Background/Objectives: Liposomes and niosomes are established drug delivery systems, some of which have received FDA approval and demonstrated therapeutic efficacy. This study investigates a novel niosome formulation, utilizing two natural food-derived components, as a cost-effective alternative to traditional nanocarriers. The active pharmaceutical ingredient, calcium fructoborate (CF), possesses notable anti-inflammatory properties. The study aims to evaluate the efficacy of this novel natural niosome (NN) system, in comparison to existing nanocarrier formulations, in an ischemia–reperfusion (I/R) pain model. Methods: An acute ischemia/reperfusion injury model was employed to induce pain in 36 rats. The efficacy of the following treatments was assessed: standard CF, liposomal CF, niosomal CF, and natural niosomal CF. Efficacy was determined by quantifying the treatments’ ability to mitigate inflammation and oxidative stress in the kidneys, lungs, heart, and liver, and by evaluating potential organ damage through histopathological analysis. Results: The NN treatment significantly reduced malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in the kidneys and liver compared to the other treatments (p < 0.05). In the kidney, NN treatment also significantly decreased creatinine levels relative to the other treatments (p < 0.01). The histopathological analysis of kidney tissue revealed that NN treatment attenuated tubular dilation, interstitial inflammation, and epithelial thinning. In the heart, liposomal treatment significantly increased MDA levels (p < 0.05) and decreased sialic acid levels (p < 0.05); however, no significant differences were observed in troponin levels (p > 0.05). In the lung, no significant differences in MDA, lactate, TNF-α, or sialic acid levels were detected among the treatment groups (p > 0.05). Conclusions: The natural niosome drug delivery system demonstrates potential as a therapeutic intervention for protecting and improving kidney and liver health. While liposomal treatment exhibited some adverse effects, it effectively suppressed inflammation. This study provides a foundation for future research and positions the NN drug delivery system as a promising, cost-effective alternative for inflammation-associated pathologies.

Background/Objectives: Extracellular Vesicles (EVs) have shown great promise as diagnostic and therapeutic tools, as well as pharmacological nanocarriers. Various strategies are being explored to develop EVs for monitoring, imaging, loading with pharmacological agents, and surface decoration with tissue-specific ligands. EVs derived from Mesenchymal Stromal Cells (MSC-EVs) are of particular interest both as therapeutics per se and as natural nanocarriers for the targeted delivery of biotherapeutics. Methods: In this study, we investigated the ability of different tags to deliver a reporter protein into canine MSC-EVs with the aim of identifying the most effective endogenous loading mechanism. To this aim, canine MSCs were engineered to express the Green Fluorescent Protein (GFP) fused to CD63, Syntenin-1, TSG101, and the palmitoylation signal of Lck, which were expected to promote GFP incorporation into EVs. Overexpression of tagged GFP in canine MSCs was confirmed by Western blotting and examined by confocal microscopy and transmission electron microscopy to map intracellular localization. Results: All tags were able to deliver GFP into EVs. Syntenin-1 showed relatively high loading efficiency and secretion index but exhibited a diffuse localization pattern in the transfected cells. The palmitoylation signal showed low loading efficiency and localization specificity. TSG101 displayed a morphological pattern consistent with specific localization in endosomal structures, but its low expression level prevented further evaluations. Finally, CD63 showed the highest expression efficiency, as GFP-CD63 levels were approximately 5-fold higher than untagged GFP. Conclusions: In conclusion, CD63 emerged as the most suitable tag for canine MSC-EV engineering. Indeed, even if the secretion index favours Syntenin-1, CD63’s higher abundance in the lysate suggests its substantial post-secretion uptake. Further studies aimed at elucidating CD63’s specific contribution and identifying the domains involved in vesicle trafficking could provide valuable insights into EV bioengineering.

Background: This study evaluates the impact of fibrinogen enrichment on the structural, mechanical, and bioactive properties of fibrin scaffold derived from balanced protein-concentrate plasma (BPCP), an autologous platelet-rich plasma (PRP) formulation with elevated extraplatelet content. Methods: A novel high-fibrinogen BPCP (HF-BPCP) scaffold was produced by combining BPCP platelet lysate with a concentrated fibrinogen solution at a 1:1 ratio, yielding nearly four-fold physiological fibrinogen levels. Comparative analyses between HF-BPCP and standard BPCP included platelet and fibrinogen quantification, scanning electron microscopy (SEM), rheology, indentation, adhesion testing, coagulation kinetics, retraction assays, biodegradation profiling, and growth factor (GF) release kinetics. Results: HF-BPCP displayed significantly denser fibrin networks with thinner fibers, higher porosity, and markedly faster coagulation times compared to BPCP. Mechanically, HF-BPCP exhibited greater stiffness, higher energy dissipation, and more stable adhesion, while almost eliminating scaffold retraction at 24 h. Despite improved early handling and structural integrity, HF-BPCP degraded more rapidly in vitro under tissue plasminogen activator exposure. GF release analysis showed reduced early peaks of platelet-derived factors (TGF-β1, PDGF-AB, VEGF) but sustained release thereafter, while extraplatelet factors (IGF-1, HGF) exhibited similar profiles between scaffolds. Conclusions: These results indicate that fibrinogen enrichment synergizes with the elevated extraplatelet protein profile of BPCP to enhance scaffold mechanical stability, handling properties, and controlled GF delivery. HF-BPCP combines the adhesive, structural, and bioactive features of fibrin sealants with the regenerative potential of PRP, offering a fully autologous alternative for clinical applications requiring rapid coagulation, high mechanical support, and sustained GF availability. Further preclinical and clinical studies are needed to evaluate therapeutic efficacy in the regenerative medicine field.

