Search Results (287)

Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using ¹H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC₅₀ values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential. Full article

Background: This study developed and characterized a novel drug delivery system (DDS) for potential use in oral surgery, combining poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with chlorhexidine (MS-CHX) and a polyethylene glycol (PEG)-based hydrogel containing dexketoprofen (HG-DXT). Methods: MS-CHX was synthesized using a double emulsion evaporation method, while HG-DXT was formulated from a PEG blend. The components were combined in a 2:1 ratio to create the MS-CHX/HG-DXT DDS. Characterization techniques included differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDS). Antibacterial activity was evaluated using disk diffusion assays against E. faecalis, E. coli, S. aureus, and C. albicans. Biocompatibility was assessed with MTS, and drug release was measured via high-performance liquid chromatography (HPLC) in vitro. Results: CHX-loaded microspheres showed spherical morphology, stability above 37 °C, and antimicrobial efficacy. HG-DXT demonstrated good biocompatibility (80% of cell viability) and stable physicochemical properties (stability at 50-day storage). The DDS exhibited a biphasic release: an initial burst of dexketoprofen for analgesia, followed by sustained release of chlorhexidine for antimicrobial protection. Conclusions: This novel dual-action DDS showed promising characteristics and a favorable release profile, supporting its potential as a therapeutic alternative for post-operative pain and infection control in oral surgical procedures. Full article

Periodontitis is a highly prevalent, irreversible inflammatory disease characterized by the destruction of tooth-supporting tissues, eventually leading to tooth loss. Conventional treatment involves the mechanical removal of the subgingival biofilm, which is a major cause of gingival inflammation. However, the inaccessibility of deep-seated polymicrobial biofilms limits its effectiveness. Despite the adjunct use of systemic antimicrobials, their low site-specific bioavailability and systemic side effects remain concerns. Local drug administration offers a targeted alternative. However, the dynamic oral environment, which is characterized by continuous salivary and gingival crevicular fluid flow, poses challenges in maintaining therapeutic drug levels. Drug delivery systems (DDSs) provide technical solutions to overcome these limitations. With advancements in materials science and nanotechnology, diverse local DDS (LDDS) formulations tailored for periodontal applications have been developed. While traditionally focused on infection control, the application of LDDSs has expanded beyond antimicrobial therapy. Increasing attention has been paid to LDDS-based regenerative strategies, which aim to overcome the limitations of conventional regenerative therapies. This review aims to provide a comprehensive overview of the current and emerging DDS strategies in periodontal therapy, focusing on their applications in infection management and bone regeneration and discussing their limitations and prospects for clinical translation. Full article

Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a naturally occurring biopolymer belonging to the polyhydroxyalkanoate (PHA) family. Due to its excellent properties (biocompatible, biodegradable, and non-toxic), this biopolymer is presented as a very suitable option for use in regenerative therapy as a drug delivery system (DDS). The protein encapsulated in this study is transforming growth factor β3 (TGF-β3), which plays a key role in the chondrogenic differentiation of mesenchymal stem cells (MSCs). The main objective of this work is to evaluate the efficacy of PHBV nanoparticles (NPs) produced from a dairy by-product (whey) as a DDS of TGF-β3 for cartilage regeneration and extracellular matrix (ECM) synthesis and to reduce the complications associated with multiple high doses of TGF-β3 in its free form. For this purpose, biopolymer cytotoxicity, factor release, cell viability, cell proliferation, and differentiation were analyzed. The results showed that the biomaterial purified with chloroform and ethanol, either by single or double precipitation, was not toxic to cells. A sustained release profile was observed, reaching its maximum around day 4. The TGF-β3 NPs promoted the differentiation of MSCs into chondrocytes and the formation of ECM. In conclusion, PHBV demonstrated its potential as an optimal material for DDSs in cartilage regenerative therapy, effectively addressing the key challenge of the need for a single delivery method to reduce complications associated with multiple high doses of TGF-β3. Full article

Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing the dosage necessary. A biodegradable polyester polycaprolactone (PCL)-based DDS was thus produced, containing various clinically relevant drugs. It was shown that the incorporation of four distinct antibiotic classes (amoxicillin, doxycycline, metronidazole and rifampicin), with very high mass fractions ranging up to 20 wt%, was feasible within the PCL matrix. This DDS showed the capacity for effective and sustained release. The release kinetics over 14 days were proven, showing a significant decrease in cytotoxicity with smooth muscle cells as well as an antibacterial effect on (1) aerobic, (2) anaerobic, (3) Gram-positive and (4) Gram-negative pathogens in vitro. The DDS demonstrated a markedly diminished cytotoxic impact owing to sustained release in comparison to pure antibiotics, while simultaneously maintaining their antibacterial efficacy. In conclusion, DDSs are a more tolerable form of antibiotics administration due to the hydrophobic PCL matrix causing a slower diffusion-controlled release, proven as a release mechanism via the Peppa–Sahlin model. Full article

Bone metastases are a prevalent and debilitating consequence of various cancers, including breast and prostate carcinomas, which significantly compromise patient quality of life due to pain, fractures, and other skeletal-related events (SREs). This review examines the pathophysiology of bone metastases, emphasizing the role of the bone microenvironment in tumor progression through mechanisms such as osteotropism and the dysregulated bone remodeling cycle. The primary focus is on the emerging nano-drug delivery systems (DDS) designed to target the bone microenvironment and improve the therapeutic index of anticancer agents. Current treatments, mainly comprising bisphosphonates and radiotherapy, provide palliative benefits but often have limited efficacy and significant side effects. Innovative strategies, such as bisphosphonate-conjugated nanoparticles and targeted therapies that utilize the unique bone marrow niche, are explored for their potential to enhance drug accumulation at metastatic sites while minimizing systemic toxicity. These approaches include the use of liposomes, polymeric nanoparticles, and inorganic nanoparticles, which can be functionalized to exploit the biological barriers within the bone microenvironment. This review also discusses the challenges and future directions for nano-DDS in clinical settings, emphasizing the need for multidisciplinary research to effectively integrate these technologies into standard care protocols. Full article

Background/Objectives: Anthocyanins (ACNs) derived from mulberry (Morus alba L.) exhibit potent antioxidant and anti-inflammatory activities. However, their low stability and bioavailability in physiological environments limit their therapeutic potential. This study aimed to enhance the stability and controlled release ACNs using a hot-melt extrusion drug delivery system (HME-DDS) formulation, HME-MUL-F2, and evaluate its effects on gut barrier function and microbiota composition in a DSS-induced colitis model. Methods: The anthocyanin content of HME-MUL-F2 was quantified and compared with that of raw mulberry extract. The formulation’s protective effects were assessed in Caco-2 and RAW 264.7 cells, confirming its biocompatibility and anti-inflammatory properties. The therapeutic efficacy was further evaluated in a dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) model, focusing on gut barrier integrity, inflammatory cytokine modulation, and gut microbiota composition. Results: HME-MUL-F2 significantly improved gut barrier function by upregulating tight junction proteins and reducing inflammatory cytokine levels in the colitis model. Moreover, the formulation modulated gut microbiota composition, promoting beneficial bacteria while suppressing pathogenic strains. HME-MUL-F2 administration led to a significant increase in the Bacteroidetes-to-Firmicutes ratio, which is associated with improved gut health. These results indicate that HME-MUL-F2 significantly enhances anthocyanin bioavailability, leading to improved gut health and potential therapeutic applications for inflammatory conditions. Conclusions: This study highlights the potential of HME technology for improving the stability, bioavailability, and therapeutic efficacy of anthocyanins. HME-MUL-F2 is a sustained-release formulation that enhances gut barrier function and modulates intestinal microbial balance in a DSS-induced inflammatory bowel disease model. These findings strongly suggest that the observed therapeutic effects of HME-MUL-F2 are primarily due to enhanced anthocyanin bioavailability and targeted delivery to the colon, although further clinical studies will provide more definitive confirmation. Full article

With the unprecedented progress of biomedical nanotechnology in the past few decades, traditional drug delivery systems (DDSs) have been incorporated into intelligent DDSs with stimulus responsive characteristics. Graphene oxide (GO) and Chitosan (CS) have excellent physical, chemical, mechanical, and optical properties, and their synergistic effects have attracted widespread attention in the biomedical field. In this review, we focus on the physicochemical characteristics of GO, CS, and GO/CS composites, as well as the research progress of DDS types based on GO/CS. Full article

