Search Results (286)

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Poly(lactide-co-glycolide) (PLGA) implants have become a cornerstone in drug delivery and regenerative medicine due to their biocompatibility, tunable degradation, and capacity for sustained, localized therapeutic release. Recent innovations in polymer design, fabrication methods, and functional modifications have expanded their utility across diverse clinical domains, including oncology, neurology, orthopedics, and ophthalmology. This review provides a comprehensive analysis of PLGA implant properties, fabrication strategies, and biomedical applications, while addressing key challenges such as burst release, incomplete drug release, manufacturing complexity, and inflammatory responses. Emerging solutions—such as 3D printing, in situ forming systems, predictive modeling, and patient-specific customization—are improving implant performance and clinical translation. Emphasis is placed on scalable production, long-term biocompatibility, and personalized design to support the next generation of precision therapeutics. Full article

Background/Objectives: A novel 3D-printed, bioresorbable bone graft, made of nanohydroxyapatite (nHAP) covered by poly(lactide-co-glycolide) (PLGA), showed strongly expressed osteoinductive properties in our previous investigations. The current study examines its application in the dual regeneration of bone and cartilage by combining with nHAP gel obtained by nHAP enrichment with hydroxyethyl cellulose, sodium hyaluronate, and chondroitin sulfate. Methods: In the in vitro part of the study, the mitochondrial activity and osteogenic and chondrogenic differentiation of stem cells derived from apical papilla (SCAPs) in the presence of nHAP gel were investigated. For the in vivo part of the study, three rabbits underwent segmental osteotomies of the lateral condyle of the femur, and defects were filled by 3D-printed grafts customized to the defect geometry. Results: In vitro study revealed that nHAP gel displayed significant biocompatibility, substantially increasing mitochondrial activity and facilitating the osteogenic and chondrogenic differentiation of SCAPs. For the in vivo part of the study, after a 12-week healing period, partial resorption of the graft was observed, and lamellar bone tissue with Haversian systems was detected. Histological and stereological evaluations of the implanted grafts indicated successful bone regeneration, marked by the infiltration of new bone and cartilaginous tissue into the graft. The existence of osteocytes and increased vascularization indicated active osteogenesis. The hyaline cartilage near the graft showed numerous new chondrocytes and a significant layer of newly formed cartilage. Conclusions: This study demonstrated that tailored 3D-printed bone grafts could efficiently promote the healing of substantial bone defects and the formation of new cartilage without requiring supplementary biological factors, offering a feasible alternative for clinical bone repair applications. Full article

There is currently a demand for anti-adhesive materials that are capable of preventing the formation of intra-abdominal adhesions. In this study, electrospun poly(lactide-co-glycolide) scaffolds were dip-coated in aqueous solutions of polyvinyl alcohol with concentrations of 3 wt.%, 6 wt.% and 9 wt.% to obtain a nontoxic and anti-adhesive biomedical material. The viscosities of the applied 3 wt.%, 6 wt.% and 9 wt.% polyvinyl alcohol solutions were 7.7 mPa∙s, 38.2 mPa∙s and 180.8 mPa∙s, respectively, and increased exponentially. It is shown that increasing the viscosity of the polyvinyl alcohol solution from 6 wt.% to 9 wt.% increases the thickness of the polyvinyl alcohol layer from (3.32 ± 0.97) µm to (8.09 ± 1.43) µm. No pronounced polyvinyl alcohol layer can be observed on samples dip-coated in 3 wt.% PVA solution. Increasing the viscosity of the polyvinyl alcohol solution from 3 wt.% to 9 wt.% increases the mechanical properties of the poly(lactide-co-glycolide) samples by a factor of 1.16–1.45. Cytotoxicity analysis of all samples reveals that none is toxic to 3T3-L1 fibroblast cells. A cell adhesion assay indicates that the anti-adhesion properties increase with increasing viscosity of the polyvinyl alcohol solution and the thickness of the polyvinyl alcohol layer on the poly(lactide-co-glycolide) scaffolds. Fluorescence images of the cells show that as the thickness of the polyvinyl alcohol coating increases, the number of cells decreases, and they do not cover the surface of the samples and form spherical three-dimensional agglomerates. The highest mechanical and anti-adhesion properties are obtained with the poly(lactide-co-glycolide) scaffold sample dip-coated in the 9 wt.% polyvinyl alcohol solution. This is because this sample has the thickest polyvinyl alcohol coating. Full article

Poly(D,L-lactide-co-glycolide) (PLGA) has emerged as a cornerstone in the development of advanced drug delivery systems, particularly for intranasal and pulmonary routes. Its biodegradability, biocompatibility, and adaptability make it an ideal platform for addressing challenges associated with conventional therapies. By enabling sustained and controlled drug release, PLGA formulations reduce dosing frequency, improve patient compliance, and enhance therapeutic efficacy. These systems demonstrate versatility, accommodating hydrophilic and hydrophobic drugs, biological molecules, and co-delivery of synergistic agents. Moreover, surface modifications and advanced preparation techniques enhance targeting, bioavailability, and stability, expanding PLGA’s applications to treat complex diseases such as tuberculosis, cancer, pulmonary fibrosis, and CNS disorders. This manuscript provides an in-depth review of PLGA’s materials, properties, preparation methods, and therapeutic applications, alongside a critical evaluation of challenges and future opportunities in this field. Full article

Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine. Innovations in polymer chemistry, surface functionalization, and advanced manufacturing techniques, such as microfluidics and electrospraying, have further enhanced the efficacy and scalability of these systems. This review highlights the key physicochemical properties, preparation strategies, and proven benefits of peptide-loaded PLGA systems, emphasizing their role in sustained drug release, immune activation, and tissue regeneration. Despite remarkable progress, challenges such as production scalability, cost, and regulatory hurdles remain. Full article

Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. Methods: Poly(lactide-co-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. Results: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. Conclusions: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels. Full article

Background/Objectives: Camptothecin (CPT) is a well-known chemical compound recognized for its significant anticancer properties. However, its clinical application remains limited due to challenges related to CPT’s high hydrophobicity and the instability of its active form. To address these difficulties, our research focused on the development of four novel nanoparticulate systems intended for either oral or intravenous administration. Methods: These nanosystems were based on a poly(amidoamine) (PAMAM) dendrimer/CPT complex, which had been coated with biodegradable homo- and copolymers, designed with appropriate physicochemical properties and chain microstructures. Results: The resulting nanomaterials, with diameters ranging from 110 to 406 nm and dispersity values between 0.10 and 0.67, exhibited a positive surface charge and were synthesized using biodegradable poly(L-lactide) (PLLA), poly(L-lactide-co-ε-caprolactone) (PLACL), and poly(glycolide-co-ε-caprolactone) (PGACL). Biological assessments, including cell viability and hemolysis tests, indicated that all polymers demonstrated less than 5% hemolysis, confirming their hemocompatibility for potential intravenous use. Furthermore, fibroblasts exposed to these matrices showed concentration-dependent viability. The entrapment efficiency (EE) of CPT reached up to 27%, with drug loading (DL) values as high as 17%. The in vitro drug release studies lasted over 400 h with the use of phosphate buffer solutions at two different pH levels, demonstrating that time-dependent processes allowed for a gradual and controlled release of CPT from the developed nanosystems. The release kinetics of the active compound at pH 7.4 ± 0.05 and 6.5 ± 0.05 followed near-first-order or first-order models, with diffusion and Fickian/non-Fickian transport mechanisms. Importantly, the nanoparticulate systems enabled the stabilization of the pharmacologically active form of CPT, while providing protection against hydrolysis, even in physiological environments. Conclusions: In our opinion, these results underscore the promising future of biodegradable nanosystems as effective drug delivery systems (DDSs) for targeted cancer treatment, offering stability and efficacy over short, medium, and long-term applications. Full article

Background/Objectives: Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, isolated from the roots of Euclea natalensis A. DC. Methods: 7-MJ as well as its respective PLGA nanoparticles were tested for their antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) (H37Rv), and multi-drug-resistant M. tuberculosis (MDR11). The cytotoxicity of 7-MJ as well as its respective PLGA nanoparticles were tested for their cytotoxic effect against differentiated human histiocytic lymphoma (U937) cells. Engulfment studies were also conducted to determine whether the PLGA nanoparticles are taken up by differentiated U937 cells. Results: 7-MJ has been shown to have a minimum inhibitory concentration (MIC) value of 1.6 µg/mL against M. smegmatis and multi-drug-resistant M. tuberculosis and 0.4 µg/mL against drug-susceptible M. tuberculosis. Whilst promising, 7-MJ was associated with cytotoxicity, with a fifty percent inhibition concentration (IC₅₀) of 3.25 µg/mL on differentiated U937 cells. In order to lower the cytotoxic potential, 7-MJ was loaded into PLGA nanoparticles. The 7-MJ PLGA nanoparticles showed an 80-fold decrease in cytotoxic activity compared to free 7-MJ, and the loaded nanoparticles were successfully taken up by differentiated macrophage-like U937 cells. Conclusions: The results of this study suggested the possibility of improved delivery during TB therapy via the use of PLGA nanoparticles. Full article

