Local government debt has increasingly become a critical challenge for fiscal sustainability and the effective delivery of public services in Zambia. This paper undertakes aanalytical desk review of Local Government Public Debt in Zambia: Risk and Strategic Management Approaches. The review is guided by three objectives which are to evaluate the nature, scale, and composition of public debt among 116 local authorities in Zambia; to analyze the associated fiscal and economic risks of public debt at the local government level in Zambia, and recommend strategic management approaches aimed at enhancing debt sustainability and improving delivery of local services. The study is based on desk review which entailed a systematic and critical examination of national policy documents and official government reports related and /or incidental to the subject matter. Through a combination of qualitative and quantitative methodologies, quantitative analysis was used to examine trends and patterns in debt accumulation, while qualitative assessment captured contextual and institutional factors influencing debt management. The key findings revealed that public debt among 116 local authorities in Zambia is predominantly arrears-based rather than driven by formal borrowing, a substantial escalation in the scale of debt and arrears over the three-year period, with total verified obligations increasing from ZMW 4.38 billion in June 2022 to ZMW 5.86 billion by June 2025, representing a 33.86% rise. The findings indicate that arrears are not confined to a single expenditure category but are widespread across operational, statutory, and development-related obligations, underscoring the systemic nature of fiscal stress within local authorities. Statutory obligations, personnel-related arrears, and unpaid supplier and contractor liabilities constitute the largest components of local government debt, with urban and economically active councils generally exhibiting higher debt levels than rural councils. The analysis further established that the current structure of local government debt poses significant fiscal and economic risks. Rising statutory penalties and interest charges are eroding already constrained fiscal space, limiting resources available for service delivery and development expenditure. Increasing utility arrears heighten the risk of service disruptions and create contingent liabilities, while arrears to suppliers and contractors impose liquidity constraints on the local private sector, raise procurement costs, and weaken local economic activity. The reliance on arrears as an implicit financing mechanism undermines budget credibility and fiscal transparency, reinforcing a cycle of fiscal fragility at the local government level. Arising from the study’s findings, the study recommends several strategic management approaches to enhance debt sustainability, including debt restructuring, liquidation plans, strengthening revenue mobilization, budgetary controls, and institutionalized monitoring and evaluation mechanisms. Further, aligning recruitment and payroll policies with fiscal capacity and engaging with credit rating agencies can improve the financial credibility and borrowing capacity of local authorities. This study contributes to the literature by providing a comprehensive, evidence-based assessment of local government debt in Zambia, highlighting both its structural drivers and systemic risks. The findings have important policy implications, informing the design of debt management strategies, enhancing fiscal discipline, improving local service delivery, and supporting the broader decentralization agenda in Zambia

Introduction Chronic wounds related to diabetes incur significant morbidity and mortality, yet few effective therapies are available. Although whole body low-intensity vibration (LIV) has been shown to improve angiogenesis and wound healing in diabetic mice, local application of LIV signals could enhance the utility of this therapeutic approach. Methods The purpose of the present study was to compare the effectiveness of different treatment regimens involving local LIV applied to wounds of diabetic mice via oscillating motor, or by a wearable piezoelectric device. Results Local LIV delivered by oscillating motor enhanced angiogenesis, granulation tissue formation and wound closure to a similar degree for all vibration protocols tested. In addition, local LIV induced protocol-dependent increases in wound IGF1 and VEGF levels that did not necessarily correlate with the effects on healing. LIV delivered by piezoelectric disks involved accelerations that were an order of magnitude smaller than those delivered by the oscillating motor, but produced significant increases in angiogenesis and granulation tissue formation, with trends of enhanced wound closure. These changes were associated with increased VEGF but not IGF1 levels. Discussion These findings demonstrate that local delivery of LIV can enhance key aspects of diabetic wound healing, highlighting its potential as a non-invasive method for improving healing of chronic diabetic wounds.

