Search Results (701)

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 $\mathsf{\mu }$m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

Background/Objectives: Personalized 3D-printed (3DP) metallic implants delivery systems are being explored to repair bone fractures, allowing the customization of medical implants that respond to individual patient needs, making it potentially more effective and of greater quality than mass-produced devices. However, challenges associated with postsurgical infections caused by bacterial adhesion remain a clinical issue. To address this, local antibiotic therapies are receiving extensive attention to minimize the risk of implant-related infections. This study investigated the use of amikacin (AMK), a broad-spectrum aminoglycoside antibiotic, incorporated onto 3D-printed 316L stainless steel implants using biodegradable polymer coatings of chitosan and poly lactic-co-glycolic acid (PLGA). Methods: This research examined different approaches to coat 3DP implants with amikacin. Various polymer-based coatings were studied to determine the optimal formulation based on the characteristics and release profile. The optimal formulation was performed on the antibacterial activity studies. Results: AMK-chitosan with PLGA coating implants controlled the rate of drug release for up to one month. The 3DP drug-loaded substrates demonstrated effective, concentration-dependent antibacterial activity against common infective pathogens. AMK-loaded substrates showed antimicrobial effectiveness for one week and inhibited bacteria significantly compared to the uncoated controls. Conclusions: This study demonstrated that 3DP metal surfaces coated with amikacin can provide customizable drug release profiles while effectively inhibiting bacterial growth. These findings highlight the potential of combining 3D printing with localized delivery strategies to prevent implant-associated infections and advance the development of personalized therapies. Full article

A transdermal drug delivery system based on hydrogel patches was explored, leveraging their sustained release properties and biocompatibility. Despite these advantages, conventional hydrogels often lack proper adhesion to the skin, limiting their practical application. To address this issue, we designed a skin-adhesive hydrogel using a polyacrylamide (PAM)/polydopamine (PDA) dual-network structure. The matrix combines the mechanical toughness of PAM with the strong adhesive properties of PDA, derived from mussel foot proteins, enabling firm tissue attachment and robust performance under physiological conditions. To demonstrate its applicability, the hydrogel was integrated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the hydrophobic antioxidant vitamin E as a model compound. The resulting PAM/PDA@VitE hydrogel system exhibited improved swelling behavior, high water retention, and prolonged release of α-tocopherol. These results suggest that the PAM/PDA hydrogel platform is a versatile vehicle not only for vitamin E, but also for the transdermal delivery of various cosmetic and therapeutic agents. 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

Postoperative adhesions (POAs) are a common and often serious complication following abdominal and gynecologic surgeries, leading to infertility, chronic pain, and bowel obstruction. To address these outcomes, the development of anti-adhesion barriers using biocompatible materials has emerged as a key area of biomedical research. This article presents a comprehensive overview of clinically relevant natural and synthetic biomaterials explored for POA prevention, emphasizing their degradation behavior, barrier integrity, and translational progress. Natural biopolymers—such as collagen, gelatin, fibrin, silk fibroin, and decellularized extracellular matrices—are discussed alongside polysaccharides, including alginate, chitosan, and carboxymethyl cellulose, focusing on their structural features and biological functionality. Synthetic polymers, including polycaprolactone (PCL), polyethylene glycol (PEG), and poly(lactic-co-glycolic acid) (PLGA), are also examined for their tunable degradation profiles (spanning days to months), mechanical robustness, and capacity for drug incorporation. Recent innovations, such as bioprinted and electrospun dual-layer membranes, are highlighted for their enhanced anti-fibrotic performance in preclinical studies. By consolidating current material strategies and fabrication techniques, this work aims to support informed material selection while also identifying key knowledge gaps—particularly the limited comparative data on degradation kinetics, inconsistent definitions of ideal mechanical properties, and the need for more research into cell-responsive barrier systems. Full article