Background: In Europe, Vipera ammodytes ammodytes (Vaa, nose-horned viper) is considered the most venomous of the European vipers. The antivenom Viperfav®, composed of polyvalent equine F(ab′)2 fragments, is effective against Vipera aspis, Vipera berus and Vaa. Objectives: This study aimed to evaluate the clinical efficacy and pharmacokinetics of Viperfav in Vaa envenomations. Methods: Patients presenting with Vaa snakebite and treated with intravenous Viperfav were included. Clinical manifestations and laboratory findings were assessed on admission to the Emergency Department, prior to antivenom therapy, and monitored throughout hospitalization. Blood samples were collected on arrival and at defined intervals after Viperfav administration. Venom and antivenom concentrations in serum were determined by ELISA and subjected to pharmacokinetic analysis. Results: Twenty-one patients bitten by Vaa and classified with a severity score of 2b on the modified Audebert clinical severity scale received a single intravenous dose of Viperfav within 4 h of the bite. Viperfav attenuated the progression of local symptoms and prevented the development of new systemic manifestations. The serum concentrations of F(ab′)2 fragments reached 196 µg/mL, far exceeding the venom concentration at admission (35 ng/mL). The prolonged elimination half-life of Viperfav (49 h) corresponded with the absence of recurrent symptoms after a single dose. Bradycardia or hypotension occurred in 10% of patients; no cases of anaphylaxis or serum sickness were observed. Conclusions: A single intravenous dose of Viperfav demonstrated clinical efficacy and a favourable pharmacokinetic profile in Vaa envenomed patients when administered within hours of the bite.

Ultrasound therapy has emerged as a powerful tool for the non-invasive treatment of indications ranging from Parkinson’s disease and essential tremor to malignant solid tumours [...]

Background/Objectives: Here, we report the design, synthesis, and in vitro biological evaluation of a novel stimuli-sensitive nanotherapeutics based on cisplatin analog, cis-[PtCl2(NH3)(2-(3-oxobutyl)pyridine)] (Pt-OBP), covalently linked to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via a pH-sensitive hydrazone bond. Methods: Two polymer–drug conjugates, P-Pt-A and P-Pt-B, were synthesized, differing in spacer length between the polymer chain and hydrazone bond, which in turn modulates their drug release kinetics. Results: The spacer based on hydrazone bond demonstrated satisfactory stability under blood-mimicking conditions while enabling selective release of the active drug intracellularly or even in the mildly acidic tumor microenvironment. Pt-OBP exhibits comparable or even superior cytostatic and cytotoxic activity to carboplatin across a panel of murine and human cancer cell lines, with the highest potency observed in FaDu cells representing human head and neck squamous cell carcinoma. Mechanistically, Pt-OBP induced significant phosphorylation of γ-H2AX and activation of caspase-3, indicating its ability to cause DNA damage with subsequent apoptosis induction. P-Pt-A retained moderate biological activity, whereas the slower-releasing P-Pt-B exhibited reduced potency in vitro, consistent with its drug release profile. Conclusions: Notably, free Pt-OBP induced rapid apoptotic cell death, surpassing carboplatin at early time points, and the polymeric conjugates achieved comparable pro-apoptotic activity after extended incubation, suggesting effective intracellular release of the active drug.