Neutrophillic asthma, characterized by persistent airway inflammation and poor corticosteroid responsiveness, presents a significant therapeutic challenge. Repurposing rapamycin, an mTOR inhibitor, and simvastatin, a statin with anti-inflammatory effects, through targeted pulmonary delivery may provide a novel therapeutic strategy. A combinatorial dry powder inhalation formulation was developed by blending rapamycin and simvastatin with lactose carriers, and a Box–Behnken design was employed to optimize blending time, fine lactose content, and leucine content. Analytical characterization using FTIR, P-XRD, DSC, and SEM confirmed effective adsorption of actives onto lactose carriers with no significant drug–excipient incompatibilities. Aerodynamic evaluation demonstrated a fine particle fraction of 53.35% and 58.67% and a mass median aerodynamic diameter 2.037 µm and 4.307 µm, for simvastatin and rapamycin respectively indicating efficient pulmonary deposition. Stability studies showed acceptable stability for 6 months and in-vivo inhalational toxicity in healthy C57BL/6 mice confirmed safety. This preclinical proof-of-concept highlights the potential of localized pulmonary delivery to reduce systemic exposure while targeting inflammatory pathways in neutrophillic asthma. Further in vivo and translational studies are warranted to establish therapeutic efficacy. This approach provides a platform for repurposing simvastatin and rapamycin as an asthma treatment and addresses the unmet need in managing steroid-resistant asthma endotypes.

Recent updates in alginate as a promising biopolymer in cancer therapy: A review.

The periodontium is a uniquely dynamic tissue system requiring precise signaling for lifelong adaptation. The canonical Wnt/β-catenin pathway is a master regulator of bone homeostasis; however, its role in the specialized environment of the alveolar bone-marked by rapid turnover, complex mechanical forces, and exposure to the oral microbiome-remains incompletely understood, particularly in the context of aging. This review critically synthesizes evidence on Wnt signaling in alveolar bone remodeling, with a focus on age-related dysregulation, contrasting established paradigms from long bone biology with emerging oral-tissue-specific data. Wnt/β-catenin signaling is essential for periodontal homeostasis, orchestrating osteoblastogenesis and mechanotransduction. Its activity is compartment-specific within the periodontium and is potently suppressed in pathology. Key mechanisms of age-related decline include the upregulation of Wnt antagonists (e.g., sclerostin, DKK1), cellular senescence, altered FoxO-Wnt crosstalk under oxidative stress, and impaired mechanosensing. These changes converge to disrupt regenerative capacity, tipping the balance toward net alveolar bone loss. Therapeutically, sclerostin inhibition demonstrates robust preclinical efficacy in rescuing bone loss in models of periodontitis and estrogen deficiency. However, the potential cardiovascular risks of systemic Wnt activation suggest that redirecting efforts toward localized delivery strategies could be a promising alternative. Aging induces a multifaceted suppression of regenerative Wnt signaling in the periodontium. Modulating the Wnt pathway shows great potential for oral bone regeneration. However, significant challenges exist, especially in designing local delivery systems that are both safe and effective. Overcoming these hurdles is crucial for successful clinical applications. Future research must bridge the gap between skeletal biology and direct oral-specific investigations to enable targeted therapies that preserve periodontal health in an aging population.

ABSTRACT Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for arterial and venous disease management. Here, we present EndoBot, an untethered elastic millirobot designed to enable endothelial‐safe, soft‐contact operation, under physiologic blood flow. EndoBot is magnetically actuated and navigates along the vessel lumen through curved, non‐uniform geometries while maintaining ultra‐low radial contact pressures (<1 kPa), far below endothelial injury thresholds. We demonstrate stable locomotion, with intrinsically compliant mechanics within a defined safety envelope under arterial and venous hemodynamics in phantom vessels, ex vivo human umbilical veins, and an in vivo rat inferior vena cava, without detectable vessel damage. EndoBot is compatible with standard vascular sheaths for wireless deployment and retrieval and is controlled under clinical fluoroscopic guidance using a human‐scale magnetic manipulation platform. Blood compatibility testing confirms safety, with minimal hemolysis and no increased coagulation tendency during navigation. For localized therapy, EndoBot employs a gentle endoluminal painting strategy, transferring a washout‐resistant drug depot directly onto the vessel lumen. By combining atraumatic mobility, clinical deployability, and localized drug deposition, EndoBot establishes a translationally viable platform for developingmaintenance‐oriented endovascular therapies, supporting prevention of restonosis, thrombosis and inflammatory remodeling following intervention.

