Use of N-trimethyl chitosan for intranasal delivery of DNA encoding M2e-HSP70c in mice

Influenza outbreak has become a great lifethreatening disease in the world. Nasal vaccines can induce systemic IgG and mucosal IgA antibody responses, which establish two layers of immune defense against the infectious pathogens like influenza. Mucosal vaccines must overcome several limitations, including the mucociliary clearance and inefficient uptake of soluble antigens. Therefore, nasal vaccines require potent adjuvants and delivery systems. In this study we evaluated the effect of N-trimethyl chitosan [TMC] as a potent vehicle for DNA encoding M2e/HSP70c in order for intranasal administration in mice. Ectodomain of the conserved influenza matrix protein 2 [M2e], which has been found to induce heterosubtypic immunity, was fused to HSP70359-610 or C-terminus of Mycobacterium tuberculosis HSP70 [HSP70c] in pcDNA3.1 vector [pcDNA/M2e-HSP70c] and then encapsulated into a derivative of chitosan, N-trimethyl chitosan [TMC]. After encapsulation of the plasmid, physical properties of the particles were investigated using Zetasizer[R] 3000 the particles were then administered through the intranasal delivery in BALB/c mice. It was found that the particles had a size ranging between 90-120nm and positive surface charge. The intranasal immunization with M2e-HSP70c+TMC in BALB/c mice significantly induced higher M2e specific IgG than those induced in control groups [pcDNA/M2e-HSP70c without TMC, pcDNA/M2e, bearing M2e alone, and PBS]. The present study showed that the encapsulation of M2e/ HSP70c into N-trimethyl chitosan [TMC] could strongly induce the humoral immune response against the M2e-HSP70c plasmid without lowering the adjuvant efficacy of HSP70c

[Biochemical mechanism of inflammation in colorectal cancer]

Biological and chemical stimulators cause tissue injury. Many epidemiological studies imply that chronic stimulation of tissues leads to cancer. One of the most important type of chronic tissue stimulation criteria is increased activity of the metabolic pathway of arachidonic acid and production of biochemical intermediates. Cyclooxygenase pathway [COX] of arachidonic acid leads to production of a variety of prostaglandins and thromboxanes. These inflammatory agents exert their biological effects on different organs and initiate human cancers. Lately, a variety of synthetic and natural drugs have been discovered that suppress the production of these inflammatory agents and inhibit cancer promotion. One of the most popular drugs, are nonsteroidal anti-inflammatory drugs, [NSAIDs]. In this review, we discuss the role of these inflammatory agents in colorectal carcinogenesis and also their mechanism of inhibition