Nunzio Denora

Chronic wound infections are difficult to treat because they involve polymicrobial communities, biofilm-associated tolerance, impaired healing and repeated antimicrobial exposure. These factors promote persistence and antimicrobial resistance, while the development of new antibacterial agents remains costly and prone to failure. This review discusses a Digital Twin framework for supporting multitarget antibacterial discovery and formulation design in chronic wound infections. The proposed concept integrates microbiological and epidemiological data, bacterial target networks, structure-based screening of plant-derived metabolites, and formulation-dependent release prediction. Natural compounds are particularly relevant because many phytochemicals affect several bacterial processes, including membrane integrity, cell wall biosynthesis, DNA-related targets, quorum sensing, and biofilm formation. However, their use is often limited by poor solubility, low stability, and insufficient local exposure. Therefore, the framework also includes delivery-system engineering, such as electrospun fibres, polymeric nanoparticles, lipid-based carriers and controlled-release platforms. Machine learning models may then be used to link formulation descriptors with predicted release profiles and local antibacterial exposure. The practical output of the framework is a prioritised set of compound–target–carrier combinations. The proposed Digital Twin framework is conceptual and has not yet been experimentally validated; however, it may reduce empirical screening and support more rational selection of such combinations for chronic wound management.

Background/Objectives: Niaprazine is widely used for the management of sleep disorders in pediatric and geriatric patients; however, no commercially available oral liquid formulation is currently available in Italy, making extemporaneous compounding necessary. In routine practice, the beyond-use date (BUD) is often limited to 30 days, potentially affecting therapeutic continuity. This study aimed to evaluate the chemical, physical, and microbiological stability of a compounded niaprazine syrup to support evidence-based BUD and to assess the suitability of selected ready-to-use compounding vehicles for preparing alternative niaprazine oral liquid formulations. Methods: A niaprazine syrup (3 mg·mL⁻¹) was prepared in a sucrose-based vehicle acidified with tartaric acid and preserved with potassium sorbate. Chemical stability of niaprazine was evaluated by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD), whose specificity was confirmed by forced degradation studies. Stability was monitored for up to 9 months at 4–8, 25, and 40 °C and confirmed after 12 months by HPLC-DAD and mass spectrometry (MS). Physical stability of the formulation was monitored by pH and visual inspection up to 12 months. Microbiological quality was assessed for 2 months at 4–8 and 25 °C according to the European Pharmacopoeia. In parallel, four selected ready-to-use compounding vehicles were evaluated for their suitability to prepare stable niaprazine oral liquid formulations. Results: Niaprazine concentrations in the syrup remained within pharmacopeial acceptance limits (±10%) at all temperatures, although a decrease was observed under accelerated conditions (40 °C). pH remained stable (≤0.5-unit variation) and the formulation stayed clear and homogeneous throughout the study, with only minor visual changes after prolonged storage at 40 °C. Statistically significant differences (p < 0.05) were observed in both the HPLC-DAD and HPLC-MS datasets. Microbiological testing confirmed compliance up to 2 months at 4–8 and 25 °C (TAMC ≤ 10³ CFU/mL; TYMC ≤ 10² CFU/mL; Escherichia coli absent). Comparable chemical and physical stability was observed for three of the four formulations prepared with the ready-to-use vehicles over at least two months. Conclusions: The compounded niaprazine syrup demonstrated chemical, physical, and microbiological stability under refrigerated and room-temperature storage, supporting evidence-based beyond-use dating of up to two months under the tested conditions. Ready-to-use vehicles may represent a practical complementary approach, offering standardized alternatives for the preparation of niaprazine oral liquid formulations.

Oral delivery of bioactive compounds in veterinary medicine offers important opportunities to improve animal health, productivity, and welfare, but its effectiveness is often limited by species-specific gastrointestinal physiology. This review aims to provide a comprehensive overview of microencapsulation strategies for oral veterinary delivery, focusing on species-specific gastrointestinal barriers and the formulation approaches developed to overcome them. Monogastric and ruminant animals present distinct gastrointestinal environments that compromise the stability, bioavailability, and therapeutic performance of orally administered compounds. In monogastrics, gastric acidity, digestive enzymes, gastrointestinal transit, and microbiota-mediated interactions represent major barriers, whereas in ruminants, ruminal fermentation, prolonged retention, and physicochemical conditions may cause premature degradation of bioactive compounds. These barriers significantly hinder the successful use of probiotics, enzymes, essential oils, nutrients, vaccines, and veterinary drugs. However, microencapsulation has emerged as a promising solution, providing a protective barrier that improves compound stability, enhances gastrointestinal survival, and enables controlled or site-specific release. By preserving bioactivity and modulating release kinetics, microencapsulation contributes to improved delivery efficiency and functional performance. A distinctive feature of this review is the integration of species-specific gastrointestinal physiology with microencapsulation technologies to provide a rational framework for designing oral delivery systems in veterinary medicine, rather than focusing solely on individual encapsulation technologies. Current challenges related to material selection, formulation optimisation, and industrial scalability are discussed. Overall, this review highlights that integrating gastrointestinal physiology with advanced microencapsulation technologies is essential for developing effective, targeted, and sustainable oral delivery systems, ultimately supporting improved animal health, productivity, and welfare.

Cold plasma (CP) has emerged as a multifunctional surface engineering technology capable of enabling precise, non-thermal modification of material interfaces, while additive manufacturing (AM) has transformed modern fabrication through a layer-by-layer model of personalized therapies. This review discusses potential interactions between cold plasma technologies and additive manufacturing processes for pharmaceutical and biomedical applications. CP has been investigated for surface modifications before and after manufacturing processes in several material science applications. Through controlled surface activation and plasma-induced chemistry, CP-assisted processes can enhance interlayer adhesion, surface wettability, antimicrobial activity, and bioactivity of AM-fabricated models, by generating reactive species and introducing functional groups into the surfaces of materials. The review also discusses engineering and regulatory challenges associated with plasma technologies in AM. Overall, CP represents a versatile surface modification technology whose interaction with materials used in AM deserves further investigation.

Chronic unresolved inflammation is a common feature of several Central Nervous System (CNS) disorders, including autism spectrum disorder (ASD). We previously demonstrated that Formyl Peptide Receptor 2 (FPR2) activation by our agonist MR-39 reduced several inflammatory markers and improved social behavior in two validated animal models of ASD. Therefore, we decided to delve deeper into the potential of MR-39 as a drug for treating ASD. We first investigated the molecular mechanisms underlying the beneficial effects of MR-39 in BTBR mice. MR-39 significantly normalized pro-inflammatory cytokine release and NF-κB expression in the hippocampus and cortex, resulting in upregulation of synaptophysin protein levels, which, in turn, promote plasticity and correct abnormalities in dendritic spine morphology. Next, we characterized the safety and pharmacokinetic profile of MR-39 with respect to potential advancement for further pre- and clinical studies. We found that MR-39 was not genotoxic and safe to use since it had limited interaction with the majority of the targets associated with the adverse drug reaction. Consistently, a repeated-dose administration study evidenced no clinical signs attributable to treatment-related toxicity. On the other hand, MR-39 exhibited rapid hepatocyte clearance and interaction with efflux systems in vitro, suggesting possible limitations due to its pharmacokinetic properties. Finally, we explored multiple strategies to overcome MR-39’s low aqueous solubility, finding that the cosolvent approach can greatly enhance solubility and wettability. Overall, our study confirmed that promoting inflammation resolution with MR-39 can open new therapeutic options for ASD and that this compound has potential as a drug.