Abstract

Spaceflight-associated bone loss poses a major health risk during long-duration missions due to microgravity, altered calcium metabolism, and increased bone resorption. Current countermeasures, including bisphosphonates and exercise, are only partially effective. This seminar explores the concept of biomarker-guided nanopharmaceutics, where bone turnover biomarkers such as C-terminal telopeptide (CTX), alkaline phosphatase (ALP), or osteocalcin serve as triggers for localized and controlled drug release. Smart nano carriers engineered with stimuli-responsive chemistries can deliver anti-resorptive or anabolic agents directly to bone tissue, improving efficacy and reducing systemic side effects. This approach integrates chemistry, pharmaceutics, and nanomedicine to address a critical challenge in space healthcare.

Introduction

Astronauts lose ~1–2% of bone mass per month in microgravity. Traditional pharmacological interventions require frequent dosing and risk systemic toxicity. Biomarker-based pharmaceutics provide precision by linking drug release to biological signals of bone remodeling.

Aim: To design smart nanomedicines guided by bone turnover biomarkers for targeted, on-demand therapy.

Methods

Biomarker Identification: Monitor CTX, ALP, osteocalcin as indicators of resorption/formation. Nanocarrier Design: Polymeric/lipid nanoparticles functionalized with bone-targeting ligands (e.g., bisphosphonate moieties).Stimuli-Responsiveness: Incorporation of redox- or enzyme-sensitive linkers activated by elevated biomarker levels. Validation: In vitro: Bone cell culture under simulated microgravity. In vivo: Rodent models exposed to hindlimb unloading.

Results

Targeted release of antiresorptives at high CTX levels. Enhanced bone density preservation with lower systemic drug exposure. Adaptive, personalized dosing guided by biomarker fluctuations.

Conclusion

Biomarker-guided nano pharmaceutics represent an innovative pharmaceutical strategy for preventing bone loss in space. By merging biomarker science with smart nano medicine, this approach promises safer, more effective, and adaptive therapies—essential not only for astronauts but also for osteoporosis management on Earth.

Introduction

Eye infections present major challenges for treatment, due to the microbial species and the low ocular bioavailability of drug. A fortified eye drop is, in some case, the only option for administering antibiotics such as Cefazolin. It is an extemporaneous preparation with limit stability and needs to be injected via the painful intraocular route. In order to improve ocular tolerance and the efficacy of Cefazolin, we developed a colloidal eye drop containing lipid microparticles loaded with this drug which can be administrable by instillation.

Methods

Cefazolin lipid microparticles were prepared by high shear homogenization method using an Ultraturrax at 20,000 rpm for 5 minutes. The lipid matrix was composed of carnauba wax and a pair of surfactants. The particle size was evaluated by optical microscopy, while encapsulation efficiency was performed by spectrophotometry at 272nm in water. The in vitro release study was conducted in dialysis bag immersed in artificial tear fluid. Microbiological efficacy was assessed on sensitive strains of Pseudomonas aeruginosa and Escherichia coli. Ocular tolerability was assessed by a HET CAM test on embryonated test.

Results

The lipid microparticles exhibited a monodisperse distribution with a mean diameter of 1.1 µm. The recorded encapsulation efficiency was 87% and the antimicrobial activity was satisfactory. The in vitro release of the colloidal eye drop demonstrated enhanced diffusion and a delayed release profile, with a Cmax shift of 50 minutes compared to the aqueous solution of cefazolin. The pH and osmolarity were favorable for ocular administration. The HETCAM results didn’t show any sign of irritation at 5 min.

Conclusion

The colloidal eye drop of lipid microparticles encapsulating Cefazolin represents a promising advance in the treatment of eye infections, aiming to enhance intraocular permeability and prolong the action of the antibiotic.

