Search Results (318)

Zoledronic compounds are widely used as antiresorptive and antitumor agents to prevent bone loss and treat multiple myeloma; however, their pharmacokinetic limitations motivate the search for alternative delivery systems capable of improving their controlled release and bioavailability. In this work, we investigate the stability, structural behavior, and adsorption properties of zoledronic acid (ZOL) and its Ca²⁺ and Zn²⁺ salts confined within the interlayer space of the smectite clay mineral montmorillonite by combining empirical force field (FF), density functional theory (DFT), and molecular dynamics (MD) simulations. The main objective of this study is to evaluate the suitability of montmorillonite as a potential drug delivery system (DDS). Specifically, crystal polymorph structures of zoledronic acid [1-(2-hydroxy-2-phosphonate-2-phosphonoethyl)-1H-imidazol-3-ium)] (ZOL) and its Ca²⁺ and Zn²⁺ salts were analyzed. Our calculated crystal structures obtained by both methods (FF and DFT) agree well with the known experimental data. Furthermore, the intercalation of ZOL into the confined interlayer space of montmorillonite is energetically favorable. Several interlayer cations (Na⁺, Ca²⁺, and Zn²⁺) were also evaluated. MD simulations showed that ZOL adopts stable confined configurations within the interlayer space of montmorillonite, exhibiting small torsions of the imidazole group. Additionally, the desorption of ZOL in a modelized acidic medium is energetically favorable. Our calculations predict that this clay mineral holds strong potential for the controlled delivery of zoledronic compounds. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating frequent administration. In this study, we developed an eyelid-applied drug delivery system (DDS) based on troxipide (TRO) nanoparticle formulation (TRO-NP@EG) to achieve sustained ocular surface delivery. Methods: TRO nanosuspensions were prepared by wet bead milling and incorporated into a Carbopol-based gel. Particle size, dispersion stability, and uniformity were evaluated, and in vitro drug release studies was compared with that of TRO-MP@EG. In vivo drug transfer into tear fluid was assessed in rabbits following eyelid application, and therapeutic efficacy was evaluated in an N-acetylcysteine-induced dry eye model. Results: TRO nanosuspensions had a mean particle size of approximately 118 nm. TRO-NP@EG exhibited superior dispersion stability and uniformity and achieved 2.5-fold higher drug release than TRO-MP@EG, while the nanoparticles remained in solid form. In vivo studies in rabbits, TRO-NP@EG significantly enhanced drug transfer into tear fluid, primarily via the meibum pathway. Furthermore, TRO-NP@EG significantly improved mucin levels, tear secretion, and tear film stability compared with TRO-MP@EG in an N-acetylcysteine-induced dry eye model. Conclusions: These findings suggest that eyelid application of nanoparticle-based formulations enables efficient and sustained drug delivery to the ocular surface via the meibomian glands. Therefore, TRO-NP@EG represents a promising therapeutic strategy for DED, providing enhanced efficacy and a novel route of administration for ophthalmic DDSs. Full article

Drug delivery systems (DDS) may improve the therapeutic performance of chemotherapy in lung cancer, but their preclinical efficacy has not been quantitatively synthesized. We conducted a systematic review and meta-analysis of controlled in vivo mouse studies evaluating DDS-based chemotherapeutic formulations for lung cancer. Databases were searched from inception to 15 February 2025, and methodological quality was assessed using the SYRCLE risk-of-bias tool. Thirty studies comprising 47 experiments were included. Compared with corresponding free-drug treatments, DDS-based chemotherapy significantly reduced tumor volume (WMD −310.67 mm³; 95% CI: −375.51 to −245.83; p < 0.001), although substantial heterogeneity was observed. Both targeted and non-targeted DDS were associated with tumor growth inhibition, and targeted formulations showed a larger average reduction; however, this finding should be interpreted in light of differences in formulation properties, tumor models, and treatment protocols. Nanoparticle, liposomal, and micellar platforms all demonstrated significant antitumor effects, while combination DDS and docetaxel- or cisplatin-based systems showed large effects in subgroup analyses with variable sample sizes. These findings support the continued development of DDS-based chemotherapy for lung cancer, but standardized reporting of nanocarrier characterization, pharmacokinetics, biodistribution, toxicity, and rigorous animal-study design is required to improve reproducibility and translational relevance. Full article

