Biodegradable Cationic Polycarbonates as Vaccine Adjuvants.

In this study, biodegradable cationic polycarbonate and polylactide block copolymers were synthesized and successfully used as novel vaccine adjuvants to provide enhanced anticancer immunity. The polymers formed nanoparticles with the model vaccine, ovalbumin (OVA), and the immunostimulant toll-like receptor 3 agonist poly(I:C) (a synthetic analog of the double-stranded RNA). Higher uptake of poly(I:C) by the bone marrow-derived dendritic cells and macrophages and OVA by dendritic cells was observed when delivered using the polymer adjuvant. In vivo experiments showed that these nanoparticles remained longer in the subcutaneous injection site as compared to OVA alone and led to higher production of anti-OVA specific antibodies with prolonged immunostimulation. When OVA was combined with poly(I:C) that was either co-entrapped in the same particles or as separate particles, a comparable level of anti-OVA IgG1 antibodies and interleukin-6 (IL-6) was produced in mouse blood plasma, and a similar level of cytotoxic T lymphocyte (CTL) response in mice was stimulated as compared to OVA/Alum particles. Furthermore, tumor rejection in the mice that were vaccinated for 9 months with the formulations containing the polymer adjuvant was stronger than the other treatment groups without the polymer. Notably, the cationic polycarbonates were not associated with any adverse in vivo effects. Thus, these biodegradable polymers may be promising substitutes for aluminum-based adjuvants in vaccine formulations.

Subcutaneous vaccination using injectable biodegradable hydrogels for long-term immune response.

Prolonged vaccine release enables gradual immunostimulation, providing long-term immunity. Herein, Vitamin E-PEG-Vitamin E triblock 'ABA' hydrogel, which is formed through physical cross-linking of flower-shaped micelles and can reside in vivo for >17 weeks, was employed for delivery of cancer preventive vaccines to provide sustained anticancer immunity. Mice vaccinated with hydrogel formulations produced a significantly higher quantity of antibodies compared to solution formulations. OVA was used to study EG.7-OVA tumor rejection in vaccinated mice. Among all formulations, OVA-loaded hydrogel containing aluminum-based adjuvant had the best therapeutic outcome, and only 2/10 mice developed solid tumors with significantly smaller tumor size. Moreover, no adverse effect on liver and kidney was detected with the hydrogel formulation. In a lymphoma metastasis mouse model, vaccination with the OVA-loaded hydrogel and adjuvant resulted in increased survival (66.7%) compared to other formulations (12.5-50%) over 100 days. This hydrogel is a promising formulation for sustained delivery of vaccines.

Co-delivery of antiviral and antifungal therapeutics for the treatment of sexually transmitted infections using a moldable, supramolecular hydrogel.

In this investigation, a therapeutic co-delivery hydrogel system is developed to provide effective HIV prophylaxis, alongside the prevention and/or treatment of candidiasis. Two components-a HIV reverse transcriptase inhibitor, tenofovir, and a cationic macromolecular antifungal agent derived from a vitamin D-functionalized polycarbonate (VD/BnCl (1:30))-are formulated into biodegradable vitamin D-functionalized polycarbonate/PEG-based supramolecular hydrogels. The hydrogels exhibit thixotropic properties and can be easily spread across surfaces for efficient drug absorption. Sustained release of tenofovir from the hydrogel is observed, where approximately 85% tenofovir is released within 3 h. VD/BnCl (1:30) does not impede drug diffusion from the hydrogel as the drug release profiles are similar with and without the polycation. Antimicrobial efficacy studies indicate that the hydrogels kill C. albicans efficiently with a minimum bactericidal concentration (MBC) of 0.25-0.5 g L(-1) . These hydrogels also eradicate C. albicans biofilm effectively at 4× MBC. When human dermal fibroblasts (as model mammalian cells) are treated with these hydrogels, cell viability remains high at above 80%, demonstrating excellent biocompatibility. When applied topically, this dual-functional hydrogel can potentially prevent HIV transmission and eliminate microbes that cause infections in the vulvovagina region.