the alkyl chain showed the better permeation enhancement factor. When the alkyl chain was the same, the compound with a glucopyranose as its polar group led to better permeation effect. However, the enhancement effect of these derivatives on Baicalein was weaker than on Baicalin, which suggested that they only...