Search Results (2,303)

Periprosthetic joint infection (PJI) remains one of the most serious complications of arthroplasty, largely due to the formation of microbial biofilms on implant surfaces. Biofilm-associated infections exhibit increased tolerance to antimicrobial therapy and host immune responses, making eradication difficult and often requiring repeated surgical interventions. Consequently, there is a growing need for effective local therapeutic strategies capable of delivering high concentrations of antimicrobial agents directly to the site of infection while minimizing systemic toxicity. Hydrogels have emerged as promising drug delivery platforms for the management of biofilm-associated PJI. Their biocompatibility, injectability, high water content, and tunable physicochemical properties enable controlled and localized release of therapeutic agents within the infected peri-implant environment. This narrative review summarizes recent advances in hydrogel-based approaches, including antibiotic-loaded hydrogels, systems incorporating anti-biofilm enzymes, bacteriophage-loaded formulations, and nanoparticle-enhanced platforms. It also highlights future research directions, with particular emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Particular attention is given to stimuli-responsive (“smart”) hydrogels that release therapeutic payloads in response to infection-related triggers such as pH changes, with emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Full article

The development of nanoparticle (NP)-based drug delivery systems that combine passive tumor targeting, physiological stability, and therapeutic efficacy remains a key challenge in cancer nanomedicine. Here, we report a pH-responsive peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) NP system designed for cancer targeting. The PLGA core is coated with a short glutamic acid–lysine–histidine–phenylalanine x3 (EKHFFF) peptide shell, enabling tunable surface charge modulation around its isoelectric point and promoting environmental responsiveness. Physicochemical characterization confirms spherical NPs (~70–75 nm) with good colloidal stability, serum compatibility, and ion-dependent stability in physiological conditions. The peptide coating also provides pH-dependent modulation of the zeta potential. Evaluation of the NPs in ovarian cancer (OvCA) models, including immortalized and patient-derived cell lines (PDCLs), demonstrates efficient uptake across OvCA cell lines, with significantly enhanced internalization in PDCLs compared to immortalized cells. The EKHFFF nanoparticle (EKHFFF NP) induced minimal reactive oxygen species and nitric oxide production in macrophages, indicating low immunogenicity and favorable biocompatibility. Upon platinum loading (EKHFFF-Pt NP), the system exhibits potent cytotoxicity in both platinum-sensitive and platinum-resistant OvCA cell lines, outperforming carboplatin and showing comparable or improved efficacy relative to cisplatin in several cell lines. In vivo studies further demonstrate preferential tumor accumulation, sustained intratumoral retention, and measurable systemic circulation with a half-life of approximately 35 min. Full article

Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug delivery systems with enhanced therapeutic efficacy, targeted delivery, improved bioavailability, and reduced systemic toxicity. Recent advances in MSN synthesis, physicochemical properties, surface engineering, and functionalization strategies have significantly improved their biological performance and therapeutic potential. In particular, integrating polymers, lipids, and liposomes with MSN platforms has enhanced colloidal stability, circulation time, cellular uptake, and target specificity, thereby facilitating efficient, stimuli-responsive drug delivery. This review highlights MSN-based drug delivery systems in cancer therapy, where multifunctional nanocarriers enable site-specific delivery, controlled drug release, enhanced tumor accumulation, and reduced off-target effects. The review discusses the expanding roles of MSNs in antimicrobial therapy, wound healing, tissue engineering, and regenerative medicine, emphasizing their ability to promote localized therapeutic delivery, immunomodulation, angiogenesis, and tissue regeneration. The review discusses the diagnostic and theragnostic capabilities of MSNs for disease imaging and monitoring. It also critically evaluates current challenges related to biocompatibility, biodegradation, toxicity, biological barriers, large-scale manufacturing, clinical translation, and regulatory considerations. This review provides a comprehensive overview of recent progress, current limitations, and future opportunities for MSN-based platforms in targeted drug delivery and advanced biomedical applications, supporting their continued advancement toward clinical translation and precision medicine. Full article