The growing demand for sustainable, biocompatible, and non-toxic biomaterials has driven significant advancements in biobased gels for biomedical applications. Among these, cellulose—the most abundant renewable biopolymer—presents an ideal platform due to its inherent hydrophilicity, structural tunability, and biodegradability. This review reports the recent advancements in the processing and engineering of cellulose-based hydrogels for drug delivery systems. We systematically explore the primary synthesis routes, including physical, chemical, and hybrid cross-linking strategies. Special emphasis is placed on chemical modifications (e.g., sulfation, carboxylation, etherification, and polymer grafting) that allow precise tuning of the gel’s mechanical strength, swelling kinetics, and stimuli-responsiveness (such as pH, temperature, or enzyme sensitivity). Furthermore, the review highlights essential characterization techniques—spanning structural, morphological, and rheological evaluations—used to relate cross-link density to the water-holding capacity and network homogeneity. By leveraging their highly hydrated and porous 3D architectures, these modified cellulosic networks demonstrate exceptional efficiency in drug loading, controlled release, and targeted localized therapy. Finally, we discuss current challenges, including industrial scalability and mechanical stability, and provide future perspectives on integrating nanoparticles and bioactive moieties to develop “smart” drug-eluting matrices and wound care dressings. Ultimately, this review underscores the immense potential of cellulose-based gels in advancing both clinical outcomes and circular economy goals. Full article

Cancers still remain one of the most significant challenges in medicine or pharmacy, accounting for nearly 10 million deaths annually and imposing a substantial socioeconomic burden worldwide. Although chemotherapy continues to play a central role in the treatment of many tumors, conventional anticancer therapies are frequently associated with poor selectivity, systemic toxicity, multidrug resistance, and unfavorable pharmacokinetic profiles. Paclitaxel (PTX), one of the most widely used antineoplastic agents, demonstrates remarkable clinical efficacy against breast, ovarian, lung, pancreatic, and several other malignancies. Nevertheless, its clinical application remains limited by poor aqueous solubility, non-specific biodistribution, dose-limiting toxicities, and the development of resistance mechanisms. Nanotechnology-based anticancer drug delivery systems have emerged as a promising strategy to address these limitations. Among them, polymeric nanosystems have attracted particular attention owing to their physicochemical properties, biocompatibility, controlled drug-release capabilities, and potential for tumor-targeted delivery. Natural, semi-synthetic, and synthetic polymers are extensively investigated as carriers for PTX, leading to the development of nanoparticles, micelles, nanogels, nanofibers, dendritic systems, and hybrid nanoplatforms. Nanosystems demonstrate enhanced therapeutic efficacy, reduced systemic toxicity, prolonged circulation times, and improved tumor accumulation in preclinical models. Despite encouraging laboratory results, the clinical translation of polymeric PTX nanocarriers (NCs) remains limited. Numerous barriers, including tumor heterogeneity, variability of the enhanced permeability and retention (EPR) effect, manufacturing complexity, regulatory challenges, scale-up difficulties, and discrepancies between animal models and human cancers, continue to hinder successful commercialization and widespread clinical adoption. This review critically discusses the current state of polymeric drug delivery systems (DDSs) that contain PTX, as well as the advantages and limitations of synthetic, natural, and semi-synthetic polymers used in DDS technologies. Furthermore, translational challenges and future perspectives of PTX-based DDSs were analyzed. Full article

Neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, and Huntington’s disease are progressive and currently incurable conditions characterized by the deterioration of neuronal structure and function. Its incidence is increasing, primarily driven by global aging, and it represents a significant public health concern. Traditional therapies offer only symptomatic relief and are unable to halt or reverse the underlying neurodegenerative processes. One of the key challenges in developing effective treatments is the presence of biological barriers, such as the blood–brain barrier (BBB), which limits drug delivery to the central nervous system (CNS), namely the brain. Nanotechnology has emerged as a promising tool to overcome these obstacles. Nanoparticles (NPs), due to their small size, biocompatibility, and versatility, can be engineered to cross the BBB, protect therapeutic agents from degradation, and deliver them precisely to target sites in the brain. This work explores the current advances in lipid and polymeric-based nanoparticle (LNPs and PNPs, respectively) drug delivery systems (DDS) and their application in preclinical studies for the treatment of the NDs previously mentioned. The presented studies suggest that this strategy holds great potential, offering new perspectives and emerging strategies to improve therapeutic outcomes for NDs, and promote neuroprotection of the brain. Full article

Background/Objectives: Modern dentistry increasingly requires biomaterials that not only replace damaged tissues but also actively regulate healing processes, modulate inflammation, and provide controlled delivery of therapeutic agents under the complex physicochemical conditions of the oral cavity. This review aims to analyze the potential of PCHs, particularly methacryloyl gelatin (GelMA), as multifunctional platforms for drug delivery in dental applications. Methods: This review provides a structured narrative synthesis of the literature, focusing on the physicochemical, biological, and translational aspects of photocrosslinkable hydrogels in dentistry. Special attention was given to the key functional requirements for hydrogels used in dentistry, including adhesion in a wet environment, antimicrobial properties, and the ability to provide sustained and localized release of active compounds. Natural, synthetic, and semi-synthetic polymers were comparatively evaluated to justify the selection of GelMA as a leading platform due to its tunable mechanical properties, biocompatibility, and photopolymerization capacity. The review also analyzes mechanisms of drug release activation and provides a comparative assessment of commonly used photoinitiators, including Irgacure 2959, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and camphorquinone, with emphasis on their cytocompatibility with oral tissues. Results: Applications of these hydrogels in endodontics, periodontology, peri-implantitis therapy, and regeneration of bone and dental pulp are summarized. Conclusions: Overall, photocrosslinkable GelMA-based hydrogels (PC-GelMA) represent promising multifunctional platforms for localized drug delivery and regenerative strategies in modern dentistry. Full article

Traditional pharmacotherapy is often constrained by suboptimal bioavailability and systemic toxicity. Biomolecularly inspired nano-drug delivery systems (nano-DDS) have emerged as precise platforms to overcome these barriers by orchestrating molecular interactions at the bio-nano interface. This review systematically evaluates the molecular recognition mechanisms and biochemical principles governing nano-DDS performance. We systematically evaluate how passive targeting relies on the EPR effect—dictated by the nanocarrier’s physicochemical properties—and how active targeting exploits ligand-receptor affinity to enhance cellular uptake. Special emphasis is placed on bioresponsive strategies that utilize pathological cues—such as pH gradients, redox potential, and enzymatic activity—for intelligent, on-demand drug release. Furthermore, we discuss structure-function relationships in lipid, polymeric, and biologically derived systems, highlighting their roles in modulating therapeutic signaling in oncology and inflammatory diseases. Finally, translational hurdles and emerging AI-driven molecular design strategies are critically examined. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by progressive dementia, constituting one of the leading causes of global mortality. Although the current treatments help attenuate the symptoms associated with AD, they are unable to stop the long-term progression of the disease, and consequently, no cure exists. One of the main reasons for the lack of cure and, therefore, one of the biggest challenges in its treatment, is the blood–brain barrier (BBB). This protective barrier limits the entry of foreign substances, including drugs, into the central nervous system. Different types of engineered nanoparticles (NPs) have been demonstrated to be able to penetrate this barrier and serve as efficient drug delivery systems (DDS) into the brain, making them a promising solution for future therapeutic development. Therefore, the purpose of this paper is to provide valuable insights into challenges faced by DDS in treating AD, highlight the nanotechnology-based approach, and discuss the advances in strategies being employed to enhance the crossing of NPs through the BBB. Furthermore, some up-to-date NP systems are presented, along with the latest therapeutic agents targeting AD, and finally, it underscores innovative approaches under investigation. Ultimately, the barriers hindering the clinical translation of NP-based strategies into human patients are discussed. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