Biodegradable polyesters have been researched intensively over the last two decades because of their biodegradability and superb physical properties. However, the use of linear biodegradable polyesters, for the preparation of drug delivery systems (DDS), is hampered by several limitations. In view of this, scientific attention has been shifted to the employment of branched-chain (co-)polymers. In this context, we present herein the development of new melatonin (MLT) tablet formulations, using novel branched polylactide (PLA)-based copolymers of different architectures. Specifically, three PLA-polyol branched polyesters, namely, a three-arm copolymer based on glycerol (PLA-glycerol), a four-arm copolymer based on pentaerythritol (PLA-pentaerythritol), and a six-arm copolymer based on sorbitol (PLA-sorbitol), were utilized. The presence of these polyesters in the formulations was found to be crucial, as the sought MLT release, regarding its use in confronting sleep onset and/or sleep maintenance dysfunctions, was achieved. The copresence of the other excipients in the matrix tablets (lactose monohydrate, hydroxypropylmethylcellulose, microcrystalline cellulose, and sodium alginate) led to a concentration-dependent synergistic effect on the MLT release. To the best of our knowledge, this is the first investigation with these specific polymeric materials, concerning MLT modified release from matrix tablets. Full article

Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments. Full article

In the 21st century, thanks to advances in biotechnology and developing pharmaceutical technology, significant progress is being made in effective drug design. Drug targeting aims to ensure that the drug acts only in the pathological area; it is defined as the ability to accumulate selectively and quantitatively in the target tissue or organ, regardless of the chemical structure of the active drug substance and the method of administration. With drug targeting, conventional, biotechnological and gene-derived drugs target the body’s organs, tissues, and cells that can be selectively transported to specific regions. These systems serve as drug carriers and regulate the timing of release. Despite having many advantageous features, these systems have limitations in thoroughly treating complex diseases such as cancer. Therefore, combining these systems with nanoparticle technologies is imperative to treat cancer at both local and systemic levels effectively. The nanocarrier-based drug delivery method involves encapsulating target-specific drug molecules into polymeric or vesicular systems. Various drug delivery systems (DDS) were investigated and discussed in this review article. The first part discussed active and passive delivery systems, hydrogels, thermoplastics, microdevices and transdermal-based drug delivery systems. The second part discussed drug carrier systems in nanobiotechnology (carbon nanotubes, nanoparticles, coated, pegylated, solid lipid nanoparticles and smart polymeric nanogels). In the third part, drug targeting advantages were discussed, and finally, market research of commercial drugs used in cancer nanotechnological approaches was included. Full article

Background/Objectives: This study aimed to design and evaluate Chol-PEG₂₀₀₀ micelles and Chol-PEG₅₀₀ vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer’s disease (AD). Methods: The physical properties of Chol-PEG assemblies were characterized using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). Inhibitory effects on Aβ aggregation were assessed via thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, and native polyacrylamide gel electrophoresis (native-PAGE). Results: Chol-PEG₂₀₀₀ micelles and Chol-PEG₅₀₀ vesicles were found to exhibit diameters of 20–30 nm and 70–80 nm, respectively, with neutral surface charges and those physical properties indicated the high affinity for Aβ. At a 10-fold molar ratio, thioflavin T (ThT) assay revealed that Chol-PEG₂₀₀₀ delayed Aβ fibril elongation by 20 hours, while Chol-PEG₅₀₀ delayed it by 40 hours against Aβ peptide. At a 50-fold molar ratio, both Chol-PEG₂₀₀₀ and Chol-PEG₅₀₀ significantly inhibited Aβ aggregation, as indicated by minimal fluorescence intensity increases over 48 hours. CD spectroscopy indicated that Aβ maintained its random coil structure in the presence of Chol-PEG assemblies at a 50-fold molar ratio. Native-PAGE analysis demonstrated a retardation in Aβ migration immediately after mixing with Chol-PEG assemblies, suggesting complex formation. However, this retardation disappeared within 5 min, implying rapid dissociation of the complexes. Conclusions: This study demonstrated that Chol-PEG₅₀₀ vesicles more effectively inhibit Aβ aggregation than Chol-PEG₂₀₀₀ micelles. Chol-PEG assemblies perform as DDS carriers to be capable of inhibiting Aβ aggregation. Chol-PEG assemblies can deliver additional therapeutics targeting other aspects of AD pathology. This dual-function platform shows promise as both a DDS carrier and a therapeutic agent, potentially contributing to a fundamental cure for AD. Full article