Drug delivery systems (DDSs) have attracted significant attention due to their ability to enhance therapeutic efficacy while minimizing side effects. In this study, vancomycin (VCM)-loaded calcium phosphate-liposome (CaPLip) composite nanoparticles were developed as a pH-responsive drug delivery system. The CaPLip nanoparticles were fabricated by in situ calcium phosphate precipitation on preformed liposomal templates in the presence of VCM, allowing the drug to be incorporated within the calcium phosphate matrix and adsorbed onto the CaP-coated surface (VCM-CaPLip). Structural and morphological characterization using FT-IR, XRD, and TEM confirmed the successful formation of calcium phosphate-coated liposomal nanoparticles with particle sizes ranging from 300 to 700 nm and a negative surface charge. The developed system exhibited an overall drug-loading efficiency of 47.28% and effectively reduced the initial burst release under physiological conditions. Equilibrium adsorption studies performed using preformed CaPLip nanoparticles demonstrated that VCM adsorption was well described by the Langmuir isotherm, indicating a high affinity of VCM for the CaP-coated surface under equilibrium conditions. Drug release studies at pH 4.0, 6.5, and 7.4 revealed pronounced pH-dependent behavior, with sustained release at pH 7.4 and accelerated release under acidic conditions. Changes in electrical conductivity provided supporting evidence for calcium phosphate dissolution accompanying drug release under acidic conditions. Kinetic analysis indicated a transition from predominantly diffusion-controlled release at physiological pH to diffusion-dissolution coupled release under acidic conditions. These findings demonstrate that CaPLip nanoparticles provide an effective pH-responsive antibiotic delivery platform and show potential for controlled drug release in infection-associated mildly acidic microenvironments. Full article

Silicone elastomers are attractive matrices for transdermal drug delivery systems, but the controlled release of poorly water-soluble drugs from hydrophobic silicone networks remains challenging. Medical-grade silicone elastomers are generally regarded as chemically stable, biologically inert, and highly biocompatible polymer matrices, which supports their use in biomedical and pharmaceutical materials. Here, ibuprofen-loaded silicone/polyol composite films were prepared from hydroxyl-terminated polydimethylsiloxane (PDMS-OH) using glycerol- and 1,2-propylene glycol-derived alkoxysilane cross-linkers and amino-terminated PDMS as a metal-free room-temperature-vulcanising catalyst. The effects of cross-linker composition, glycerol, PEG 200 and selected functional additives on film formation, morphology, apparent ibuprofen release and preliminary Strat-M^® permeation were evaluated. FTIR analysis indicated no covalent reaction between ibuprofen and the silicone network, but suggested hydrogen-bonding interactions with polyol-rich domains, particularly in glycerol-containing systems. Raman mapping supported ibuprofen incorporation within the films, while SEM showed phase-separated microdomains whose morphology depended on the formulation. Apparent release into 0.9% NaCl at 37 °C was formulation-dependent over 72 h. The optimised F-9 film showed approximately 83% cumulative apparent release, whereas the F-10 film containing copper oxide nanoparticles and sea buckthorn oil showed the highest numerical cumulative apparent release, approximately 94%. Kinetic analysis of the apparent release data supported a mainly diffusion-controlled contribution, modulated by hydrophilic microdomains. These results provide preliminary materials-development evidence that silicone/polyol films can be used to tune apparent ibuprofen release and merit further optimisation for local topical or transdermal applications; however, efficient skin permeation and biological performance require dedicated validation. Full article