The antimicrobial properties of silver(I) ions have been recognized since ancient times. In recent decades, silver(I) complexes have been extensively studied for their antimicrobial activity. The ligand plays a crucial role not only in stabilizing the complex but also in modulating its physicochemical properties, such as solubility, lipophilicity, and the ability to release silver(I) ions under biological conditions. In addition to their broad spectrum of applications, silver(I) complexes are noted for their low toxicity to human cells and the remarkably low tendency of microorganisms to develop resistance. These characteristics make silver(I) complexes promising candidates for the development of novel antimicrobial agents, particularly in the fight against bacterial resistance to clinically used antibiotics. The possible mechanism of the antimicrobial activity of silver(I) complexes can be attributed to their interactions with biological molecules, including DNA and proteins. Thiabendazole is a benzimidazole derivative widely used as a pesticide, known for its potent antifungal and anthelmintic activities. Due to its favorable pharmacological profile, thiabendazole has attracted attention as a structural scaffold for the development of metal complexes with potential biological activity. In this study, we employed a benzyl-substituted derivative of thiabendazole, N-benzylthiabendazole (N-BzTBZ), as a ligand to synthesize a novel mononuclear silver(I) complex, [Ag(N-BzTBZ)₂]CF₃SO₃, exhibiting a distorted trigonal planar geometry. The binding affinity of both the free ligand and the synthesized complex with biologically relevant targets, bovine serum albumin (BSA) and calf thymus DNA (ct-DNA), were investigated using fluorescence emission spectroscopy.

Nitrogen-containing aromatic heterocycles have garnered significant interest as essential scaffolds in the synthesis of bioactive compounds, owing to their broad applications in various pharmacological fields, including vitamins, herbicides, antifungal, antibacterial, and anticancer agents. Their unique structural and electronic properties allow them to interact effectively with biological targets, making them attractive ligands in the design of metal-based therapeutic agents. In the present study, azaconazole (acz) was employed for the synthesis of a mononuclear gold(III) complex, [AuCl₃(acz)]. The complex was obtained by reacting equimolar amounts of potassium tetrachloridoaurate(III) and the acz ligand under reflux conditions for 3 h. In this complex, azaconazole coordinates monodentately to the Au(III) ion, while the remaining coordination sites in the square-planar geometry are occupied by chloride ions. The interaction between the synthesized gold(III) complex and calf thymus DNA (ct-DNA) was investigated using fluorescence emission spectroscopy in the presence of the intercalative agent ethidium bromide (EthBr) and the minor groove binder Hoechst 33258 (Hoe). Additionally, fluorescence competition experiments were performed using specific site markers, including eosin Y, ibuprofen, and digitoxin, to gain deeper insight into the binding sites on BSA. Eosin Y is known as a marker for site I (subdomain IIA), ibuprofen for site II (subdomain IIIA), and digitoxin for site III (subdomain IB).

Gallium(III) complexes have emerged as promising candidates in bioinorganic chemistry due to their structural versatility, stability, and ability to mimic iron in biological systems, which allows them to interact selectively with key biomolecules. Motivated by these properties, we synthesized two novel gallium(III) complexes, Na[Ga(ida)₂]·2H₂O (1) and K[Ga(ida)₂]·3H₂O (2), employing iminodiacetate (ida^2–) as the ligand. The synthesis of these complexes was carried out in aqueous solution by reacting GaCl₃ with iminodiacetic acid (H₂ida) at 80 °C for 4 h in the presence of NaOH or KOH, respectively. Their structures were determined using IR and NMR (¹H and ¹³C) spectroscopy and further confirmed through single-crystal X-ray diffraction analysis. Building on this structural work, we investigated their interactions with bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) using fluorescence emission spectroscopy to assess their binding affinity towards these biologically important molecules. Since serum albumin consists of three main domains (I–III), each subdivided into two subdomains (A and B), fluorescence competition experiments with site-specific markers were also performed to identify the preferred binding sites of the complexes. Eosin Y served as a marker for site I (subdomain IIA), ibuprofen for site II (subdomain IIIA), and digitoxin for site III (subdomain IB).

The growing spread of NDM-1–producing bacteria represents a critical threat to the clinical efficacy of β-lactam antibiotics, including carbapenems, which are considered last-resort drugs. The continuous emergence of resistant strains underscores the urgent need to identify novel inhibitors capable of restoring the effectiveness of these antibiotics. In this study, a comprehensive computational protocol was applied to evaluate the inhibitory potential of four candidate compounds (M1, M2, P3, and P4) against the metallo-β-lactamase NDM-1. The workflow included 100 ns molecular dynamics simulations to explore the conformational stability of each complex, complemented by structural stability analyses (RMSD, RMSF), residue–ligand distance monitoring, and assessment of hydrogen bond evolution. Binding free energy calculations using the MM/GBSA approach were further conducted to provide thermodynamic insights into ligand affinity and complex stability.