The present study compared the free and encapsulated photosensitizer hypocrellin B (HB) in terms of photophysical-chemical properties, cellular uptake, subcellular distribution, and phototoxicity. The hydrophobic HB was encapsulated into liposomes (HB@Lipo) or poly (lactic-co-glycolic acid) nanoparticles (HB@PLGA). Encapsulation into nanocarriers exerted no obvious influence on the photophysical-chemical properties of HB, including UV-visible absorbance, fluorescence spectra, singlet oxygen (¹O₂) production capacity, and photostability. Free and encapsulated HB revealed some disparities in cellular uptake and subcellular localization patterns. In 2D-cultured B16 cells and tumor spheroids, free HB exhibited the fastest cellular uptake, while HB@PLGA had the lowest, as evidenced. Subcellular localization analysis first revealed a significant colocalization of free HB, HB@Lipo, and HB@PLGA within lipid droplets, with minimal colocalization in mitochondria and the endoplasmic reticulum. Unlike free HB and HB@Lipo, HB@PLGA exhibited strong lysosomal colocalization, indicating a unique intracellular trafficking pathway for PLGA-encapsulated HB. Upon laser irradiation, both free and encapsulated HB induced pronounced phototoxicity with substantial ROS production, confirming the robust PDT effect of HB. The photodynamic killing effect correlated with the intracellular HB content. These findings highlighted the impact of nanoformulation on HB’s cellular behavior and therapeutic performance. Full article

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defect was created, and the following treatments were randomly allocated: sham surgery, deproteinized bovine bone mineral (DBBM) + collagen membrane (CM), poly-(lactic-co-glycolic-acid) (PLGA)-coated pure phase β-tricalcium phosphate (β-TCP), or PLGA-coated 60% hydroxyapatite (HA):40%β-TCP. Animals were allowed to heal for 2 and 6 weeks. Microcomputed tomography (μCT) was used to evaluate mineralized tissue and biomaterial displacement. Histological samples were used to evaluate new bone formation. Results: μCT analysis showed no significant differences among groups for total volume of mineralized tissue or residual biomaterials. DBBM + CM showed significantly increased horizontal biomaterial displacement at 2 weeks but not at 6 weeks. Histological analysis showed that sham surgery had a significantly higher percentage of bone area fraction than the DBBM + CM and PLGA + β-TCP at 2 weeks, but not at 6 weeks. Residual biomaterial area fraction showed no significant differences among experimental groups at any healing time. Conclusions: The alloplastic biomaterials showed suitable construct integrity and retention in the defect. All biomaterials were associated with limited new bone formation comparable to the sham surgery control. Full article

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

This study developed electrosprayed deferoxamine (DFO)-loaded poly(lactic-co-glycolic acid) microspheres (DFO-MS) combined with a sucrose acetate isobutyrate (SAIB) depot (DFO-MS@SAIB) for bone-defect repair, targeting the coordinated regulation of angiogenesis and osteogenesis in vascularized bone regeneration—where new blood vessels support functional bone integration. In vitro/in vivo evaluations confirmed its dual pro-angiogenic and pro-osteogenic effects via HIF-1α pathway activation. Background/Objectives: Emerging evidence underscores the indispensability of vascularization in bone-defect repair, a clinical challenge exacerbated by limited intrinsic healing capacity. While autologous grafts and growth-factor-based strategies remain mainstream, their utility is constrained by donor-site morbidity, transient bioactivity, and poor spatiotemporal control over angiogenic–osteogenic coupling. Here, we leveraged DFO, a hypoxia-mimetic HIF-1α stabilizer with angiogenic potential, to engineer an injectable DFO-MS@SAIB depot. This system was designed to achieve sustained DFO release, thereby synchronizing vascular network formation with mineralized tissue regeneration in critical-sized defects. Methods: DFO-MS were fabricated via electrospraying and combined with SAIB (DFO-MS@S) to form an injectable sustained-release depot. Their physicochemical properties, including morphology, encapsulation efficiency, degradation, release kinetics, and rheology, were systematically characterized. In vitro, the angiogenic capacity of HUVECs co-cultured with DFO-MS was evaluated; conditioned HUVECs were then co-cultured with BMSCs to assess the BMSCs’ cytocompatibility and osteogenic differentiation. In vivo bone regeneration in a rat calvarial defect model was evaluated using micro-CT, histology, and immunohistochemistry. Results: The DFO-MS@SAIB system achieved sustained DFO release, stimulating HUVEC proliferation, migration, and tubulogenesis. In a Transwell co-culture model, pretreated HUVECs promoted BMSC migration and osteogenic differentiation via paracrine signaling involving endothelial-secreted factors (e.g., VEGF). HIF-1α pathway activation upregulated osteogenic markers (ALP, Col1a1, OCN), while in vivo experiments demonstrated enhanced vascularized bone regeneration, with significantly increased bone volume/total volume (BV/TV) and new bone area compared with controls. Conclusion: The DFO-MS@SAIB system promotes bone regeneration via sustained deferoxamine release and HIF-1α-mediated signaling. Its angiogenesis–osteogenesis coupling effect facilitates vascularized bone regeneration, thereby offering a translatable strategy for critical-sized bone-defect repair. Full article