Background: Lipid nanoparticles are widely investigated as oral drug delivery systems, but their intestinal performance remains difficult to predict based only on physicochemical properties. This study aimed to elucidate how the lipid matrix composition influences the intestinal permeation of curcumin from lipid nanoparticles. Methods: Curcumin-loaded nanoemulsions, nanostructured lipid carriers with defined solid-to-liquid lipid ratios, and solid lipid nanoparticles were prepared by high-pressure homogenization. All formulations were characterized with respect to particle size, polydispersity index, and zeta potential before and after simulated intestinal pre-incubation in a simplified SDS-containing intestinal fluid. Intestinal permeation was evaluated ex vivo using porcine gut tissue by analysis of semi-quantitative fluorescence-based permeation readouts (ART) and mean permeation depth (MPD) after 30 and 60 min. Results: All formulations maintained stable physicochemical properties with particle sizes around 200 nm and negative zeta potentials; pre-incubation increased the negativity of the zeta potential but left particle size unchanged. Despite similar attributes, the formulations differed in intestinal curcumin permeation based on time and composition. At 30 min, nanoemulsions and mixed nanostructured lipid carriers achieved the highest performance. By 60 min, lipid carriers with more liquid lipid significantly increased both the fluorescence intensity and the depth of curcumin permeation, while other systems showed little further improvement. Conclusions: The intestinal permeation of drug from lipid nanoparticles is governed by the lipid matrix architecture and its interaction with the hydrated intestinal environment, which together affect drug-release kinetics and the ability to sustain a trans-epithelial concentration gradient over time. Thus, optimizing oral lipid nanoparticles requires time-resolved, biologically relevant models rather than physicochemical characterization alone, consistent with observed similar matrix-driven effects in dermal delivery systems. Full article

Magnetothermally responsive nanocarriers represent a promising platform for spatio-temporally controlled drug delivery by combining alternating magnetic field (AMF)-induced heating with thermally triggered cargo release. Among the available architectures, magnetite-core/mesoporous-silica-shell (Fe₃O₄@mSiO₂) nanoparticles functionalized with thermoresponsive polymer gatekeepers are particularly attractive. These systems integrate a magnetic heat source, a mesoporous drug reservoir, and temperature-dependent control of pore accessibility. This review examines the fundamental principles of magnetic hyperthermia, including heat-generation mechanisms, specific absorption rate (SAR), intrinsic loss power (ILP), AMF parameters and safety, and the interplay between Néel and Brownian relaxation. It also critically discusses core–shell synthesis and architecture, drug-loading strategies, PNIPAM-, PNVCL-, and other LCST-type gatekeepers, and the physicochemical characterization required to validate the complete nanocarrier. Evidence for combined magnetic hyperthermia and chemotherapy is assessed together with hemocompatibility, immunogenicity, oxidative stress, biodistribution, degradation, long-term retention, and clearance. Although promising magnetothermal release and therapeutic effects have been reported, evidence remains dominated by in vitro studies, with limited in vivo validation. Current clinical experience concerns locally administered iron-oxide hyperthermia rather than complete thermoresponsive Fe₃O₄@mSiO₂ drug-delivery systems. Translation will require standardized magnetothermal and release testing, reproducible scale-up, validated sterilization and endotoxin control, component-resolved pharmacokinetics, and integrated development of the nanocarrier and AMF applicator. Full article

Melanin nanoparticles (MNPs) have attracted growing attention in biomedical fields due to their wide bioavailability, high biocompatibility, biodegradability, and multifunctionality. Key features of MNPs are broad-spectrum light absorption, high drug-loading capacity, near-infrared light-triggered drug release and reactive oxygen species generation, efficient hepatobiliary, renal clearance, and superior binding affinity towards metal ions that enhance MNPs’ traceability in magnetic resonance imaging (MRI). Despite challenges such as agglomeration in time, lack of extraction standardization, and a limited number of animal and clinical studies, the strong photothermal conversion and reactive species production abilities of MNPs make them effective photosensitizers and photothermal agents, while their dual capability for molecular binding and metal chelation positions them as promising agents for theranostic applications. This review provides a comprehensive overview of MNPs, covering their structural features, manufacturing methods and associated limitations, and recent advances in their physicochemical characterization. Special focus is given to MRI-guided biomedical applications, including drug delivery, photothermal therapy, and photodynamic therapy, along with critical challenges related to the clinical translation and commercialization of MNP-based platforms. By consolidating recent advances, this review highlights key structure–function relationships that underpin emerging melanin-based nano-systems. Full article

