Background/Objectives: Cervical dysplasia, a precursor to cervical cancer, represents a significant global health challenge, particularly in regions like Central America, Africa, and Southeast Asia. Current management approaches rely on surgical or ablative interventions, which can lead to complications, for example, preterm birth and cervical insufficiency. Therefore, developing non-invasive, localized therapeutic alternatives is of great clinical interest. Curcumin is a natural compound that suppresses the progression of cervical cancer, but it has poor oral bioavailability and high clearance. Methods: We incorporated curcumin into solid lipid nanoparticles, which were then loaded into rapidly dissolving films. These films show the sustained release profile of curcumin at the localized vaginal site, demonstrating release kinetics consistent with the Korsmeyer–Peppas model. Results: The curcumin solid lipid nanoparticles yielded a size of 341 nm and a polydispersity index of 0.373, and the zeta potential was −23.4 mV. The encapsulation efficiency of curcumin solid lipid nanoparticles was 77.27% using a validated HPLC method. FTIR analysis supported successful incorporation of curcumin into the lipid matrix. A Box–Behnken Design of Experiments optimized the key film formulation parameters and yielded a film with a tensile strength of 2.8 mPa, disintegration time of 3 min, folding endurance of 263, film thickness of 0.426 mm and a pH of 4.0. Conclusions: In vitro assays in human cervical carcinoma cells demonstrated enhanced mortality and autophagosome formation by the curcumin solid lipid nanoparticles when compared to free curcumin. Surface expression of MHC I, MHCII, CD40 and CD80 in peripheral dendritic cells was significantly higher in the curcumin solid lipid nanoparticles than in free curcumin. Results show that solid lipid nanoparticles loaded with curcumin effectively stimulate and activate dendritic cells, supporting immune cell activation outside the tumor microenvironment. The proposed pain-free self-administration strategies will lead to increased patient compliance.

Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4⁺ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity.

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There is a need for mucosal adjuvants; hence, we explored the potential of repurposing existing drugs with established safety profiles in humans. Polymyxins are a class of clinically used antibiotics. They are cationic peptides and mast cell activators, which are a novel class of vaccination adjuvants. The goal was to assess the adjuvant properties of Polymyxin B microparticles in combination with vaccine candidates previously developed in our laboratory, such as microparticulate gonorrhea, influenza, measles, Zika, and canine coronavirus vaccines, and to compare their performance with FDA-licensed adjuvants, such as MF59 and Alum. Methods: Polymyxin microparticles were formulated using a double emulsion method, and the toxicity profile and autophagosome generation of Polymyxin B microparticles were assessed. The immunogenic potential of Polymyxin B in these vaccines was studied using multiple parameters such as nitric oxide release using Griess assay and immune profiling using flow cytometry for markers such as MHC I, MHC II, CD40, and CD80. Results: Polymyxin B microparticles were found to be non-cytotoxic to dendritic cells up to 500 μg/mL. Polymyxin B promoted autophagosome formation and nitric oxide release, and showed the upregulation of MHC I, MHC II, CD80, and CD40 pathways. Conclusions: The adjuvant activity of Polymyxin B across various vaccine platforms is significantly comparable to FDA-approved adjuvants, which is a critical requirement for generating T cell responses such as helper T cell and cytotoxic CD8+ T cell responses.

Background/Objectives: Gonorrhea remains one of the most prevalent sexually transmitted infections globally, with an estimated 82–87 million new infections annually and no licensed vaccine available. Antigenic variability and the lack of durable protective immunity following natural infection have been major obstacles to vaccine development. We previously developed an adjuvanted, formalin-inactivated whole-cell gonococcal microparticle (GC-MP) vaccine delivered by dissolving microneedles and demonstrated that it induced functional antibodies and enhanced bacterial clearance in murine models. Here, we evaluated this GC-MP microneedle platform in Rhesus macaques to provide proof-of-concept data in a relevant large-animal model and to compare different adjuvants. Methods: Rhesus macaques were allocated into five groups and vaccinated, and serum antigen-specific IgG and IgA responses were quantified by ELISA, with functional activity assessed by serum bactericidal assay. In parallel, the potency of delta-inulin-, aluminum-phosphate-, or aluminum-hydroxide-adjuvanted N. gonorrhoeae-loaded microparticles to activate dendritic cells was assessed in vitro via changes in surface expression of MHC I, MHC II, CD40, and CD80. Results: The serum from vaccinated primates demonstrated elevated gonococcal-specific IgG and IgA responses compared with naïve controls and measurable bactericidal activity against live, homologous N. gonorrhoeae strains. All adjuvanted formulations increased dendritic cell expression of MHC I, MHC II, CD40, and CD80. Conclusions: These findings indicate that an adjuvanted whole-cell inactivated gonorrhea vaccine delivered transdermally via microneedles elicits clearly elevated, relative to controls, functional antibody responses, supporting its advancement toward clinical evaluation.