Single and dual-drug delivery systems (DDSs) based on linear choline polymers were designed through the controlled polymerization of a pharmaceutically functionalized monomer, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium, with counterions of cloxacillin (TMAMA/CLX), or its copolymerization with [2-(methacryloyloxy)ethyl]trimethylammonium with ampicillin (TMAMA/AMP), providing antibiotic properties. This strategy was effective in attaining well-defined linear copolymers with 38–93 mol. % of TMAMA content, which were regulated by the initial ratio of TMAMA to methyl methacrylate comonomer. The polymer compositions were controlled by the total monomer conversion (40–75%), resulting in a variable degree of polymerization (DP_n = 160–300) and pharmaceutical anion contents (CLX⁻ 51–80% and AMP⁻ 78–87%). In aqueous solution, the polymers formed particles with sizes ranging between 274 and 380 nm for CLX⁻ systems and 288–348 nm for CLX⁻/AMP⁻ systems. In vitro drug release, driven by the exchange of pharmaceutical anions with phosphate ions in phosphate-buffered saline (PBS), imitating a physiological fluid, demonstrated release efficiencies of 58–76% for CLX⁻ (10.5–13.6 µg/mL) in single systems, and 91–100% for CLX⁻ (12.9–15.1 µg/mL) and 97–100% for AMP⁻ (21.1–23.3 µg/mL) in dual systems. Compared to conventional systems delivering antibiotics without a polymer carrier, the choline-based polymer DDS attained satisfactory levels of drug loading content and (co-)release from the polymer carriers, offering a promising alternative for antibiotic delivery. Full article

Background: Supersaturating drug delivery systems (SDDSs) have gained significant attention as a promising strategy to enhance the solubility and bioabsorption of Biopharmaceutics Classification System (BCS) II drugs. To overcome challenges associated with polymer-based amorphous SDDS (aSDDS), coamorphous (CAM) systems have emerged as a viable alternative. Among them, “drug-drug” CAM (ddCAM) systems show considerable potential for combination drug therapy. However, many drugs in their pure amorphous forms are unstable at room temperature (RT), complicating their formation and long-term stability profiles. Consequently, limited knowledge exists regarding the behavior of ddCAMs containing RT-unstable components formed via quench cooling. Methods: In this study, we used naproxen (NAP), a RT-unstable amorphous drug, in combination with felodipine (FEL) or nitrendipine (NTP), two RT-stable amorphous drugs, to create “FEL-NAP” and “NTP-NAP” ddCAM pairs via quench cooling. Our work used a series of methods to perform a detailed analysis on the co-amorphization, dissolution, solubility, and stability profiles of ddCAMs containing RT-unstable drugs, contributing to advancements in co-amorphization techniques for generating SDDS. Results: This study revealed that the co-amorphization and stability profiles of ddCAMs containing RT-unstable components produced via a quench-cooling method were closely related to drug-drug pairing types and ratios. Both quench-cooling and incorporation into coamorphous systems improved the dissolution, solubility, and physical stability of individual APIs. Conclusions: Our findings provide deeper insight into the co-amorphization, dissolution, and stability characteristics of specific drug-drug coamorphous systems FEL-NAP and NTP-NAP, offering valuable guidance for developing new ddCAM coamorphous formulations containing some RT-unstable drugs. Full article

Background/Objectives: Interest in drug delivery systems (DDS) based on inorganic substrates has increased in parallel with the increase in the number of poorly water-soluble drugs. Hydroxyapatite is one of the ideal matrices for DDS due to its biocompatibility, low cost, and ease of preparation. Methods: We propose two doped hydroxyapatites, one with Ba on Ca sites another with Si on P sites, with the aim of improving the dissolution rate of piretanide, a diuretic, poorly water-soluble drug. The hybrids were characterized by different physical–chemical techniques, and their formation was demonstrated by infrared spectroscopy, thermal analysis, and electron microanalysis, as well as by comparing the results with those obtained on physical mixtures of HAPs and properly prepared piretanide. Results: Both the hybrids improved the piretanide dissolution rate compared with the physical mixtures and the drug alone. The dose was completely solubilized from the Si-doped hybrid in about 5 min in the three fluids considered. This remarkable improvement can be explained by an increase in the wettability and solubility of the drug loaded in the drug-carrier systems. Conclusions: Different experimental techniques, in particular spectroscopy and electronic microanalysis, proved the successful loading of piretanide onto doped HAP. Pharmaceutical measurements demonstrated rapid drug release in different fluids simulating gastrointestinal conditions after oral administration. These hybrid systems could be a very promising platform for drug delivery. Full article