The results demonstrated that compounds M2 and P4 exhibited superior dynamic behavior, maintaining stronger and more persistent interactions with catalytically relevant residues of the enzyme. These findings were reinforced by more favorable mean ΔG_bind values (–13.56 and –16.72 kcal/mol, respectively), suggesting robust binding affinity. Additionally, structural superimpositions over simulation time revealed distinct adaptive capacities of the ligands to the catalytic pocket, highlighting potential differences in their inhibitory mechanisms. Overall, the study positions M2 and P4 as promising scaffolds for the rational development of next-generation NDM-1 inhibitors. Moreover, the findings validate the utility of multivariate in silico approaches that integrate molecular dynamics, free energy calculations, and interaction mapping as powerful tools to prioritize candidates for experimental testing, ultimately supporting innovative strategies to counteract bacterial resistance.

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Introduction: Parkinson's disease (PD) is a neurodegenerative disorder that to date remains incurable. PD is currently linked to chronic sleep restriction (SR) as these pathologies share a similar spectrum of molecular and cellular malfunctions: accumulation of aberrant proteins, neurodegeneration, neuroinflammation, activation of unfolded protein response (UPR) apoptotic branch. Development of neuroprotective strategies for PD and SR-associated neurodegeneration remains a critical issue for pharmaceutics. Prospective drug candidates should possess high bioavailability for the brain, and the ability to influence main pathogenetic mechanisms of neurodegeneration. One of the promising drug molecules is the GRP78 (HSPA5). The objective of this study was to evaluate the protective potential of recombinant GRP78 (rGRP78) administered intranasally in a PD and SR rodent models.

Methods: The work was carried out on male Wistar rats (6 months). Microinjections of the proteasome inhibitor lactacystin (LC) into substantia nigra (SN) were used to create a PD model. SR was carried out in a polyphase manner for 5 days using a swinging platform. rGRP78 was administered intranasally 4 and 24 hours after each LC microinjection and every day during SR. Control group received LC and/or GRP78 solvents. Pathomorphological and neurochemical changes were assessed by immunohistochemistry and by Western Blot. Confocal microscopy was used to assess rGRP78 bioavailability. Statistical analysis was conducted via two-factor ANOVA and Tukey post-hoc.

Results: It was proven that SR and PD share common molecular and cellular pathological mechanisms involved in neurodegeneration. It was established that intranasally administered rGRP78 is internalized by neurons and microglia in various brain structures. rGRP78 prevents development of neurodegeneration in PD and SR due to its ability to counteract (1) aS pathology; (2) apoptotic UPR branch activation; (3) microgliosis and NF-kB-induced proinflammatory changes.

Conclusion: rGRP78 is a bioavailable to the brain tissue drug that possesses a complex protective effect in neurodegenerative pathologies.

Myocardial ischemia/reperfusion injury (MI/RI) remains a major challenge in the treatment of acute myocardial infarction due to the lack of effective therapeutic options. Despite advancements in interventional techniques like percutaneous coronary intervention, MI/RI-induced oxidative stress, inflammatory responses, and cardiomyocyte apoptosis still lead to poor long-term prognosis for patients. While mesenchymal stromal cells (MSCs) and their derivates show promising potential for MI/RI therapy, their clinical application is hindered by low transplantation efficiency—often resulting from poor cell retention in the ischemic myocardium—and insufficient yield for large-scale clinical use. In this study, we engineered nanoscale artificial cell-derived vesicles (ACDVs) by extruding Ginsenoside Rg1-primed MSCs (Rg1-MSCs), resulting in Rg1-ACDVs. Rg1-ACDVs displayed superior therapeutic efficacy compared to non-primed ACDVs and extracellular vesicles derived from Rg1-MSCs (Rg1-EVs), as evidenced by reduced myocardial infarct size in rat MI/RI models. Multi-omics analysis revealed that Rg1-ACDVs possess distinct molecular signatures associated with promoting cell cycle progression and reducing DNA damage, including upregulated expression of DNA repair-related proteins and cell cycle regulators. These findings were further validated experimentally, demonstrating that Rg1-ACDVs effectively reduce reactive oxygen species (ROS) accumulation—an important driver of MI/RI—and mitigate DNA damage both in vitro (in cultured cardiomyocytes) and in vivo (in rat MI/RI models). This study highlights the synergistic benefits of combining Ginsenoside Rg1 priming (which modulates MSC paracrine function) with nanoscale engineering (which optimizes vesicle delivery), and introduces Rg1-ACDVs as a scalable and innovative strategy, offering a promising approach for improving clinical outcomes in MI/RI therapy.

