Co-glycolic Acid Research Articles

Synthesis of Microwave Functionalized, Nanostructured Polylactic Co-Glycolic Acid (nfPLGA) for Incorporation into Hydrophobic Dexamethasone to Enhance Dissolution.

The low solubility and slow dissolution of hydrophobic drugs is a major challenge for the pharmaceutical industry. In this paper, we present the synthesis of surface-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles for incorporation into corticosteroid dexamethasone to improve its in vitro dissolution profile. The PLGA crystals were mixed with a strong acid mixture, and their microwave-assisted reaction led to a high degree of oxidation. The resulting nanostructured, functionalized PLGA (nfPLGA), was quite water-dispersible compared to the original PLGA, which was non-dispersible. SEM-EDS analysis showed 53% surface oxygen concentration in the nfPLGA compared to the original PLGA, which had only 25%. The nfPLGA was incorporated into dexamethasone (DXM) crystals via antisolvent precipitation. Based on SEM, RAMAN, XRD, TGA and DSC measurements, the nfPLGA-incorporated composites retained their original crystal structures and polymorphs. The solubility of DXM after nfPLGA incorporation (DXM-nfPLGA) increased from 6.21 mg/L to as high as 87.1 mg/L and formed a relatively stable suspension with a zeta potential of -44.3 mV. Octanol-water partitioning also showed a similar trend as the logP reduced from 1.96 for pure DXM to 0.24 for DXM-nfPLGA. In vitro dissolution testing showed 14.0 times higher aqueous dissolution of DXM-nfPLGA compared to pure DXM. The time for 50% (T50) and 80% (T80) of gastro medium dissolution decreased significantly for the nfPLGA composites; T50 reduced from 57.0 to 18.0 min and T80 reduced from unachievable to 35.0 min. Overall, the PLGA, which is an FDA-approved, bioabsorbable polymer, can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower required dosage.

Reactive oxygen species responsive magnetic polylactic co-glycolic acid microspheres: In vitro drug release studies

Reactive oxygen species responsive magnetic polylactic co-glycolic acid microspheres: In vitro drug release studies

Latest research about active pharmaceutical ingredient loaded Poly Lactic Acid-co-Glycolic Acid (PLGA) based drug delivery system in Türkiye

Some of the most well-engineered and produced biomaterials are polyesters based on polyglycolic acid (PGA), polylactic acid (PLA), and their copolymers, polylactic acid co-glycolic acid (PLGA). In controlled release systems, PLGA is the most extensively used and popular polymer. Because of its biodegradability, biocompatibility, and favorable release kinetics, but also because of the reliability of protein delivery issues, this synthetic polymer has been found to be very successful. PLGA is approved in various human drug delivery systems by EMA and FDA. In this review, first, PLGA and historical development, usage, physico-chemical structure, drug release properties, degredation specifications, solubility, crystallinity, thermal stability, release properties, types of PLGA will be mentioned. In the last stage of the review, studies conducted in Türkiye are included. In conclusion, we believe that this review is a resource for researchers doing research with PLGA.

3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria.

Implant-associated infections are not easy to diagnose and very difficult to treat, due to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms and escape the immune response and antibiotic treatment. We, therefore, aimed to develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylactic- co-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured from different PLGA molecular weights was studied in phosphate-buffered saline for 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first 7 days and were selected for antimicrobial evaluation. Four different GelMA-based 3D-printed samples were successfully produced, carrying non-loaded NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S. aureus against increased concentrations of Rif or Van produced new resistant strains to Rif (RifR) or Van (VanR). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 RifR and RN4220 VanR strains. S. aureus RN4220 and S. aureus AMC 201 colonies developed resistance to Rif after contact with the GelMA hydrogel containing only Rif-NPs which appeared to be due to known mutations in the rpoB gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs drug delivery system show promising in vitro results to prevent implant-associated infections caused by antimicrobial-resistant bacteria.

Pharmacokinetic Profiling of Prepared Artemisinin-Loaded Poly(lactic co-glycolic acid) Nanoparticles in Mice Infected with Artemisinin-Sensitive and-Resistant Plasmodium berghei K173 Using by HPLC-MS/MS Assay

Low solubility and bio-availability of artmisinin (ART) limit the clinical efficacy and unfortunately, the resistance of Plasmodium to ART has been gradually reported in recent years. In order to improve its dissolvebility, we therefore prepared ART-loaded poly(lactic co-glycolic acid) (PLGA) nanoparticles and characterized them. Later, the pharmacokinetic differences between ART original materials and artemisinin-loaded nanoparticles in mice infected with ART-sensitive and-resistant Plasmodium berghei K173 were investigated by orally administrated (40 mg/kg) by using a successfully developed and validated LC-MS/MS detection method. ART-loaded nanoparticles exhibited a smooth and spherical shape with average diameters of 193.80±7.65 nm. In vitro release results showed that ART-loaded nanoparticles displayed a stable sustained release effect. Meanwhile, the pharmacokinetic properties of ART-loaded nanoparticles were significantly improved when compared with the crude materials both in two groups. The AUC(0−t) significantly increased 2.91 and 2.85 folds as well as 4.03, 3.61 folds higher half-life period (t1/2) and 2.76, 3.27 folds higher maximum retention time (MRT), respectively. CL, meanwhile, declined 3.33 and 3.33 folds. These results suggested that ART-loaded nanoparticles enhanced the retention of ART in vivo and contributed to its long-lasting antimalarial effect.

Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

The non-canonical inflammasome sensor caspase-11 and gasdermin D (GSDMD) drive inflammation and pyroptosis, a type of immunogenic cell death that favors cell-mediated immunity (CMI) in cancer, infection, and autoimmunity. Here we show that caspase-11 and GSDMD are required for CD8+ and Th1 responses induced by nanoparticulate vaccine adjuvants. We demonstrate that nanoparticle-induced reactive oxygen species (ROS) are size dependent and essential for CMI, and we identify 50- to 60-nm nanoparticles as optimal inducers of ROS, GSDMD activation, and Th1 and CD8+ responses. We reveal a division of labor for IL-1 and IL-18, where IL-1 supports Th1 and IL-18 promotes CD8+ responses. Exploiting size as a key attribute, we demonstrate that biodegradable poly-lactic co-glycolic acid nanoparticles are potent CMI-inducing adjuvants. Our work implicates ROS and the non-canonical inflammasome in the mode of action of polymeric nanoparticulate adjuvants and establishes adjuvant size as a key design principle for vaccines against cancer and intracellular pathogens.

A Review on the Application of Poly Lactic Co-Glycolic Acid in Bone Grafts

The current scenario of dentistry focuses on regeneration for bony defects and associated disorders. For this a thorough understanding of biological and molecular sciences is required. Bone substitutes natural or synthetic act as fillers and scaffolds to regenerate bone and stimulate wound healing. A variety of bone grafts are used in dental practice the most common being alloplasts synthetic bone grafts. Globally 2.2 million bone grafts are placed every year. However there are several challenges yet to overcome. Modifications of existing bone grafts continues to be an expanding subject of interest. Poly DL-lactic co-glycolic acid PLGA - a copolymer of lactic acid and glycolic acid is the rising star in regenerative science which is a complex field. This composite biomaterial retains the properties of both the monomers and can be modified and manipulated into desired forms. Initially PLGA was a desirable candidate for carrier of drug peptides and proteins delivery. Owing to the versatile properties of PLGA it has currently encroached various pharmaceutics medical and dental arenas. This material has been approved by US FDA Food and drug administration as a bone graft substitute. It is believed that PLGA scaffolds can generate osteoconductive and osteoinductive gradient useful for bone formation. This polymer offers the advantages of controlled degradation biocompatibility tunable physiochemical properties and ability to regenerate bone tissues. Also it demonstrates low toxicity in biological tissues. More recently it has revealed its potential as scaffolds 3D printed platforms hydrogels fibers microspheres and nanoparticles. This literature review elaborates the implications of PLGA in regeneration therapy.

