RESUMO
N,N,N-Trimethyl chitosan (TMC) is a quaternized chitosan with versatile biological features. However, low mechanical strength limits its uses, for example, as hydrogels for tissue engineering applications. This study illustrates a viable synthesis of metal/polymer hybrid, core-shell colloidal particles and their use as reinforcing and antioxidant fillers for TMC hydrogels. The core-shell particles were initially synthesized by surfactant-free emulsion polymerization, induced by a photo-redox initiating system of riboflavin assisted by a 3° amine and 2° alcohol co-initiators. The synthesized core-shell particles were based on two polymeric shells: TMC and chitosan, and two polymeric cores: poly (hydroxypropyl methacrylate) (PHPMA) and poly(2-hydroxy ethyl methacrylate) (PHEMA). The presence of both 3° amine on TMC and 2° alcohol on HPMA monomer enhanced the photopolymerization performance. The TMC-based particles had sizes of 122-154 nm and zeta potentials of 10-35 mV, bringing the colloidal stability in the 4-10 pH range. Furthermore, due to the presence of TMC on the shell layer, the core-shell particles could be used as templates to grow the Ag/Au bimetallic nanoparticles with alloy and core-shell types through a thermal reduction. The prepared hybrid particles were incorporated in TMC hydrogels as a multifunctional filler, improving their mechanical and antioxidant properties.
RESUMO
The uneven immunogenicity of the attenuated tetravalent dengue vaccine has made it difficult to achieve balanced protection against all four serotypes of the dengue virus (DENV). To overcome this problem, non-replicative vaccines have come into focus, as their immunogenicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composed of UV-inactivated dengue virus-2 (UV-DENV-2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by BCG-CWS significantly augmenting antibody-mediated complement-fixing activity, strongly stimulating the antigen-specific polyfunctional T cell responses, and activating mixed Th-1/Th-2 responses specific to DENV-2- and NS1-279 antigens. In conclusion, BCG-CWS potently adjuvanted the inactivated DENV-2 and DENV subunit immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development.
RESUMO
We report the green synthesis of trimethyl chitosan-functionalized poly(2-hydroxyethyl methacrylate) (PHEMA-TMC) nanogels via surfactant-free emulsion photopolymerization. TMC, a quaternized derivative of chitosan, was synthesized through methylation of chitosan, resulting in quaternary and tertiary amine groups as the main substitution products. TMC tertiary amine moiety and riboflavin (RF) acted as a redox photo-initiating system to generate free radicals for the polymerization under light irradiation. The effects of polymerization parameters such as irradiation time, concentrations of TMC and RF were investigated using MBA as crosslinker. Under the optimal condition of 1 % TMC, 4 % HEMA, 0.8 µM RF, 5 % MBA, and 4 h of polymerization time, the cationic PHEMA-TMC nanogel was synthesized with 76 % monomer conversion and an average diameter of about 106 nm. Moreover, the disulfide-crosslinked PHEMA-TMC nanogel was also synthesized using the disulfide dimethacrylate crosslinker, which exhibited a redox-induced degradation and release of encapsulated melatonin, potentially useful as a redox-responsive drug delivery carrier.
