Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest P_app (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a leading cause of death from a single infectious agent worldwide. Conventional antibiotic therapies face significant limitations, including multidrug resistance, poor treatment adherence, limited penetration into granulomas, and systemic toxicity. Recent advances in nanomedicine have paved the way for nanotheranostic approaches that integrate therapeutic, diagnostic, and preventive functions into a single platform. Nanotheranostic systems enable targeted drug delivery to infected macrophages and granulomatous lesions, real-time imaging for disease monitoring, and controlled, stimuli-responsive release of antitubercular agents. These platforms can be engineered to modulate host immune responses through host-directed therapies (HDTs), including the induction of autophagy, regulation of apoptosis, and macrophage polarization toward the bactericidal M1 phenotype. Additionally, nanocarriers can co-deliver antibiotics, immunomodulators, or photosensitizers to enhance intracellular bacterial clearance while minimizing off-target toxicity. The review also discusses the potential of nanotechnology to improve TB prevention by enhancing vaccine efficacy, stability, and targeted delivery of immunogens such as BCG and novel subunit vaccines. Key nanoplatforms, including polymeric, lipid-based, metallic, and hybrid nanoparticles, are highlighted, along with design principles for optimizing biocompatibility, multifunctionality, and clinical translatability. Collectively, nanotheranostic strategies represent a transformative approach to TB management, bridging diagnosis, therapy, and prevention in a single, adaptable platform to address the unmet needs of this global health challenge.

Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.

Cutaneous wound healing is a complex biological process often impaired by bacterial infections, especially by Staphylococcus aureus. To address this, alginate (ALG)/chitosan (CS) polyelectrolyte multilayer (PEM) films incorporating alginate-coated silver nanoparticles (ALG–AgNPs) were fabricated by layer-by-layer self-assembly. The films exhibited a porous, layered morphology with homogeneous distribution of ALG–AgNPs, hydrophilic surfaces (contact angle ≈ 55°), a high swelling degree (~175%), and a water vapor transmission rate of 1830 g m⁻²·day⁻¹. Thermal analyses showed similar degradation profiles up to 600 °C, with the ALG–AgNP film displaying lower moisture loss and higher dehydration temperature, consistent with enhanced ionic and coordination crosslinking (–NH₃⁺/–COO⁻ and Ag–O–C bonds). The release of Ag⁺ in PBS (pH 7.4) was ~3% after 24 h, following a Korsmeyer–Peppas mechanism (R² = 0.97, n < 0.5), and degradation, with ~40% mass loss in 6 days, indicated gradual matrix disintegration. Cytocompatibility studies revealed >80% viability for fibroblasts, keratinocytes, macrophages, and 2-log reduction in adhesion, and an 11 ± 1 mm inhibition zone for S. aureus. These results demonstrate that ALG/CS–AgNP PEM films combine biocompatibility, antibacterial efficacy, controlled degradation, and structural stability, making them promising multifunctional scaffolds for the regeneration of infected skin wounds.

Cannabidiol (CBD), the main non-intoxicating phytocannabinoid of Cannabis sativa, is highly lipophilic and poorly water-soluble. We developed chitosan-coated lipid nanocapsules (NCs) loaded with a CBD-rich Cannabis sativa ethanolic extract (CEE), using medium-chain triglyceride (MCT) oil or olive oil as the lipid core and optimizing them with a Box–Behnken design; oil and Tween^® 80 volumes mainly determined hydrodynamic diameter and polydispersity. The optimized MCT oil and olive oil NCs had hydrodynamic diameters of 206.9 and 231.2 nm, PDI values of 0.130 and 0.196, zeta potentials of about +31 and +33 mV, and CBD encapsulation efficiencies above 85%. ATR-FTIR suggested different lipid organization and CBD environments in each core, while confocal microscopy located the CBD-reactive signal in the oil phase without resolving the core from the interface. MCT oil NCs retained more CBD at room temperature, but differences under other conditions were small, and the extract dissolved in the same oils behaved similarly, indicating a major contribution of the oil vehicle. Both NCs retained CBD between pH 5.5 and 7.4 and could be redispersed after freeze-drying. In a preliminary chikungunya virus assay, CEE-loaded NCs inhibited the cytopathic effect by 34–45% at non-cytotoxic concentrations, but free CEE in oil was at least as active.