Conventional oral and injectable drug administration still struggles with unstable plasma levels, weak targeting, and considerable systemic toxicity, problems that become especially acute in chronic disease management. Implantable and wearable biomedical devices offer one path around these limits, yet device-only platforms continue to fall short on drug loading, release control, and protection of fragile therapeutics. Integrating nanoparticle-based biomaterials into such devices has therefore moved from a research curiosity to a serious clinical strategy. As a result, understanding the design principles, translational challenges, and clinical potential of these hybrid platforms has become increasingly important. This review provides a comprehensive assessment of four major nanoparticle families—polymeric carriers (PLGA, chitosan, and micelles), lipid-based vehicles (liposomes, SLNs, and NLCs), inorganic systems (gold, mesoporous silica, iron oxide, and calcium phosphate), and hybrid composites—focusing on how their physicochemical properties govern drug encapsulation, release behavior, and tissue compatibility. These classes are then linked to specific implantable formats such as drug-eluting stents, nano-enabled scaffolds, and reservoir depots, and to wearable formats including transdermal patches, microneedle arrays, biosensor-coupled patches, and patient-actuated devices. A dedicated section addresses stimuli-responsive release driven by pH, enzymes, temperature, and electrical or magnetic fields, alongside closed-loop platforms that pair real-time biosensing with on-demand dosing. Surface engineering strategies, ligand targeting, antifouling coatings, antimicrobial layers, and immune-modulating chemistries are also discussed, together with the central translational hurdles: long-term stability, foreign body response, scale-up, sterilization, and regulatory classification of combination products. Finally, the review outlines near-term directions, including AI-driven dosing, 4D bioprinting, biomimetic nanocarriers, gene therapy delivery, and bioresorbable electronics, that together suggest where these hybrid platforms are likely to mature next. Full article

Background: Hepatocellular carcinoma (HCC) remains challenging to treat because of the limited therapeutic efficacy and insufficient selectivity of conventional therapies. To overcome these limitations, multifunctional nanoplatforms integrating biomimetic strategies and combination therapy have attracted increasing attention. Single-modality therapies are often limited by insufficient therapeutic efficacy and restricted mechanisms of action, highlighting the need for biomimetic nanoplatforms that integrate combination therapeutic strategies for enhanced antitumor performance. Methods: Herein, a biomimetic strategy-based nanoplatform (DI-ZM) was constructed via a combination of ZIF-8 biomineralization, physical adsorption of dihydroartemisinin (DHA) and indocyanine green (ICG), followed by HepG2 cell membrane coating to achieve homologous interaction. This design enables integrated chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) within a single system. Results: The resulting DI-ZM nanoparticles exhibited a hydrodynamic diameter of approximately ~200 nm with good colloidal stability and high drug-loading capacity. Under 808 nm laser irradiation, DI-ZM achieved a temperature elevation to ~66 °C within 5 min, together with efficient ROS generation. Compared with uncoated nanoparticles, the biomimetic membrane coating significantly enhanced cellular uptake and homologous targeting ability, as confirmed by CLSM and flow cytometry analysis. Benefiting from the biomimetic membrane coating, DI-ZM further exhibited improved homologous targeting and cellular uptake, which contributed to enhanced intracellular ROS generation. This was accompanied by significant mitochondrial membrane depolarization and apoptosis rates exceeding 80% in HepG2 cells under laser irradiation, ultimately resulting in markedly enhanced cytotoxicity. In addition, the biomimetic membrane coating also enabled efficient penetration of DI-ZM into multicellular tumor spheroids, indicating its improved tumor-penetration capability. In vivo antitumor studies further revealed effective tumor suppression with a tumor inhibition rate of approximately 97%, along with acceptable systemic tolerance in HepG2 tumor-bearing mice. Conclusion: The biomimetic membrane-coated ZIF-8 nanoplatform integrating chemotherapy with ICG-mediated phototherapy (photothermal and photodynamic therapy) provides an effective strategy for the combination therapy against HCC. Full article