This study evaluated the protective effect of combining Bifidobacterium bifidum with the prebiotics inulin and isomalto-oligosaccharides against enterohemorrhagic Escherichia coli infection and investigated the underlying mechanisms, using an integrated strategy of in vitro screening followed by in vivo validation. Among ten prebiotics screened, IMO and inulin were identified as optimal for promoting B. bifidum proliferation and acetate production (>2.5-fold), with IMO further enhancing bacterial adhesion to Caco-2 cells (4-fold). In a murine infection model, B. bifidum alone reduced total intestinal EHEC colonization, whereas inulin alone was ineffective. The combination of IMO and B. bifidum markedly suppressed EHEC colonization, particularly in the colon (5-fold reduction), while inulin provided no added benefit. Although fecal acetate levels were elevated in synbiotic groups, no linear correlation with EHEC clearance was observed, suggesting that protection may rely on mechanisms other than bulk acetate production-such as localized metabolite delivery or microbial ecological interactions. These findings demonstrate that an IMO-based synbiotic can effectively limit EHEC colonization through multifactorial modulation of the gut ecosystem. The presented strategy offers a rational framework for designing synbiotics to prevent foodborne infections.

Mesoporous silica (MS) is widely recognized as a local drug delivery system in bone-related diseases. Although MS enables controlled or sustained release and improved bioavailability of therapeutic agents, its limited native osseointegration capacity remains a critical barrier to effective bone regeneration. Numerous engineering strategies have therefore been proposed to enhance its biological performance. This scoping review protocol aims to collect studies, published from January 2015 onwards, that report evidence on the osseointegration potential (i.e., osteoconductive, osteoinductive, or proangiogenic properties) of MS bone drug delivery systems. Studies indexed in PubMed, Scopus, and Embase will be screened to identify the strategies used to improve MS-mediated bone regeneration, including structural modifications, formulation into composites, and incorporation of bioactive molecules. A structured analytical framework will be applied to explore how specific design approaches relate to biological outcomes across experimental models in vitro, in vivo, or ex vivo. The resulting scoping review will identify trends and knowledge gaps in strategies intended to enhance the osseointegration of MS bone drug delivery systems, supporting their future development and rational optimization for bone repair.

Peripheral nerve injuries (PNIs) remain a major clinical and socioeconomic challenge, frequently resulting in motor weakness, sensory loss, and chronic neuropathic pain that cause long-term disability and restrict daily function. Functional recovery is limited by slow axonal regrowth, Wallerian degeneration, interstitial fibrosis, and progressive denervation-induced muscle atrophy. Although microsurgical epineurial repair and autologous nerve grafting are standard treatments, clinical outcomes remain inconsistent, especially in long-gap or delayed repairs. These limitations underscore the need for more effective regenerative strategies that address both the structural and biological barriers to nerve recovery. Contemporary research on PNIs focuses on four interconnected domains: structural reconstruction, biological acceleration, functional remodelling, and anatomical restoration. Advanced nerve-guidance conduits offer biomimetic, aligned pathways that reduce axonal misdirection and complement microsuture or autograft repair. Biological approaches, including localized delivery of neurotrophic factors, mesenchymal stem cells, induced-pluripotent stem cell derivatives, and their exosomes, enhance Schwann cell reprogramming, angiogenesis, and pro-regenerative immune polarization while reducing risks associated with live cell transplantation. Non-invasive biophysical stimulation modalities, such as electrical stimulation, magnetic fields, photobiomodulation, low-intensity pulsed ultrasound, and piezoelectric scaffolds, further promote axonal growth and neurotrophic signaling. Emerging integrated strategies that combine stem cell-derived exosomes with physical cues demonstrate synergistic regeneration in preclinical models, representing promising avenues for treating critical-sized nerve gaps. Multi-omics technologies, including transcriptomics, proteomics, metabolomics, and spatial profiling, have deepened mechanistic understanding of Schwann cell plasticity, axon-glia communication, and injury-induced inflammatory dynamics. However, clinical translation remains constrained by heterogeneity in study design, biomaterial manufacturing, regulatory requirements, and the lack of validated biomarkers for monitoring nerve regeneration. Overcoming these obstacles will require coordinated efforts across surgery, biomaterials engineering, stem cell biology, pharmacology, neuromodulation, and rehabilitation medicine. Recent progress in biomaterial conduits, cell-free biologics, and biophysical stimulation is transforming PNI treatment and providing options that surpass conventional microsurgical repair. Continued advancement will require reliable biomarkers, standardized production and evaluation methods, and well-designed randomized controlled trials. Coordinated collaboration across research, clinical practice, industry, and regulatory agencies is essential to develop safe, effective, and widely applicable neuroregenerative therapies that restore meaningful function after peripheral nerve injury.