Vegetal sources are a continuous research field and different types of extracts have been obtained over time. The most challenging part is compounding them in a pharmaceutical product. This study aimed to integrate a mixture (EX) of four extracts (SE-Sophorae flos, GE-Ginkgo bilobae folium, ME-Meliloti herba, CE-Calendulae flos) in formulations with polymers (polyhydroxybutyrate, polylactic-co-glycolic acid) and their physicochemical profiling. The resulting samples consist of particle suspensions, which were subjected to Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy analysis. When compared to single-extract formulations spectra, they revealed band changes, depending on the complex interactions. Using X-ray Diffractometry, the partially crystalline phase was highlighted for EX-PLGA, while the others were amorphous. Moreover, Atomic Force Microscopy pointed out the nanoscale particles and the topography of the samples, and the outstanding roughness belonging to EX-PHB-PLGA. A 30 min period of immersion was enough for the formulations to spread on the surface of the compression stockings material (CS) and after drying, it became a polymeric film. TGA analysis was performed, which evaluated the impregnated content: 5.9% CS-EX-PHB, 6.4% CS-EX-PLGA, and 7.5% CS-EX-PHB-PLGA. In conclusion, the extract’s phytochemicals and the interactions established with the polymers or with the other extracts from the mixture have a significant impact on the physicochemical properties of the obtained formulations, which are particularly important in pharmaceutical product development. Full article

We developed a novel biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer chemically modified with paclitaxel (PTX) to form a PLGA-PTX hybrid. Pre-modification of PTX enhanced its loading in PLGA-PTX nanoparticles (NPs). Background/Objectives: PTX is one of the most effective chemotherapy agents used in cancer therapy. The primary mode of PTX’s action is the hyperstabilization of microtubules leading to cell growth arrest. Although highly potent, the drug is water insoluble and requires the Cremophor EL excipient. The toxic effects of the free drug (e.g., neurotoxicity) as well as its solubilizing agent are well established. Thus, there is strong clinical rationale and need for exploring alternative PTX delivery approaches, retaining biological activity and minimizing systemic effects. Methods: The PTX modification method features reacting the C-2′ and C-7 residues with a linker (succinic anhydride) to produce easily accessible carboxyl groups on the PTX for enhanced coupling to the hydroxyl group of PLGA. The PLGA-PTX hybrid, formed via esterification reaction, was used to formulate lipid-coated PLGA-PTX NPs. As proof of concept, the PLGA-PTX NPs were tested in ovarian cancer (OvCA) models, including several patient-derived cell lines (PDCLs), one of which was generated from a platinum-resistant patient. Results: The PLGA-PTX NPs critically remained stable in water and serum while enabling slow drug release. Importantly, PLGA-PTX NPs demonstrated biological activity. Conclusions: We suggest that this approach offers both a new and effective PTX formulation and a possible path towards the development of a new generation of OvCA treatment. 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