These data highlight that there is still controversy with the mechanism of action of polymeric micro- and nanoparticles. PLGA micro- and nanospheres can be used for systemic or mucosal immunization [84–86]. PLGA-based systems are able to be phagocytosed by DCs, even by the oral route [87] and enhance their immunostimulatory capacity [88], leading to the upregulation of maturation markers CD40 and CD80 and release of IL-6. It has been shown that Hp91 synthetic peptide (a peptide that can induce

potent antigen-specific cytotoxic T-lymphocyte responses), both encapsulated or conjugated to the surface of PLGA nanoparticles, is able to activate both human and mouse DCs more potently than the free peptide [88]. Inhibitors,research,lifescience,medical PLGA microspheres

have been extensively studied by our research group. Different synthetic peptides have been entrapped into these microspheres, such as malarial SPf66, and have been administered by subcutaneous, intradermal [89], oral [17], or nasal [90] routes in mice. Microencapsulated SPf66 induced Inhibitors,research,lifescience,medical a superior immune response than the one obtained with the administration of the peptide adjuvanted Inhibitors,research,lifescience,medical with alum and comparable with the response obtained with FCA. In addition, these particles have been administered to Aoutus monkeys leading to high antibody levels and protection against P. falciparum challenge [91]. To our knowledge, only one clinical trial has been carried out using PLGA and synthetic peptides [92]. This phase I study evaluated the safety and immunogenicity of a synthetic HIV peptide (HIV-1 MN V3) administered intramuscularly with alum and a similar product encapsulated into PLGA microspheres administered by the oral route. However, the oral administration of this Inhibitors,research,lifescience,medical vaccine did not trigger significant humoral, cellular, or mucosal immune responses. 2.4. Liposomes Liposomes are synthetic spheres comprised by phospholipid bilayers (Figure 4). According to their structure and size, liposomes can be classified into multilamellar vesicles Inhibitors,research,lifescience,medical (MLV), small unilamellar vesicles (SUV), intermediate unilamellar vesicles (IUV), or large unilamellar vesicles (LUV) [93]. For vaccine delivery, antigens

can be encapsulated into the aqueous core, http://www.selleckchem.com/products/pifithrin-alpha.html integrated in the lipid bilayer or adsorbed on the surface [4]. Figure 4 Scheme of liposomes structure. Antigens are differently incorporated based on their nature. Hydrophilic antigens can be encapsulated into the aqueous core; amphipathic antigens and are integrated into the phospholipid bilayer, and lipidic antigens are adsorbed … The mechanism of action of liposomes is not well defined. Passive targeting, derived of their particulate nature, and tendency to interact with macrophages is likely to be an important factor, particularly for nontargeted liposomes [94]. Among the different lipids available, cationic ones have a better ability to initiate and potentiate the immune response.