Oral squamous cell carcinoma (OSCC) remains a challenging malignancy with high recurrence and metastasis rates, often limited by insufficient immunogenicity and a suppressive tumor microenvironment. Immunogenic cell death (ICD) offers a promising approach to convert cell death into antitumor immunity; yet, its efficacy depends on precise modulation of autophagy and endoplasmic reticulum stress (ERS). Here, we report that combining the BET inhibitor JQ1 with the autophagy inhibitor chloroquine (CQ) synergistically amplifies ERS, leading to enhanced ICD in OSCC models. This combination promotes robust damage-associated molecular pattern (DAMP) release, dendritic cell activation, and antigen-specific CD8+ T-cell responses. To enable localized and efficient delivery, we engineered self-assembled JQ1/CQ nanoparticles stabilized through π-π stacking and integrated them into dissolvable cryomicroneedles. This minimally invasive platform ensures sustained drug release, improves tumor accumulation, and minimizes systemic exposure. Our study not only elucidates a druggable autophagy-ERS-ICD axis but also provides a versatile transdermal delivery strategy with potential applicability to a range of solid tumors.

Biomedical implants play a critical role in restoring tissue function; however, their long-term performance is often hindered by challenges such as infection, inflammation, and poor integration with the host tissue. Recent advances in polymer-based coatings, particularly those incorporating drug-loaded microparticles and nanostructured fillers, have demonstrated outstanding potential in overcoming these limitations. These multifunctional coatings not only enhance biocompatibility and mechanical stability but also enable controlled, localized drug delivery, thereby reducing systemic side effects and improving therapeutic outcomes. This review differentiate three different categories of polymer coatings which can be mostly found in research works including: Natural polymers with their remarkable promise due to their biodegradability, inherent bioactivity, and ability to support cell adhesion and tissue regeneration; Synthetic polymers, which can further contribute tunable degradation rates and mechanical versatility, making them suitable for a wide range of clinical applications; Hybrid/composite coatings, whose design rely on integrating both natural and synthetic polymers to enable to tackle more bottlenecks and expand the therapeutic scope of implants by providing infection resistance, anti-inflammatory effects, and osteogenic stimulation. Furthermore, this review brings together recent advances in micro- and nanoengineered drug-eluting coatings for medical implants, highlighting their design strategies, functional performance, and clinical relevance. Emerging trends and future directions are discussed to underscore the transformative potential of these systems in advancing next-generation implantable medical devices.

