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The objective of this paper is to elucidate the influence of fatty glyceride chain length in chitosan copolymers on the peroral absorption of enoxaparin. First of all, a series of chitosan copolymers with glyceryl monocaprylate (GM8), glyceryl monolaurate (GM12) and glyceryl monostearate (GM18) as the hydrophobic part were synthesized. The structure of the copolymers was characterized using proton nuclear magnetic resonance. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that all the copolymers were non-toxic. Enoxaparin nanocomplexes were prepared by self-assembly. Mucoadhesion of the nanocomplexes was characterized using the mucin particle method. Nanocomplex uptake and transport were quantified in Caco-2 cells and cellular localization was visualized by confocal laser scanning microscopy. Enoxaparin uptake was enhanced by nanocomplex formation, and was dependent on incubation time, concentration, temperature and glyceride chain length. The GM8 grafted chitosan-enoxaparin nanocomplex exhibited the strongest bioadhesion and the best uptake and transport in both cell culture and in vivo absorption in rats. The uptake mechanism was assumed to be adsorptive endocytosis via clathrin- and caveolae-mediated processes. In conclusion, oral absorption of enoxaparin can be further enhanced by using GM8 grafted chitosan copolymer as the carrier to form nanocomplexes.

To maximize the interference efficacy of pGPU6/Neo-p65 shRNA-expressing pDNA (p65 shRNA) and subsequently more effectively inhibit tumor growth and lymphatic metastasis through blocking the nuclear factor-kappa B (NF-κB) signaling pathway, seven Tween 85-polyethyleneimine (PEI) conjugates (TnPs, n=2, 3, 4, 5, 6, 7 and 8), which differed in the length of the polymethylene [-(CH2)n-] spacer between Tween 85 and PEI, were synthesized and investigated. The results showed that the transfection efficiency and cytotoxicity both increased with the spacer chain length. Then, TnPs with a [-(CH2)6-] spacer (T6P) were chosen to deliver p65 shRNA to a tumor and subsequently inhibit tumor growth and lymphatic metastasis. The T6P/p65 shRNA complex nanoparticles (T6Ns) could significantly down-regulate p65 expression in breast cancer cells, and consequently inhibit cell invasion and disrupt the tube formation. Most importantly, T6Ns accumulated greatly in tumor tissue, and as a result, significantly inhibited the growth and lymphatic metastasis of breast cancer xenograft. All these results indicated that the transfection efficacies of cationic amphiphiles could be significantly modulated by minor structural variations, and that T6P was promising for the effective delivery of p65 shRNA to knock down the expression of the key metastasis-driving genes and inhibit tumor growth and metastasis.