Background/Objectives: Intervertebral disc degeneration (IDD) is a major cause of chronic low back pain and disability. Nuciferine, a natural alkaloid with mitochondrial protective activity, shows therapeutic potential for IDD. However, the avascular nature of intervertebral discs limits effective drug delivery. This study aimed to develop a hierarchical stimuli-responsive microneedle (MN) system for localized nuciferine delivery. Methods: Nuciferine-loaded lipid nanoparticles (LNPs) were embedded in a phenylboronic acid-modified hyaluronic acid (HA-PBA) matrix to construct functional MNs. LNP characteristics and drug release were evaluated under physiological and simulated degenerative conditions. The effects of released LNPs on nucleus pulposus cell (NPC) viability, mitophagy, oxidative stress, and extracellular matrix homeostasis were assessed in vitro. Therapeutic efficacy was further evaluated in a rat IDD model. Results: Nuciferine-loaded LNPs had a mean size of 86.54 nm, PDI of 0.108, and encapsulation efficiency of 75.65%. The HA-PBA MNs showed minimal drug release at pH 7.4 but markedly accelerated release under dual stimuli (100 μM H₂O₂ and pH 5.0). Released LNPs maintained NPC viability above 90%, enhanced mitophagy by increasing LC3B-II and decreasing P62, and alleviated oxidative damage and extracellular matrix imbalance. In vivo, MN treatment significantly preserved the disc height index and improved Pfirrmann grades compared with the IDD group (p < 0.05). Conclusions: The hierarchical stimuli-responsive MN system enables localized, pathological microenvironment-responsive nuciferine delivery and protects against IDD by promoting mitophagy, reducing oxidative damage, and restoring extracellular matrix homeostasis. This strategy provides a potential approach for localized treatment of IDD. Full article

Prostate cancer (PC) is one of the most common cancers in men globally and there is an urgent need for new immune-based approaches because many traditional therapies, including chemotherapy, radiotherapy, and anti-androgens, have limitations. Due to their distinct physicochemical and biological features, gold nanoparticles (AuNPs) are emerging as a potential nanoplatform for the development of strategies in prostate cancer therapy. These features include tunable size, shape, and surface plasmon resonance (SPR) and high surface-to-volume ratio, which result in enhanced drug loading, targeted delivery and improved bioavailability. In addition, AuNPs can also be functionalized for active targeting to promote selective accumulation in tumors while minimizing systemic toxicity. In addition, the intrinsic optical and photothermal properties of these nanoparticles allow them to serve for PTT, radiosensitization and multimodal imaging, i.e., CT (computed tomography) and photoacoustic imaging. These have shown potential in pre-clinical and clinical evaluation but face issues with long-term toxicity, biodistribution and large-scale manufacturing. In this review, we summarize the organizing features, functional properties, therapeutic activities and translational potentials of AuNPs in prostate cancer treatment, with emphasis on their contributions towards precision nanomedicine. Full article

Accurate measurement of messenger RNA (mRNA) concentration and encapsulation efficiency remains a challenging task during mRNA-lipid nanoparticle (LNP) formulation development and quality control. RiboGreen-based fluorescence assays are often used for this purpose. LNP formulations are colloidal systems and may exhibit turbidity, which can interfere with fluorescence detection. The impact of LNP-related optical properties on assay performance remains insufficiently characterized. This study aimed to evaluate whether and how physicochemical factors associated with LNP-based drug-delivery systems influence fluorometric mRNA quantification. Empty LNPs, with the same lipid composition as mRNA-loaded LNPs, were used as a model matrix causing turbidity. Their effect on the RiboGreen fluorescence signal was assessed following dilution and then in different scenarios in the presence of free and encapsulated mRNA. The UV–Vis spectrum of the placebo dispersion was recorded to examine possible optical interference in the measurement range. We quantitatively characterized the suppression of fluorescence signals in the presence of LNPs in a concentration-dependent manner. These findings indicate that turbidity and LNP-associated matrix effects can bias RiboGreen-based mRNA quantification. To ensure reliable determination of mRNA concentration and accurate calculation of encapsulation efficiency in LNP formulations, method-specific dilution factors should be applied. Full article

