Search Results (336)

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

Biocompatible vaterite microspheres, renowned for their porous structure, are promising carriers for magnetic nanoparticles (MNPs) in biomedical applications such as targeted drug delivery and diagnostic imaging. Precise control over the magnetic moment of individual microspheres is crucial for these applications. This study employs widefield quantum diamond microscopy to map the stray magnetic fields of individual vaterite microspheres (3–10 μm) loaded with Fe₃O₄ MNPs of varying sizes (5 nm, 10 nm, and 20 nm). By analyzing over 35 microspheres under a 222 mT external magnetizing field, we measured peak-to-peak stray field amplitudes of 41 ± 1 μT for 5 nm and 10 nm superparamagnetic MNPs, reflecting their comparable magnetic response, and 12 ± 1 μT for 20 nm ferrimagnetic MNPs, due to distinct magnetization behavior. Finite-element simulations confirm variations in MNP distribution and magnetization uniformity within the vaterite matrix, with each microsphere encapsulating thousands of MNPs to generate its magnetization. This high-resolution magnetic imaging approach yields critical insights into MNP-loaded vaterite, enabling optimized synthesis and magnetically controlled systems for precision therapies and diagnostics. Full article

Chronic lung infection is the main predictor of morbidity and mortality in cystic fibrosis (CF), and current pharmacological alternatives are ineffective against Pseudomonas aeruginosa infections. We developed ciprofloxacin (CIP) for inhalation, aiming at improving its solubility through the formation of an amorphous solid dispersion (ASD) using gelatin (GA). CIP and GA were dissolved in varying ratios and then spray-dried, obtaining CIP-GA microspheres in a single step. The dissolution rate, size distribution, morphology, and aerodynamic properties of CIP-GA microspheres were studied, as well as their antimicrobial activity on P. aeruginosa biofilms. Microspheres formulated with a higher GA ratio increased the dissolution of CIP ten-fold at 6 h compared to gelatin-free CIP. Formulations with 75% GA or more could form ASDs and improve CIP’s dissolution rate. CIP-GA microspheres outperformed CIP in eradicating P. aeruginosa biofilm at 24 h. The spray-drying process produced CIP-GA microspheres with good aerodynamic properties, as indicated by a fine particle fraction (FPF) of 67%, a D₅₀ of 3.52 μm, and encapsulation efficiencies above 70%. Overall, this study demonstrates the potential of gelatin to enhance the solubility of poorly soluble drugs by forming ASDs. As an FDA-approved excipient for lung delivery, these findings are valuable for particle engineering and facilitating the rapid translation of technologies to the market. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Background/Objectives: The formulation of microspheres for lipophilic drugs using aqueous methods, such as spray drying, faces significant challenges. The main objective of this study was to evaluate the effect of the process parameters and polymer selection on the production of microspheres by spray drying for a lipophilic drug. Methods: Lipophilic drug-loaded microspheres were developed using various polymers via the aqueous spray drying method. The effects of the factors on the yield percentage and encapsulation efficiency were analyzed. Microspheres preparation included Agave inulin, guar gum, hydroxypropyl methylcellulose, and Eudragit^® S100. A 2³ factorial design was performed, and the parameters were optimized. Results: Inlet temperature, feed flow, and polymer percentage showed a significant effect (p < 0.05) on the yield percentage of guar gum microspheres and encapsulation efficiency of the inulin microspheres. Inulin and guar gum microspheres showed the best yield percentage (75.41%) and encapsulation efficiency (100%), respectively. In addition, guar gum microspheres had the best morphology, and hydroxypropyl methylcellulose microspheres were smaller and had an irregular surface. Eudragit did not maintain its delayed release property due to limitations of the aqueous method; inulin released the drug immediately, and guar gum and hydroxypropyl methylcellulose microspheres prolonged release only by a few additional hours. Conclusions: The experimental design showed that optimizing the parameters (inlet temperature, feed flow, and the type and percentage of polymer) can regulate the microsphere development process to obtain improved product yield and encapsulation efficiency results. Full article

Cellulose nanocrystals possess unique properties such as high surface area and excellent biocompatibility. They can disrupt strong hydrogen bonds and other intermolecular forces that hinder the solubility of certain molecules thus enhancing the solubility of poorly soluble materials. The main challenge in formulating poorly soluble drugs lies in their limited therapeutic efficacy due to inadequate solubility and bioavailability. Therefore, an innovative approach such as using cellulose nanocrystals to enhance the solubility is highly needed. The aim of this research is to study the potential of ramie (Boehmeria nivea L. Gaud) as a source of cellulose nanocrystals in the development of microspheres for the solubility enhancement of poorly soluble drugs. Nanocrystalline cellulose was isolated from the ramie (Boehmeria nivea L. Gaud) by optimizing hydrolysis conditions with varying acid concentrations and reaction times. Characterizations were performed by measuring particle size, pH, and sulfate content, followed by morphological study by SEM, functional group analysis, and thermal analysis. The use of sulfuric acid in the hydrolysis process of flax cellulose at 45 °C, as the type of acid that gives the best results, at 50% acid concentration for 60 min produces cellulose nanocrystallines with a particle size of 120 nm, sulfate concentration density of 133.09 mmol/kg, crystallinity of 96.2%, and a yield of 63.24 ± 8.72%. Furosemide was used as the poorly soluble drug model and its solubility enhancement in the form of furosemide/RNCC microspheres was evaluated through saturated solubility testing and in vitro dissolution. This study demonstrated that RNCC could improve the solubility of furosemide, which contributes to developing sustainable drug formulations and eco-friendly delivery systems for poorly soluble drugs. 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