Inclusion of physiologically relevant clearance mechanisms into organ-on-a-chip models is essential to reproduce tissue exposure and predict therapeutic efficacy, especially for local therapies and drug delivery applications that are already common in the clinic for ocular and cancer treatments. There remains a need for clearance-enabled organ-on-a-chips amenable to high throughput screening, especially with the emerging trend to expedite formulation and drug delivery vehicle (DDV) design with machine learning. To address this gap, we developed a microfluidic platform that incorporates continuous, pressure-driven clearance through interconnected microchannels and three-dimensional (3D) systems, enabling translational evaluation of local therapies and DDVs, such as injectable hydrogels, that aim to reduce systemic toxicity and enhance efficacy by prolonging drug residence at disease sites. In this study, fluorescent 4 and 65 kDa dextrans were used to confirm that pressure gradients across the platform promote efficient clearance versus passive diffusion. The pressure gradients were then applied to breast cancer spheroids co-cultured with macrophages in a fibrin hydrogel to evaluate the therapeutic efficacy of an interferon gamma (IFN-γ)-releasing agarose hydrogel in combination with anti-human epidermal growth factor receptor 2 (anti-HER2). Fluorescent imaging of spheroid area revealed increased cancer cell viability, lower drug efficacy, when continuous clearance was present, highlighting the impact of drug clearance. This study establishes the clearance-enabled microfluidic platform as a translationally relevant in vitro model for evaluating local therapies under continuous clearance, thereby bridging the gap between traditional static platforms and in vivo models for evaluating local pharmacokinetics and pharmacodynamics.

Small interfering RNAs (siRNAs) offer significant therapeutic potential; however, extrahepatic applications, particularly to the skin, remain a challenge. Limited work has explored siRNA therapies for the skin, the largest organ in the human body, where dermatological conditions affect over one-third of the population worldwide. The skin's external location makes it easily accessible for direct, local administration. Here, we present the in vivo intradermal delivery of therapeutic siRNAs into a porcine model whose skin structure most closely resembles that of human skin, demonstrating functional, and sustained gene silencing. We characterize two siRNA conjugates in human ex vivo and porcine in vivo skin models, showing that increased hydrophobicity significantly enhances skin retention and efficacy of siRNAs. Using a validated JAK1-targeting compound, we demonstrate that local delivery of siRNA enables accumulation across multiple cell types and suppression of JAK1-dependent inflammatory pathway in human skin ex vivo. In porcine models, intradermal injections result in prolonged skin siRNA retention for more than eight weeks, limited systemic tissue exposure, and sustained gene silencing for at least one month. These results underscore the importance of tailored siRNA conjugate design for achieving optimal skin biodistribution and therapeutic efficacy, providing a foundation for siRNA-based treatments for a broad range of dermatological conditions.

Radiation-induced proctitis is a common complication of radiotherapy for pelvic malignancies, for which effective local treatments remain limited. Epigallocatechin gallate (EGCG) has antioxidant and anti-inflammatory activities but is limited by poor stability and bioavailability. This study aimed to develop a stable, rectally deliverable EGCG-based formulation to mitigate radiation-induced rectal injury. An EGCG-zinc (EGCG-Zn) nanocomplex was prepared via metal-polyphenol coordination and formulated into a thermosensitive rectal suppository for localized delivery. Zinc coordination significantly improved EGCG stability while preserving its antioxidant activity. The suppository enabled prolonged rectal residence and enhanced local drug exposure. In irradiated mouse models, EGCG-Zn suppositories reduced oxidative stress, DNA damage, and inflammatory responses in rectal tissue, and promoted epithelial regeneration and tight junction restoration. Transcriptomic and molecular analyses suggested involvement of inflammation-related and epithelial barrier-associated signaling pathways. No detectable local or systemic toxicity was observed after repeated administration. These findings indicate that an EGCG-Zn-based thermosensitive rectal suppository is a safe and effective localized strategy for alleviating radiation-induced proctitis, with potential translational value for the management of radiation-associated rectal injury.