Liposomes, spherical bilayer lipid-containing vesicles, are promising nanocarriers used for constructing drug delivery systems (DDS). Various strategies can be employed to loosen or break the liposome and release drugs as the tumor cells-targeting DDS made of liposomes reach the targeted sites. One of the most commonly used strategies is to heat the liposomal DDS by letting the gold nanoparticles or other light-absorbing substances that partition in various portions (inner water core, lipid bilayer or outside) of the liposome absorb light irradiation. Then, which portion can lead to the largest liposome structure change due to the same temperature variation? The answer is essential to aid the design of liposomal DDS; thus, wet lab experiments were carried out. However, even though irradiation-absorbing substances in different portions were irradiated for the same time and with the same irradiation intensity, it was impossible to ensure the three portions have the same temperature increase in the experiments. Furthermore, it is impossible to learn the related micromechanism and molecular-level details of the effects of temperature changes on the liposome structure with experimental methods. The molecular dynamics (MD) method is extensively employed by researchers to obtain in-depth molecular-level insights. Most researchers tend to simulate only a planar lipid bilayer structure, but Amărandi et al. demonstrated that such simplification strategy may give wrong simulation results contrary to the experimental results. Though Jämbeck et al. and Zhu et al. established whole spherical liposome systems with a diameter of about a dozen nanometers and simulated the systems with MD simulations, they did not simulate temperature-relevant properties of the liposome. Therefore, currently there is a lack of research on simulating the structure change in a whole spherical liposome due to temperature variations. So, we established the whole spherical structure of the liposome, simulated how it changes with temperatures and obtained molecular-level research results. It is observed that the temperature increase in the lipid bilayer causes the largest increase in lipid strand sway amplitude, the largest changes in lipid positions, the largest decrease in the distribution density of lipids and water around a lipid and the largest decrease in the interactions between lipids and lipids and between lipids and water, leading to the largest change in the liposome structure. We also studied how the degree of lipid tail unsaturation affects liposome structure changes with temperatures. Due to the C3 kinks in the unsaturated lipid tails, the distribution density of unsaturated lipids is not as high as saturate ones, leading to smaller attraction interactions and consequently larger liposome structure change with temperature. The obtained results are useful for the liposomal DDS design for the purpose of improving DDS performances and delivery outcomes. Full article

Alzheimer’s disease (AD) remains a major unmet medical challenge due to its complex pathology, high interpatient heterogeneity and frequent association with systemic comorbidities. Conventional pharmacotherapy is limited by poor blood–brain barrier permeability, off-target effects and reduced efficacy in polymedicated elderly populations. Smart drug-delivery systems (DDS), particularly nanotechnology-based platforms, have emerged as promising strategies to enhance brain targeting, optimize controlled drug release and mitigate systemic toxicity. This review examines recent advances in intelligent DDS for AD, with a focus on nanocarriers designed to modulate amyloid aggregation, neuroinflammation, oxidative stress and cholinergic dysfunction. Special attention is given to the impact of the most common comorbid conditions on DDS pharmacokinetics, safety and clinical performance. Furthermore, the challenges associated with clinical translation, such as long-term safety, immunogenicity, manufacturing scalability and regulatory harmonization, are critically discussed. In this context, versatile controlled release platforms that integrate rational design, predictive modeling and Quality by Design-driven manufacturing are highlighted as key enablers of translational success. By bridging intelligent formulation design with scalable production and regulatory readiness, advanced controlled release systems offer a pathway toward precision and patient-centered therapies. Such platforms hold significant potential to accelerate the safe integration of smart DDS into Alzheimer’s disease management and broader neurotherapeutic applications. Full article