Therapeutic resistance remains a critical barrier in oncology, frequently leading to cancer relapse after initial treatment response. Growing evidence suggests the presence of drug-tolerant persisters (DTPs), a rare subpopulation of cancer cells that survives chemotherapy by entering a reversible specific adaptation. Unlike classical cell resistance, the DTP phenotype is independent of genetic changes and maintained through dynamic regulatory mechanisms. DTPs are phenotypically heterogeneous and can exhibit stem-like and quiescent cell phenotypes, non- or slow proliferation, and remarkable plasticity due to a di-pause-like state and executing epithelial–mesenchymal transition (EMT) or transdifferentiation processes. Despite advances in research, the molecular mechanisms underlying DTPs’ biology and their role in cancer relapse remain only partially understood. The review summarizes the current progress in processes that lead to the acquisition of cellular persistence status, which, in turn, constitute areas of vulnerability that can be exploited in cancer therapy. We highlight anti-DTP therapeutic strategies, including epigenetic modification, cell signaling and transcriptional regulation, metabolic reprogramming, and modification of cell interactions within the tumor microenvironment. Furthermore, we focus on the potential role of nanomaterials in the combat against DTPs. Nanoparticles not only act as part of the drug delivery process, enabling precise DTP targeting and enhancing intracellular drug accumulation, but their intrinsic properties can also be used to eradicate DTPs directly or by enhancing the effectiveness of other therapeutic strategies. The integrated approach offers strong potential to eliminate tumor persistence, prevent recurrence, and improve long-term patient outcomes beyond conventional therapies.

Background: Alpha-linolenic acid (ALA) is an essential fatty acid from the omega-3 family that plays an important role in skin homeostasis. It is known for its anti-inflammatory properties, which can contribute to wound healing. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), may also play an important role in the skin, influencing nerve regeneration and pain modulation. Objectives: This article aims to explore the therapeutic effect of ALA on wound healing in streptozotocin-induced hyperglycemic mice, with an emphasis on the involvement of neurotrophins. Methods: We used keratinocyte cultures exposed or not to ALA and male C57BL6-J mice, which were randomly divided into four groups: non-hyperglycemic treated with vehicle; non-hyperglycemic treated with ALA; hyperglycemic treated with vehicle; and hyperglycemic treated with ALA. The treatment was administered continuously via a subcutaneous osmotic pump. Results: We found that controlled ALA administration potentiates the wound healing process in hyperglycemic mice by accelerating the inflammatory phase and promoting early granulation tissue formation (73.2% ± 0.7 vs. 92.2% ± 2.8 on day 7, n = 5; p < 0.05). This is supported by the balance between the expression of vimentin, CD31, and MMP-9. Furthermore, ALA modulates proteins linked to peripheral neurogenesis and gliogenesis, such as BDNF, NTRK2, SOX-10, CNTF, CTNFR, and STAT-3. It may also promote wound healing and nerve regeneration at the wound site in hyperglycemic animals. In non-hyperglycemic mice, ALA improves the quality of scars but does not accelerate the wound healing process, even with the positive modulation of certain genes relevant to skin healing. Conclusions: Alpha-linolenic acid improves skin wound healing and increases gene expression related to nerve regeneration in wounds of hyperglycemic mice.

Antimicrobial resistance (AMR) is a present, pressing global public health crisis associated with rising morbidity and mortality rates due to previously curable infectious disease. Targeted drug delivery is an important approach to address AMR due to its ability to improve the therapeutic performance of antibiotics without leading to any adverse effects or organ toxicities. In this review we explore molecular mechanisms of AMR and drawbacks of conventional antibiotic therapies and discuss unique drug delivery approaches to compensate these. Nanoparticulate carrier systems, stimuli-responsive systems, antibody–drug conjugates, and CRISPR-Cas systems are some of the carrier method designs that are promising for tackling hard to treat infections related to pathogenic strains and biofilms due to their features. Many of these are among the most significant advances in the field. However, there are many challenges to be overcome, with biological limitations, scaling and regulatory challenges, etc., before they can be employed in commercial applications. Materials are being developed, and an approach standardized and applicable to future work is in development to improve the efficiency of targeted delivery systems. Controlled drug delivery, which could be the answer to an increasing AMR problem, will not only help in alerting awareness among individuals but will also help in prolonging the activity of antibiotics by providing synergistic interdisciplinary solutions. This review emphasizes the complementary role of targeted drug delivery in transitioning from laboratory investigations to clinical therapy. It addresses underrepresented aspects, including new materials, scalability, regulatory considerations, and ethical implications, while offering a roadmap for translating innovations into next-generation antimicrobials.

Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary disease (COPD), asthma, neurodegeneration, and malignancy. Although broad-spectrum synthetic MMP inhibitors were initially developed as therapeutic agents, clinical trials failed due to lack of selectivity, poor tolerability, and impairment with physiological tissue repair. This outcome has shifted attention toward indirect pharmacological modulation of MMP-9 using drugs that are already approved for other indications. In this paper, we review the evidence supporting MMP-9 modulation by established therapeutics and adjunctive strategies. Cardiometabolic agents such as statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), metformin, and pioglitazone reduce MMP-9 expression and enzymatic activity, contributing to vascular protection, improved insulin sensitivity, and attenuation of aneurysm progression. Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways. In parallel, nutritional interventions—most notably omega-3 polyunsaturated fatty acids and antioxidant vitamins—provide adjunctive strategies for mitigating MMP-9 activity in chronic inflammatory states. Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing.