Polylactic Glycolic Acid Research Articles

A PLGA/Silk Fibroin Nanofibre Membrane Loaded with Natural Flavonoid Compounds Extracted from Green Cocoons for Wound Healing.

The use of biodegradable materials combined with natural metabolites in wound dressings has received much attention. Flavonoids (FLs) from green cocoons, as metabolites, have antibacterial, antioxidant, anti-inflammatory, and other pharmacological effects. In this study, composite membranes of FL-loaded polylactic glycolic acid (PLGA)/silk fibroin (SF) were prepared by an electrospinning method. The prepared membranes, including SF, exhibited a good slow-release effect and cytocompatibility. An in vitro evaluation of the FL-loaded PLGA/SF membranes demonstrated good antioxidant, antibacterial, and anti-inflammatory properties. Animal experiments showed that the wound healing rate of PLGA/SF-2.5FL membranes within 15 days was 97.3%, and that of the control group was 72.5%. The PLGA/SF-2.5FL membranes shortened the inflammatory period of a full-layer wound model and promoted skin regeneration and wound healing by downregulating expression of the pro-inflammatory cytokines IL-1β and TNF-α and promoting expression of the growth factors VEGF, TGF-β, and EGF. In summary, the PLGA/SF-2.5FL composite nanofibre membrane with anti-inflammatory properties is an ideal wound dressing to promote acute wound healing.

Carrier cascade target delivery of 5-aminolevulinic acid nanoplatform to enhance antitumor efficiency of photodynamic therapy against lung cancer

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.

Glial scarring around intra-cortical MEA implants with flexible and free microwires inserted using biodegradable PLGA needles.

Introduction: Many invasive and noninvasive neurotechnologies are being developed to help treat neurological pathologies and disorders. Making a brain implant safe, stable, and efficient in the long run is one of the requirements to conform with neuroethics and overcome limitations for numerous promising neural treatments. A main limitation is low biocompatibility, characterized by the damage implants create in brain tissue and their low adhesion to it. This damage is partly linked to friction over time due to the mechanical mismatch between the soft brain tissue and the more rigid wires. Methods: Here, we performed a short biocompatibility assessment of bio-inspired intra-cortical implants named "Neurosnooper" made of a microelectrode array consisting of a thin, flexible polymer-metal-polymer stack with microwires that mimic axons. Implants were assembled into poly-lactic-glycolic acid (PLGA) biodegradable needles for their intra-cortical implantation. Results and Discussion: The study of glial scars around implants, at 7days and 2months post-implantation, revealed a good adhesion between the brain tissue and implant wires and a low glial scar thickness. The lowest corresponds to electrode wires with a section size of 8μm × 10μm, compared to implants with the 8μm × 50μm electrode wire section size, and a straight shape appears to be better than a zigzag. Therefore, in addition to flexibility, size and shape parameters are important when designing electrode wires for the next generation of clinical intra-cortical implants.

Preparation of salicylic acid nano-protectant with dual synergistic mechanism: High direct fungicidal activity and plant defence toward cotton Verticillium wilt

Nanomaterials exhibit a wide range of potential applications in agricultural field. Here we construct a series of nano-protectants based on one model plant elicitor salicylic acid (SA) and six types of nanomaterials, including mesoporous silica nanosphere (MSN), mesoporous Fe3O4 nanosphere (Fe3O4), carbon quantum dot (CQD), polylactic acid-glycolic acid copolymer (PLGA), star polycation (SPc) and hydrophilic and lipophilic diblock polymer (HLDP), and explore the best nanomaterial for plant disease control. Our results demonstrate that the HLDP-SA nano-protectant displays the best control effects on cotton Verticillium wilt caused by one of the most notorious soil-borne fungi (Verticillium dahliae). The HLDP self-assembles with SA via electrostatic interaction into HLDP-SA nano-protectant, which changes the morphology of SA from needle-like particles to spherical particles. The loading efficiency of HLDP toward SA is calculated to be 49.28%, and the plant uptake of HLDP-loaded SA significantly increases by 3–4 times. HLDP-SA nano-protectant can suppress the spore germination of V991 strain with the spore germination rate of merely 2%, and its colony diameter is significantly decreased by 64.9%. Our transcriptome data demonstrate that the HLDP-SA nano-protectant accelerates the delivery and translocation of exogenous substances into V. dahliae, which exhibits the highest direct fungicidal activity via inhibiting the metabolism and weakening the pathogenicity. Meanwhile, its enhanced plant uptake with better adhesion performance on leaves amplifies the plant defense induced by SA via accelerating the biosynthesis of plant secondary metabolites, such as SA, abscisic acid (ABA) and gossypol. This study provides a powerful nanomaterial with dual synergistic mechanism for designing nano-protectant with high fungicidal activity and amplified plant defense.

A poly (lactic-co-glycolic acid) self-pumping Janus dressing with bidirectional biofluid transport for diabetic wound healing via anti-bacteria and pro-angiogenesis

Diabetic wound healing poses a substantial challenge owing to bacterial infections, insufficient angiogenesis, and excessive exudates. Currently, most of the clinical dressings used for diabetic wounds are still conventional dressings such as gauze. In this study, a three-layer Janus dressing was developed via continuous electrostatic spinning. The top-layer was composed of polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate. The hydrophobic top-layer prevented the adhesion of foreign bacteria. The mid-layer was composed of polyethylene glycol, polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate facilitated exudate absorption and bioactive ion release. The modified sub-layer containing polylactic acid-glycolic acid, hydroxyapatite doped with silver ions and silicate and sodium alginate microspheres enabled both the transport of wound exudate from the wound bed to dressing and the backflow of bioactive silver ions and silicate to the wound bed, thereby reducing infection and stimulating angiogenesis. Through in vivo and in vivo experiments, the Janus dressing showed to have antimicrobial, angiogenic, and exudate-control properties that accelerate healing in diabetic wounds. As a novel dressing, the multifunctional, self-pumping Janus wound dressing with bi-directional biofluidic transport offers a new approach to diabetic wound healing.

A sono-responsive antibacterial nanosystem co-loaded with metformin and bone morphogenetic protein-2 for mitigation of inflammation and bone loss in experimental peri-implantitis

BackgroundDental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.MethodsIn this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.ResultsThe results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-α and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.ConclusionOur observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.

Integration of BMP-2/PLGA microspheres with the 3D printed PLGA/CaSO4 scaffold enhances bone regeneration

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.

Composite Hydrogel Containing Collagen-Modified Polylactic Acid-Hydroxylactic Acid Copolymer Microspheres Loaded with Tetramethylpyrazine Promotes Articular Cartilage Repair.

Articular cartilage defects pose a significant challenge due to the limited self-healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of the polylactic acid-glycolic acid (PLGA) and collagen-surface modified polylactic acid-glycolic acid (CPLGA) microspheres loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. CPLGA microspheres are prepared by Steglich reaction and characterized. They evaluated the effect of TMP-loaded microspheres on HUVECs (Human Umbilical Vein Endothelial Cells) and examined the compatibility of blank microspheres with BMSCs (Bone marrow mesenchymal stromal cells) and their potential to promote cartilage differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen-induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP-loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere-composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation.

Macrophage membrane-coated Eucommia ulmoides polysaccharides-loaded PLGA nanoparticles as an effective antigen-targeted delivery system

Polysaccharides derived from Eucommia ulmoides leaves have immune-regulating, hypoglycemic, anti-tumor, and other beneficial functions. As a drug delivery system, polylactic-glycolic acid copolymer (PLGA) offers advantages like immunogenicity enhancement, improved drug absorption, and increased drug bioavailability. Currently, macrophage membranes are successfully employed in biomimetic nanomaterials to enhance drug utilization and extend drug administration time in the body, exhibiting good immunogenicity and organ targeting. In this study, we developed biomimetic PsEUL PLGA nanoparticles (NPs) coated with macrophage membrane (MM-PPsEUL) and examined their immune activity in vitro and in vivo. In vitro, MM-PPsEUL increased the phagocytic efficiency of macrophages without affecting their activity. In vivo, MM-PPsEUL significantly elevated the immune organ index of mice and upregulated the level of ovalbumin-specific IgG antibodies in serum. Simultaneously, it increased the expressions of cytokines IFN-γ and IL-4, as well as the levels of TLR4, MyD88, TRAF6, and NF-κB p65 proteins in mice spleen. MM-PPsEUL also exhibited a targeting effect on inguinal lymph nodes and slowed down the release rate of antigens, thereby inducing a prolonged immune response. In summary, MM-PPsEUL provides sustained release capabilities and can induce both humoral and cellular immune responses. This makes MM-PPsEUL NPs a promising antigen-targeted delivery system.

Spray Coating of Wood with Nanoparticles from Lignin and Polylactic Glycolic Acid Loaded with Thyme Essential Oils.

Ensuring the longevity of wooden constructions depends heavily on the preservation process. However, several traditional preservation methods involving fossil-based compounds have become outdated because they pose a significant risk to the environment and to human health. Therefore, the use of bio-based and bioactive solutions, such as essential oils, has emerged as a more sustainable alternative in protecting wood from biotic attacks. The entrapment of essential oils in polymeric carrier matrices provides protection against oxidation and subsequent degradation or rapid evaporation, which implies the loss of their biocidal effect. In this work, lignin as well as PLGA nanoparticles containing the essential oils from two different thyme species (Thymus capitatus and T. vulgaris) were applied on beech wood samples using spray coating. The prepared coatings were investigated using FTIR imaging, SEM, as well as LSM analysis. Release experiments were conducted to investigate the release behavior of the essential oils from their respective lignin and PLGA carrier materials. The study found that lignin nanoparticles were more effective at trapping and retaining essential oils than PLGA nanoparticles, despite having larger average particle diameters and a more uneven particle size distribution. An analysis of the lignin coatings showed that they formed a uniform layer that covered most of the surface pores. PLGA nanoparticles formed a film-like layer on the cell walls, and after leaching, larger areas of native wood were evident on the wood samples treated with PLGA NPs compared to the ones coated with lignin NPs. The loading capacity and efficiency varied with the type of essential oil, while the release behaviors were similar between the two essential oil types applied in this study.

Fibroblasts/three-dimensional scaffolds complexes promote wound healing in rats with skin defects

ABSTRACT We aim to construct a three-dimensional nano-skin scaffold material in vitro and study its promoting effect on wound healing in vivo. In this study, hybrid constructs of three-dimensional (3D) scaffolds were successfully fabricated by combination of type I collagen (COL-1) and polylactic-glycolic acid (PLGA). Fibroblasts and human umbilical cord mesenchymal stem cells (hUCMSCs) were used to implanted into 3D scaffolds and constructed into SD skin scaffolds in vitro. Finally, the fibroblasts/scaffolds complexes were inoculated on the surface of rat wound skin to study the promoting effect of the complex on wound healing. In our study, we successfully built a 3D scaffold, which had a certain porosity. Meanwhile, the content of COL-1 in the cell supernatant of fibroblast/scaffold complexes was increased. Furthermore, the expression of F-actin, CD105, integrin β, VEGF, and COL-1 was up-regulated in hUCMSC/scaffold complexes compared with the control group. In vivo, fibroblast/scaffold complexes promoted wound healing in rats. Our data suggested that the collagen Ⅳ and vimentin were elevated and collagen fibers were neatly arranged in the fibroblast/scaffold complex group was significantly higher than that in the scaffold group. Taken together, fibroblast/scaffold complexes were expected to be novel materials for treating skin defects.

Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Polylactic Glycolic Acid-Mediated Delivery of Plectasin Derivative NZ2114 in Staphylococcus epidermidis Biofilms.

Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid-glycolic acid (PLGA)-polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion-solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity against Staphylococcus epidermidis (S. epidermidis) (4-8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population of S. epidermidis G4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused by S. epidermidis.

HepG2 exosomes coated luteolin nanoparticles remodeling hepatic stellate cells and combination with sorafenib for the treatment of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to activated hepatic stellate cells (HSCs). The natural product luteolin is good at alleviating the activation of HSC. However, its clinical application is limited to poor solubility, bioavailability and lacking of HSCs targeting effects. This study aims to construct luteolin-loaded biomimetic nanoparticles based on HepG2 exosomes for targeting HSCs and enhancing the therapeutic effects of sorafenib on HCC.MethodsThe HepG2 exosomes extracted were identified by size distribution, Zeta potential and characteristic proteins. Luteolin-loaded polylactic acid-glycolic acid (PLGA) nanoparticles (Lut-NPs) were prepared and wrapped by HepG2 exosomes to form biomimetic nanoparticles (Exo-Lut-NPs). A HepG2 cell sorafenib-resistant model induced by LX2 cell conditioned medium (CM) was established to evaluate the effects of Exo-Lut-NPs on reversing sorafenib-resistant in vitro. And the combined therapeutic effects of Exo-Lut-NPs with sorafenib were evaluated on a HepG2/LX2 subcutaneous xenograft tumor model in vivo.ResultsThe particle size, drug loading capacity and encapsulation efficiency of Exo-Lut-NPs were 165 ± 10 nm, 2.6 ± 0.2% and 56.9 ± 4.3%, respectively. The in vitro HepG2 sorafenib-resistant model was induced by the CM of LX2 cells, and the results showed that Exo-Lut-NPs partially reversed the sorafenib resistance of HepG2 cells by affecting the CM of LX2 cells. The combined therapy of Exo-Lut-NPs with sorafenib markedly suppressed tumor growth in a HepG2/LX2 subcutaneous xenograft tumor model.ConclusionsThis study suggests that the Exo-Lut-NP is a novel and promising biomimetic delivery system which can combine with sorafenib for HCC therapy.

Polyvinyl alcohol/collagen composite scaffold reinforced with biodegradable polyesters/gelatin nanofibers for adipose tissue engineering

Breast cancer has become the most diagnosed cancer type, endangering the health of women. Patients with breast resection are likely to suffer serious physical and mental trauma. Therefore, breast reconstruction becomes an important means of postoperative patient rehabilitation. Polyvinyl alcohol hydrogel has great potential in adipose tissue engineering for breast reconstruction. However, its application is limited because of the lack of bioactive factors and poor structural stability. In this study, we prepared biodegradable polylactic acid-glycolic acid copolymer/polycaprolactone/gelatin (PPG) nanofibers. We then combined them with polyvinyl alcohol/collagen to create tissue engineering scaffolds to overcome limitations. We found that PPG fibers formed amide bonds with polyvinyl alcohol/collagen scaffolds. After chemical crosslinking, the number of amide bonds increased, leading to a significant improvement in their mechanical properties and thermal stability. The results showed that compared with pure PVA scaffolds, the maximum compressive stress of the scaffold doped with 0.9 g nanofibers increased by 500 %, and the stress loss rate decreased by 40.6 % after 10 cycles of compression. The presence of natural macromolecular gelatin and the changes in the pore structure caused by nanofibers provide cells with richer and more three-dimensional adsorption sites, allowing them to grow in three dimensions on the scaffold. So, the hydrogel scaffold by reinforcing polyvinyl alcohol hydrogel with PPG fibers is a promising breast reconstruction method.

DOX-PLGA Nanoparticles Effectively Suppressed the Expression of Pro-Inflammatory Cytokines TNF-a, IL-6, iNOS, and IL-1β in MCF-7 Breast Cancer Cell Line.

Inflammation contributes to cancer pathobiology through different mechanisms. Higher levels of pro-inflammatory cytokines can lead to hyperinflammation and promote cancer development and metastasis. For cancer treatment, Doxorubicin (DOX) can be encapsulated into the poly-lactic-glycolic acid (PLGA) nanoparticles. This study aimed to investigate the impact of doxorubicin-loaded PLGA nanoparticles (DOX-PLGA NP) on the expression of pro-inflammatory genes TNF-α, IL-6, iNOS, and IL-1β in the MCF-7 cells. The DOX-PLGA NP was prepared by loading doxorubicin into PLGA and characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxic effect of the nanoparticles was determined by the MTT assay, and their impacts on the expression of pro-inflammatory genes were assessed by qRT-PCR. The encapsulation efficiency and loading capacity were 60±1.5 and 1.13±0.21 percent, respectively. The zeta potential and mean DOX-PLGA nanoparticle size were -18±0.550 mV and 172±55.6 nm, respectively. The 50% inhibitory concentration (IC50) of the DOX-PLGA NP on MCF-7 cell viability was 24.55 µg/mL after 72 hours of treatment. The qRT-PCR results revealed that the 20 µg/mL concentration of the DOX-PLGA NP significantly suppressed the expression of the pro-inflammatory genes TNF-α, IL-6, iNOS, and IL-1β compared to DOX alone (20 µg/mL). Additionally, the suppression effect of DOX-PLGA NP on the expression of these pro-inflammatory genes was dose-dependent. These results show that DOX-PLGA NP efficiently suppressed the expression of pro-inflammatory genes. Furthermore, encapsulation of DOX into PLGA nanoparticles significantly improved the effectiveness of DOX in suppressing pro-inflammatory genes in MCF-7 breast cancer cells.

A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble.

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. SPIO/TP53/PLGA NBs with a particle size of approximately 200nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

Screening of Process Parameters for Aspirin Loaded PLGA Microsphere

Background amp Aim Aspirin a non-steroidal anti-inflammatory drug has the potential to stimulate various dental stem cells and promotes regeneration of dental tissues. Polylactic glycolic acid PLGA a biocompatible and biodegradable polymer has the potential to stimulate multiple processes such as proliferation osteogenic differentiation initiation of mechanical support and formation of three-dimensional niches for the growth of new tissue. Hence this study aimed to identify the most effective formulation and process variables for developing aspirin polylactic glycolic acid microspheres using the Placket-Burman method.Method In the screening study Placket-Burman screening was systematically employed to estimate all of the parameter effects and interactions. The microspheres were formulated using the double-emulsion solvent extraction method by varying various variables and performing statistical analysis. Eight independent variables were considered for screening with encapsulation efficiency as the dependent variable. These variables included the volume of the internal phase of primary emulsion solvent system ethyl acetate ethanol homogenization time stirring speed emulsification time flow rate poly vinyl alcohol concentration and PLGA concentration.Results Encapsulation efficiency varied between 50.11 and 88.98. The concentration of PLGA and Poly vinyl alcohol and the volume of the internal phase were found to have a significant influence on encapsulation efficiency in the synthesis of Aspirin PLGA microsphere.Conclusion Among the eight independent variables assessed for screening the concentrations of PLGA and polyvinyl alcohol and the volume of the internal phase were found to significantly impact the encapsulation efficiency in the formulation of aspirin PLGA microspheres.

Regulation of the immune microenvironment by pioglitazone-loaded polylactic glycolic acid nanosphere composite scaffolds to promote vascularization and bone regeneration

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration of blood vessels, and other factors must be considered in bone tissue engineering. To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid–glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid–glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2/Smad/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K/AKT/HIF1-/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres—which contain the drug PIO—are combined with ATP/PVA/GEL scaffolds.

Preliminary Study on Pharmacokinetics and Antitumor Pharmacodynamics of Folic Acid Modified Crebanine Polyethyleneglycol-Polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles.

Liver cancer is associated significantly with morbidity and mortality. The combination of low-intensity ultrasound with nanomedicine delivery systems holds promise as an alternative for the treatment for liver cancer. This study focuses on the utilization of folic acid (FA) modified nanoparticles, which are loaded with fluorescent dye DiR and liquid fluorocarbon (PFP). These nanoparticles have the potential to enhance liver cancer targeting under ultrasound stimulation and future applications in vivo. The pharmacokinetics and tissue distribution of folic acid-modified Crebanine polyethylene glycol-polylactic acid copolymer nanoparticles (FA-Cre@PEG-PLGA NPs) were investigated. The pharmacokinetic parameters, liver targeting, and in vivo distribution were assessed. Additionally, the inhibitory impacts of FA-Cre@PEG-PLGA NPs in combination with ultrasonic irradiation on the proliferation and acute toxicity of H22 cells of mouse hepatoma were investigated in vitro. The tumor targeting and anti-tumor efficacy of FA-Cre@PEG-PLGA NPs were assessed utilizing a small animal in vivo imaging system and an in situ hepatocellular carcinoma transplantation model, respectively. The pharmacokinetic studies and tissue distribution tests demonstrated that FA-Cre@PEG-PLGA NPs conspicuously prolonged the half-life and retention time of the drug in rats, and the liver targeting effect was pronounced. Additionally, the in vivo acute toxicity test indicated that FA-Cre@PEG-PLGA NPs had minimal adverse reactions and could fulfill the aim of attenuating the drug. The outcomes of the animal experiments further substantiated that FA-Cre@PEG-PLGA NPs had a longer retention time at the tumor site, a superior anti-tumor effect, and less damage to liver and kidney tissue. The integration of FA-Cre@PEG-PLGA NPs with ultrasound irradiation demonstrated exceptional safety and potent anti-tumor efficacy in vivo, presenting a promising therapeutic strategy for the treatment of liver cancer through the combination of ultrasound technology with a nanomedicine delivery system.