Effective breast cancer therapy based on palmitic acid-loaded PLGA nanoparticles

Although new strategies for breast cancer treatment have yielded promising results, most drugs can lead to serious side effects when applied systemically. Doxorubicin (DOX), currently the most effective chemotherapeutic drug to treat breast cancer, is poorly selective towards tumor cells and treatment often leads to the development of drug resistance. Recent studies have indicated that several fatty acids (FAs) have beneficial effects on inhibiting tumorigenesis. The saturated FA palmitic acid (PA) showed anti-tumor activities in several types of cancer, as well as effective repolarization of M2 macrophages towards the anti-tumorigenic M1 phenotype. However, water insolubility and cellular impermeability limit the use of PA in vivo. To overcome these limitations, here, we encapsulated PA into a poly(d,l-lactic co-glycolic acid) (PLGA) nanoparticle (NP) platform, alone and in combination with DOX, to explore PA's potential as mono or combinational breast cancer therapy. Our results showed that PLGA-PA-DOX NPs and PLGA-PA NPs significantly reduced the viability and migratory capacity of breast cancer cells in vitro. In vivo studies in mice bearing mammary tumors demonstrated that PLGA-PA-NPs were as effective in reducing primary tumor growth and metastasis as NPs loaded with DOX, PA and DOX, or free DOX. At the molecular level, PLGA-PA NPs reduced the expression of genes associated with multi-drug resistance and inhibition of apoptosis, and induced apoptosis via a caspase-3-independent pathway in breast cancer cells. In addition, immunohistochemical analysis of residual tumors showed a reduction in M2 macrophage content and infiltration of leukocytes after treatment of PLGA-PA NPs and PLGA-PA-DOX NPs, suggesting immunomodulatory properties of PA in the tumor microenvironment. In conclusion, the use of PA alone or in combination with DOX may represent a promising novel strategy for the treatment of breast cancer.

Topographical and Ultrastructural Evaluation of Titanium Plates Coated with PLGA, Chitosan, and/or Meropenem: An In Vitro Study.

The present investigation was undertaken to evaluate the topographical and ultrastructural architecture of titanium plates coated with polylactic co-glycolic acid (PLGA), chitosan (CH), and/or meropenem (MEM) with or without Staphylococcus aureus (SA) or Pseudomonas aeruginosa (PA) bacteria. Single-hole segments of 0.4 mm thick, low-profile titanium plates were spray coated using an airbrush with polymeric carriers (PLGA or CH) loaded with MEM, in addition to the negative control group (uncoated titanium plates). The coated plates and the negative control group were subjected to bacterial biofilms through a cultivation process while being slowly stirred at 20 rpm for 24 h. The samples were fixed and processed for scanning electron microscopic study at 5, 10, and 20 k magnification. The data were statistically analyzed to compare within and between the different materials. Coating titanium plates with PLGA or CH with MEM appeared to enhance bacterial inhibition over uncoated plates, hindering biofilm formation and preventing bacterial proliferation. In the staphylococcus aureus group, the highest bacterial count was observed in the uncoated plates, whereas the lowest count was detected in meropenem-PLGA, followed by PLGA, chitosan, meropenem, and meropenem-chitosan, respectively. On the other hand, the Pseudomonas aeruginosa group with the uncoated plates had the highest bacterial count, whereas the lowest bacterial count was found related to CH, followed by PLGA, MP, MC, and MEM, respectively.

Immune Modifying Effect of Drug Free Biodegradable Nanoparticles on Disease Course of Experimental Autoimmune Neuritis.

Guillain-Barre syndrome (GBS) is an autoimmune disease of demyelination and inflammation of peripheral nerves. Current treatments are limited to plasma exchange and intravenous immunoglobulins. Cargo-free nanoparticles (NPs) have been evaluated here for their therapeutic benefit on the disease course of experimental autoimmune neuritis (EAN), mimicking the human GBS. NPs prepared from poly-lactic co-glycolic acid (PLGA) with variable size and surface charge (i.e., 500 nm vs. 130 nm, polyvinyl alcohol (PVA) vs. sodium cholate), were intravenously administered in before- or early-onset treatment schedules in a rat EAN model. NP treatment mitigated distinctly the clinical severity of EAN as compared to the P2-peptide control group (P2) in all treatments and reduced the trafficking of inflammatory monocytes at inflammatory loci and diverted them towards the spleen. Therapeutic treatment with NPs reduced the expression of proinflammatory markers (CD68 (P2: 34.8 ± 6.6 vs. NP: 11.9 ± 2.3), IL-1β (P2: 18.3 ± 0.8 vs. NP: 5.8 ± 2.2), TNF-α (P2: 23.5 ± 3.7 vs. NP: 8.3 ± 1.7) and elevated the expression levels of anti-inflammatory markers CD163 (P2: 19.7 ± 3.0 vs. NP: 41.1 ± 6.5; all for NP-PVA of 130 nm; relative to healthy control). These results highlight the therapeutic potential of such cargo-free NPs in treating EAN, which would be easily translatable into clinical use due to their well-known low-toxicity profile.