If a method for developing organic polymer/apatite core–shell microspheres encapsulating organic polymer microspheres with apatite shells can be constructed, it is possible to establish a fundamental methodology to fabricate apatite capsules for drug delivery carriers. In this study, polystyrene (PS) microspheres were used as model substances in organic polymer microspheres, and the effects of the surface functional groups on the PS microspheres on the amount of Ca²⁺ ions introduced onto the PS microspheres were investigated. The PS/apatite core–shell microspheres were prepared by immersing Ca²⁺-incorporated PS microspheres in a reaction solution containing Ca²⁺, HPO₄²⁻, and Mg²⁺ to coat the surface of PS microspheres with apatite. Particle characterization of the prepared PS/apatite core–shell microspheres was performed, and the relationships among the surface functional groups, surface potential, Ca²⁺ adsorption, and apatite shell formation in the aqueous solution on the PS microspheres were investigated. Full article

Promethazine hydrochloride (PMH) is a first-generation antipsychotic drug created from phenothiazine derivatives that is widely employed to treat psychiatric disorders in human healthcare systems. However, an overdose or long-term intake of PMH can lead to severe health issues in humans. Hence, establishing a sensitive, accurate, and efficient detection approach to detect PMH in human samples is imperative. In this study, we designed orthorhombic copper molybdate microspheres decorated on reduced graphene oxide (Cu₃Mo₂O₉/RGO) composite via the effective one-pot hydrothermal method. The structural and morphological features of the designed hybrid were studied using various spectroscopic methods. Subsequently, the electrochemical activity of the composite-modified screen-printed carbon electrode (Cu₃Mo₂O₉/RGO/SPCE) was assessed by employing voltammetric methods for PMH sensing. Owing to the uniform composition and structural benefits, the combination of Cu₃Mo₂O₉ and RGO has not only improved electrochemical properties but also enhanced the electron transport between PMH and Cu₃Mo₂O₉/RGO. As a result, the Cu₃Mo₂O₉/RGO/SPCE exhibited a broad linear range of 0.4–420.8 µM with a low limit of detection (LoD) of 0.015 µM, highlighting excellent electrocatalytic performance to PMH. It also demonstrated good cyclic stability, reproducibility, and selectivity in the presence of chlorpromazine and biological and metal compounds. Furthermore, the Cu₃Mo₂O₉/RGO/SPCE sensor displayed satisfactory recoveries for real-time monitoring of PMH in human urine and serum samples. This study delivers a promising electrochemical sensor for the efficient analysis of antipsychotic drug molecules. Full article

Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared by incorporating chitosan either by mixing once or through a sequential coating strategy. By adjusting the loading procedure, the DEE increased from 58% to 99%. The composite microsphere effectively controlled the total drug release duration, extending it from one month to over 5 months. Moreover, the MTT assay demonstrated that all samples effectively inhibited cell growth, with cell viability reduced to less than 20% after 2 weeks of experimentation. These findings demonstrate that the sequential chitosan coating method offers superior drug entrapment and prolonged release compared to mixing chitosan once, exhibiting its potential as a sustained drug delivery system for cancer treatment. Full article

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres. Full article

Long-acting injectable (LAI) formulations have revolutionized veterinary pharmaceuticals by improving patient compliance, minimizing dosage frequency, and improving therapeutic efficacy. These formulations utilize advanced drug delivery technologies, including microspheres, liposomes, oil solutions/suspensions, in situ-forming gels, and implants to achieve extended drug release. Biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL) have been approved by the USFDA and are widely employed in the development of various LAIs, offering controlled drug release and minimizing the side effects. Various classes of veterinary medicines, including non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and reproductive hormones, have been successfully formulated as LAIs. Some remarkable LAI products, such as ProHeart^® (moxidectin), Excede^® (ceftiofur), and POSILACTM (recombinant bovine somatotropin), show clinical relevance and commercial success. This review provides comprehensive information on the formulation strategies currently being used and the emerging technologies in LAIs for veterinary purposes. Additionally, challenges in characterization, in vitro testing, in vitro in vivo correlation (IVIVC), and safety concerns regarding biocompatibility are discussed, along with the prospects for next-generation LAIs. Continued advancement in the field of LAI in veterinary medicine is essential for improving animal health. Full article

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article

We propose a pulsed modulated digital holographic microscopy (PM-DHM) technique for the dynamic measurement of flowing microparticles in microfluidic systems. By digitally tuning the pulse width and the repetition rate of a laser source within a single-frame exposure, this method enables the recording of multiple images of flowing microparticles at different time points within a single hologram, allowing the quantification of velocity and acceleration. We demonstrate the feasibility of PM-DHM by measuring the velocity, acceleration, and forces exerted on PMMA microspheres and red blood cells flowing in microfluidic chips. Compared to traditional frame-sampling-based imaging methods, this technique has a much higher time resolution (in a range of microseconds) that is limited only by the pulse duration. This method demonstrates significant potential for high-throughput label-free flow cytometry detection and offers promising applications in drug development and cell analysis. Full article

Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. Ramulus Mori alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. Full article