Photodynamic therapy (PDT) is a promising localized strategy for the treatment of cervical cancer, ranking as the fourth most common cancer among women worldwide. The integration of photosensitizers (PSs) in localized drug delivery systems (DDSs), particularly in electrospun nanofibers, holds tremendous potential to overcome the drawbacks of their systemic administration. Exploring multilayer fibrous architectures provides a versatile therapeutic platform to design the next generation of localized DDS. In this work, localized implants for cancer treatment using PDT were developed using polyhydroxyalkanoate (PHA), chitosan (CS) and polyethylene oxide (PEO) as biopolymers and a porphyrin (Por) as PS, following two approaches: blended PHA/Por electrospun microfibers and multilayered membranes (PHA–Por/CS/PEO) produced by sequential electrospinning. The synthesized Por displayed higher cytotoxicity in light compared to dark against tumor cells. All the developed membranes were characterized regarding their morphology, wettability, absorption and fluorescence properties. PHA–Por membranes exhibited overall uniform fibrous morphologies with successful Por incorporation. Nonetheless, they presented a highly hydrophobic surface, compromising the Por release and cell–material interactions. In contrast, multilayer PHA–Por/CS/PEO membranes demonstrated enhanced hydrophilicity and enabled sustained Por release. Upon light irradiation, these membranes induced a significantly greater inhibition of HeLa cell proliferation (29.61%) compared to dark conditions (6.21%), confirming their photodynamic activity. Full article

Gold nanorods (AuNRs) were synthesized and optimized with the aim of obtaining strongly hydrophilic nanomaterials, suitable as a drug delivery system (DDS) for copper-based drugs. After careful purification, AuNRs were characterized by ultraviolet–visible–near-infrared spectroscopy (UV–Vis–NIR), showing two typical localized surface plasmon resonance (LSPR) bands in the range 550–750 nm. Fourier Transform Infrared (FT-IR) and high-resolution X-ray photoelectron (HR-XPS) spectroscopies verified the surface functionalization. Transmission electron microscopy (TEM) showed AuNRs with regular shape and size, with an aspect ratio (AR) of 2.6. Dynamic Light Scattering (DLS) measurements confirmed the size and the stability in water for up to 3 months. The AuNRs were conjugated with copper(I) drugs, i.e., [Cu(PTA)₄]BF₄ (PTA = 1,3,5-triaza-7-phosphadamantane). The drug loading procedures and efficiency were optimized, and the best loading was η (%) = 50 ± 7%. The non-covalent interactions of the Cu(I) complex with the AuNRs were studied by means of UV–Vis–NIR, ζ-potential, HR-TEM, FT-IR, synchrotron radiation-induced X-ray photoelectron (SR-XPS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy measurements. The MTT assay performed on Vero E6 cells showed that AuNRs and AuNR-Cu(I) conjugates had no significant effect on cell viability, being biocompatible, causing a reduction in cell viability only after prolonged exposure. Full article

Tissue regeneration is essential for wound healing, organ function restoration, and overall patient recovery. Its success significantly impacts medical procedures in fields like internal medicine and orthopedics, enhancing patient quality of life. Recent advances in regenerative medicine, particularly the combination of advanced drug delivery systems (DDS) and bioengineering, have enabled customized methods to improve tissue regeneration outcomes. However, conventional tissue engineering techniques have drawbacks, often using static scaffolds that lack the dynamic properties of real tissues, leading to subpar healing outcomes. The use of 3D printing and other advanced scaffolding techniques allows for the creation of bio functional scaffolds that deliver bioactive molecules at precise locations and times. The optimal integration of biological systems with enhanced material properties for personalized treatment options remains unclear. There is a need for more research into the complex interactions between cellular biology, drug delivery, and material technology to improve tissue regeneration. Despite progress in developing bioactive scaffolds and localized drug delivery methods, the interactions among different scaffold materials, bioactive agents, and cellular behaviors within the regenerative ecosystem are not fully understood. While there is extensive research on 3D-printed scaffolds in tissue engineering, there is a lack of studies integrating bio printing with in vivo biological reactions in real time. Limited research on the dynamic integration of patient-specific parameters in regeneration methods highlights the need for customized approaches that consider individual physiological differences and the complex biological environment at injury sites. Additionally, challenges arise when translating laboratory results into effective therapeutic applications, underscoring the necessity for interdisciplinary collaboration and innovative design approaches that align advanced material properties with biological needs. Full article