Background/Objectives: The escalating challenge of antimicrobial resistance (AMR) necessitates the development of targeted antibiotic delivery platforms, minimising systemic administration. Polymer-based drug delivery emerges as a promising solution, ensuring sustained release and prolonged efficacy of bioactive compounds, ensuring long-term efficacy. Methods: This study focuses on encapsulating rifampicin (RIF), a key antibiotic for orthopaedic and wound-related infections, within Poly(d,l-lactide-co-glycolide) (PLGA), a biodegradable polymer, through solvent casting, to formulate a PLGA-RIF composite membrane. Comprehensive characterisation, employing Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermal analysis and X-ray Diffraction (XRD), confirmed the integrity of both the starting and produced materials. UV-Vis spectroscopy revealed a controlled drug release profile over 21 days in various media, with the chosen media influencing the drug release, notably the tryptic soya broth (TSB) caused the highest release. The quantitative assessment of the antimicrobial efficacy of the developed PLGA-RIF composite was conducted by measuring the size of the inhibition zones against both Gram-negative and Gram-positive bacteria. Results: The results confirmed the composite’s potential as a robust antibacterial biomaterial, demonstrating a rapid and effective antibacterial response. Cytocompatibility tests incorporated human fibroblast and osteoblast-like cell lines and demonstrated that the RIF:PLGA (1:8) formulation maintained eukaryotic cell viability, indicating the composite’s potential for targeted medical applications in combating bacterial infections with minimal systemic impact. Conclusions: This study presents the significance of investigating drug release within appropriate and relevant physiological media. A key novelty of this work therefore lies in the exploration of drug release dynamics across different media, allowing for a comprehensive understanding of how varying physiological conditions may influence drug release and its effect on biological responses. Full article

Background/Objectives: An inhibitor of small Rho GTPase Cdc42, CASIN, has been shown to reduce cancer cell proliferation, migration, and invasion, yet it has several limitations, including rapid drug elimination and low bioavailability, which prevents its systemic administration. In this study, we designed and characterized a nanoparticle-based delivery system for CASIN encapsulated within poly(lactide-co-glycolide)-block-poly(ethylene glycol)-carboxylic acid endcap nanoparticles (PLGA-PEG-COOH NPs) for targeted inhibition of Cdc42 activity in colon cancer. Methods: We applied DLS, TEM, and UV–vis spectroscopy methods to characterize the size, polydispersity index, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release of the synthesized nanoparticles. The CCK-8 cell viability test was used to study colorectal cancer cell growth in vitro. Results: We showed that CASIN-PLGA-PEG-COOH NPs were smooth, spherical, and had a particle size of 86 ± 1 nm, with an encapsulation efficiency of 66 ± 5% and a drug-loading capacity of 5 ± 1%. CASIN was gradually released from NPs, reaching its peak after 24 h, and could effectively inhibit the proliferation of HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM) cells in concentrations ranging between 0.025–0.375 mg/mL. CASIN-PLGA-PEG-COOH NPs demonstrated low hemolytic activity with a hemolytic ratio of less than 1% for all tested concentrations. Conclusion: CASIN-PLGA-PEG-COOH NPs have high encapsulation efficiency, sustained drug release, good hemocompatibility, and antitumor activity in vitro. Our results suggest that PLGA-PEG-COOH nanoparticles loaded with CASIN show potential as a targeted treatment for colorectal cancer and could be recommended for further in vivo evaluation. Full article

In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL–PEG–PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels’ mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA–PEG–PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG–polyester nanoparticles loaded with IgG in a PLGA–PEG–PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (T_GEL) value and increased the storage modulus of the gels, as compared with gels without IgG. The prepared gel materials were able to release the IgG from 8 up to 80 days, depending on the gel formulation and on the amount of loaded IgG. The results revealed that additional, chemical crosslinking of the thermogels and also suspension of particles in the polymer matrix substantially extended the duration of IgG release. With proper matching of the gel composition, environmental conditions, and the type and amount of active substances, antibody-containing thermogels can serve as effective IgG delivery materials. Full article

Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of −1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p = 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p = 0.166; average supination: 83.5° vs. 85.7°, p = 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p = 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusions: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries. Full article

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R² = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R² ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products. Full article

Allergic contact dermatitis (ACD) can easily develop once sensitization is established by exposure to small amounts of antigen, and steroids are used for treatment. In this study, we evaluated the therapeutic efficacy of prednisolone (PSL)-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) on a mouse model of contact dermatitis (CHS). Nanoparticles were prepared using a poor solvent diffusion method, and particle size distribution and mean particle size were measured using dynamic light scattering. Treatment experiments with PSL-loaded PLGA NPs were performed before and after sensitization with 1-fluoro-2,4-dinitrobenzene (DNFB), and evaluation was performed by quantifying intracutaneous IL-4 and TNF-α levels in a mouse model of CHS using ELISA. When PSL-loaded PLGA NPs were administered before sensitization, IL-4 expression was significantly decreased, and TNF-α tended to decrease in the group treated with PSL-loaded PLGA NPs compared to the non-treated group. When PSL-loaded PLGA NPs were administered after sensitization, IL-4 expression was significantly decreased in the group treated with PSL-loaded PLGA NPs compared to the non-treated group. In both cases, there were no significant differences between the PSL-loaded PLGA NP treatment group and the PSL-containing ointment group. These results suggest that, in the treatment of CHS, PSL-loaded PLGA NPs show a certain therapeutic effect when preadministration. Full article