Implantation of intracortical microelectrodes generates free iron species that exacerbate pro-inflammatory responses by producing reactive oxygen species through the Fenton reaction. This work reports a covalently grafted, two-layer poly(ethylene glycol)dimethacrylate (PEGDMA) hydrogel on polyimide-insulated Pt/Ir microwires for local delivery of the iron chelator deferasirox (DFO). The polyimide insulating layer was methacrylated to enable covalent anchoring of a PEGDMA550 interlayer, followed by a DFO-loaded PEGDMA3400 outer layer. Scanning electron microscopy and optical microscopy of the hydrogel-coated microwires revealed a uniform coating morphology with dispersed DFO aggregates embedded within the matrix. In buffer at 37 °C, DFO release followed diffusion-controlled kinetics and fell below the limit of detection by ultraperformance liquid chromatography by day 9. The iron-chelation properties of the DFO-loaded microwires were investigated using Fe(EDTA) as a free-iron mimic. When a high concentration of Fe(EDTA) was used (10 mM), the Fe(DFO)2 complex remained detectable for up to 19 days, which expands well beyond the detection limit of DFO under iron-free conditions (9 days). Energy-dispersive X-ray spectroscopy showed time-dependent iron accumulation within the hydrogel, consistent with in-matrix complexation that perturbs local transport and prolongs chelation efficacy. Collectively, the coating functions as a mechanically integrated, responsive reservoir whose pharmacokinetics are governed by the iron concentration rather than initial drug loading. By coupling chelation capacity to local iron availability, the presented hydrogel coating establishes a generalizable route to extend therapeutic lifetimes of functionalized chronic neural electrodes.

Abstract To develop a green and functional hydrogel for potential application as a wound dressing, in this study, composite hydrogels were prepared using corn starch and chitosan as the matrix, with citric acid (CA) at a series of concentrations (5%—20%, w/w) serving as a green crosslinking agent. Resveratrol (Res) was loaded into these hydrogels, and the influences of CA concentration on the swelling and gel characteristics of the composite hydrogels were systematically investigated. The results demonstrated that the hydrogel crosslinked with 10% CA (designated as SCA10%) exhibited the optimal comprehensive performance, achieving an equilibrium swelling ratio of 228% and appropriate gel strength. Structural analysis confirmed the formation of crosslinking between CA and starch/chitosan, as well as the successful loading of Res into the hydrogel matrix. Notably, microscopic images revealed that the incorporation of Res resulted in a more well-developed and uniform porous structure in SCA10%-Res. Additionally, this composite hydrogel showed robust antibacterial activity. Collectively, the prepared starch-chitosan-CA-Res hydrogel holds significant potential for applications in wound repair and localized drug delivery. It also provides a valuable reference for the green fabrication of natural polymer-based functional materials.

To review the effects of perioperative steroid delivery on cochlear impedances in human patients. PubMed, Web of Science, Embase, Ovid, and Cochrane databases were reviewed from inception through March 2025. The Preferred Reporting Items for Systematic Reviews (PRISMA) reporting guidelines were used. Studies comparing cochlear impedances among patients who underwent cochlear implantation either with or without perioperative steroids were included. Data were collected on method, timing, and dose of steroid administration and cochlear impedance in the perioperative period. Twelve studies were included in the review, which described 4 different routes of steroid delivery: intratympanic (3), intracochlear (7), drug-eluting electrodes (1), and intravenous±oral steroids (1). Nine studies revealed a significant association between steroid use during at least one point in the perioperative period to include 2 intracochlear studies and the intravenous±oral steroids study. Intratympanic steroid delivery reduced impedances up to 6 months postoperatively, whereas intracochlear and drug-eluting electrodes had persistent reductions in impedance up to 1 year. There was significant heterogeneity in study outcomes that limited the ability to perform a meta-analysis. Based on studies meeting inclusion criteria, local delivery of steroids via intratympanic, intracochlear, and drug-eluting formulations appear to lower cochlear impedances for a variable duration postoperatively. Oral steroids do not appear to affect cochlear impedances postoperatively. More studies are necessary to further elucidate the relationship between steroids and cochlear impedance.

Sustained and localized delivery of gemcitabine using chitosan-PVA-TPP polymeric implant enhances antitumor efficacy and delays surgical relapse in pancreatic cancer.

Lipid nanoparticle-mediated delivery of microRNA-124 reduces neuroinflammation.

Hydrogel delivering antifibrotic agent and nano-sonosensitizer enhances efficacy of sonodynamic therapy in osteosarcoma treatment.