Background/Objectives: Skin cancer is a major health concern worldwide and has led to the quest for safer and more effective topical chemopreventive agents. In this study, the in vivo efficacy of a hydrogel formulation containing kaempferol and ferulic acid-loaded nanoparticles was evaluated for the management of DMBA-croton oil-induced skin cancer in Swiss albino mice. Methods: Drug-loaded nanoparticles prepared via nanoprecipitation were incorporated into hyaluronic acid to obtain single-drug (FAPG, KMPG) and dual-drug-loaded (FKMG) hydrogel formulations. Skin tumors were induced via DMBA as an initiator followed by croton oil as a promoter, with tumor onset observed after a similar latency period of approximately 5–6 weeks in all carcinogen-exposed groups. Treatment was initiated after week 6 and continued until week 16. Results: The gel formulation had a skin-compatible pH and the desired rheological and spreadability properties. The dual drug-loaded hydrogel formulation had a more controlled and prolonged release profile. Compared with the negative and vehicle control groups, the FKMG-treated group presented a marked reduction in tumor incidence and tumor burden, along with improved body weight gain. Biochemical analysis revealed the restoration of antioxidant and enzyme activity in treated animals, particularly in animals treated with FKMG. Histopathological examination revealed near-normal skin architecture in FKMG-treated mice, indicating strong protective effects. Additionally, significant downregulation of TNF-α and IL-6 suggested effective suppression of tumor-promoting inflammatory pathways. Conclusions: Overall, the FKMG formulation exhibited superior chemopreventive efficacy compared with the FAPG and KMPG treatments, highlighting its potential as a promising topical therapeutic strategy against chemically induced skin carcinogenesis. Full article

Oleanolic acid is a naturally occurring pentacyclic triterpenoid with broad preclinical promise in inflammation, oxidative stress, liver injury, metabolic disorders, cancer-related models, skin disease, and wound repair. Its further development, however, is constrained by poor aqueous solubility, low and variable bioavailability, limited barrier transport, crystallinity, and strong dependence of biological response on the formulation used. These properties make oleanolic acid a useful example of a hydrophobic natural compound whose pharmacological performance is inseparable from delivery design. This review examines polymeric nanocarriers and polymer-assisted delivery platforms developed for oleanolic acid delivery. Polymeric nanocarriers discussed in the review include biodegradable PLA/PLGA nanoparticles, PEGylated polymeric nanoparticles, polymeric micelles, nanogels, hyaluronic-acid-based nanoprodrugs, and selected polymer-assisted hybrid nanostructures. Hydrogels, polymeric fiber membranes, local depots, and microneedle systems are included as route-enabling delivery platforms when the polymeric matrix directly contributes to OA incorporation, carrier stabilization, local retention, barrier bypass, or release control. Non-polymeric delivery systems are discussed only as comparators or when their performance depends on integration with a polymeric component. Rather than treating these carriers only as solubility enhancers, the review evaluates how polymer composition, carrier architecture, drug physical state, release behavior, and route of administration affect oleanolic acid exposure. Particular attention is given to controlled release, local retention, disease-oriented delivery, and critical quality attributes such as particle size, loading, encapsulation efficiency, solid-state form, stability, residual solvent, sterility, and batch-to-batch reproducibility. Representative quantitative data on carrier size, drug loading, encapsulation efficiency, release, stability, tissue exposure, and biological outcomes are compared to illustrate both formulation-specific performance and the substantial methodological heterogeneity of the available studies. The available evidence indicates that increased apparent solubility, increased biological exposure, and improved therapeutic response should be treated as related but distinct outcomes. The most realistic near-term opportunities may lie in local and tissue-targeted applications, including inflammatory skin disease, wound healing, dermal delivery, and osteoarthritis, where sustained target-site exposure may be more relevant than systemic bioavailability. Future progress will depend on demonstrating that each formulation provides reproducible, safe, and route-appropriate OA exposure, together with a measurable advantage over simpler delivery approaches. Full article