Nanotechnology has emerged as an innovative tool capable of overcoming the limitations of traditional drug delivery systems by enabling the manipulation of materials at the nanometric scale, giving them unique properties such as enhanced solubility, increased stability, and drug targeting to the therapeutic site of action. Among the most significant advantages that nanosystems have, is the fact that they allow the co-encapsulation of multiple drugs within a single nanosystem, harnessing their synergistic effects, contributing significantly to the reduction of potential side effects associated with conventional multiple therapy and with a potential impact on patient compliance. This literature review explores studies analyzing the potential of simultaneous delivery of three drugs within different types of nanosystems, for the treatment of chronic and infectious diseases, namely rheumatoid arthritis, psoriasis, human immunodeficiency virus infection, Helicobacter pylori infection, and anti-inflammatory therapies, as well as conditions such as secondary degeneration following neurotrauma, being the first of its kind, and filling an existing gap in the scientific literature. Parameters such as particle size, polydispersity index, zeta potential, encapsulation efficiency, and in vitro and in vivo efficacy and safety assays consistently demonstrated efficient co-encapsulation of multiple drugs with potential pharmacological synergy, controlled and prolonged drug release, and the capacity for therapeutic site-specific targeting, thereby increasing bioavailability and enabling the reduction of systemic adverse effects. While transition into clinical practice still faces regulatory hurdles, and in-depth long-term safety assessments are needed, overall nanosystems could play a leading role in the future of nanomedicine towards more effective and personalized therapies.

This study explores the preparation and characterization of soy lecithin vesicles modified with dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHO), focusing on how these compositional changes modulate bilayer fluidity and permeability. Large unilamellar vesicles (LUVs) with narrow size distribution were successfully obtained by the extrusion method, and unencapsulated ferricyanide was efficiently removed by gel chromatography on Sephadex. Remarkably, the incorporation of saturated DPPC enabled the formation of stable LUVs at room temperature, well below its gel-to-liquid crystalline phase transition temperature (~41 °C), a challenging task when using DPPC alone.

Bilayer fluidity was assessed using the fluorescent probe 6-propionyl-2-(N’,N’-dimethyl) aminonaphthalene (PRODAN), while permeability was evaluated through the encapsulation and release of Kâ‚„[Fe(CN)₆], a hydrophilic and electroactive molecule. Incorporation of the analyte did not affect vesicle assembly.

The highest bilayer fluidity was observed in Lec:Cho (1:1.6) and Lec:DPPC (1:2) systems, whereas Lec:DOPC mixtures were dominated by the ordering effect of DOPC.

Release studies revealed striking formulation-dependent differences. Complete release of K₄[Fe(CN)₆] occurred in Lec:Cho (1:1.6), Lec:DPPC (1:2), and Lec:DOPC (1:1), while lecithin, Lec:DOPC (1:2), and pure DOPC vesicles showed partial release of 63%, 59%, and 22%, respectively. Notably, release rates were not directly correlated with release percentages: lecithin vesicles exhibited the fastest release (0.79%/min), whereas Lec:DOPC (1:1) vesicles were the slowest (0.19%/min). Overall, these results establish a clear correlation between bilayer fluidity and the release rate of ionic hydrophilic molecules, while also demonstrating that compositional tuning, particularly with DPPC, allows the design of lecithin-based nanocarriers with tailored permeability. This approach opens new opportunities for the development of vesicle-based delivery systems in nanomedicine using ionic analytes.