New Structural Nanocomposite Based on PLGA and Al2O3 NPs as a Balance between Antibacterial Activity and Biocompatibility with Eukaryotic Cells

Development of eco-friendly and biodegradable package materials is an important goal of modern science and international industry. Poly(lactic)-co-glycolic acid (PLGA) is suitable for this purpose. However, biocompatible materials may be contaminated with bacteria. This problem may be solved by the addition of metal oxides nanoparticles (NPs) with antibacterial properties. Although metal oxides NPs often show cytotoxicity against plant and mammalian cells, a new nanocomposite based on PLGA and aluminum oxide (Al2O3) NPs has been developed. The PLGA/Al2O3 NP composite has pronounced antibacterial properties. The addition of Al2O3 NPs 0.01% inhibited growth of E. coli for >50%. The antimicrobial effect of Al2O3 NPs is implemented through the generation of reactive oxygen species and damage of bacterial proteins and DNA. The biocompatibility of the nanocomposite with plant and mammalian cells was studied. The PLGA/Al2O3 NP composite did not influence the growth and development of tomatoes and cucumbers. PLGA and its composite with Al2O3 NPs 0.001–0.1% did not influence viability and proliferation of mammalian cells, on their density or substrate colonization rate. The developed nanocomposite has controlled mechanical properties, high antibacterial activity and high biocompatibility, which makes it an attractive candidate for building and food package material manufacture and agriculture.

The Role of Polylactic-Coglycolic Acid-Coated Electrospinning Nanoscaffold-Mediated Wnt/β-Catenin Signaling Pathway in Intervertebral Disc Degeneration and Its Relationship with Vitamin D Receptor

Using polyvinyl alcohol (PVA), polylactic coglycolic acid (PLGA), and transforming growth factor-β (TGF-β1) as raw materials, PLGA-coated electrospun nanoscaffold (ESNS) PVA-TGF-β1@PLGA was prepared by the coaxial ES method. Its characterization was analyzed by scanning electron microscopy (SEM), high-performance liquid chromatography (HPLC), and Fourier transform infrared spectroscopy (FTIR). Seventy-five healthy New Zealand rabbits were randomly rolled into the control group (no treatment, group C), model group (intervertebral disc degeneration (IDD) model, group M), and nanofiber scaffold group (implant PVA- TGF-β1@PLGA, group P). HE staining was adopted to visualize the histological morphology of the intervertebral disc (IVD) endplate in the different groups. Sox-9, Collagen type II, and Aggrecan genes in different groups of IVD endplate tissues were detected by qPCR. Vascular endothelial growth factor (VEGF), Wnt3α, β-catenin, glycogen synthase kinase-3β (GSK-3β), and vitamin D receptor (VDR) protein in IVD endplate tissues of different groups was detected by immunohistochemistry. IVD VDR protein and IDD-related protein levels were detected by Western blot. Linear trend tests and correlations were adopted to analyze the relationship between different degrees of IDD and VDR level. The results showed that the average particle size of the PVA-TGF-β1@PLGA NSs was approximately 415 nm, and Fourier infrared detection proved that PVA-TGF-β1@PLGA NSs were prepared. Sox-9, Collagen Type II, and Aggrecan gene levels in group M were notably inferior to those in group C (P < 0.05). Sox-9, collagen type II, and aggrecan gene levels in group P were substantially increased versus group M (P < 0.05). β-catenin level in groups P and M was greatly superior to that in group C (P < 0.05). GSK-3β and VEGF levels in group P were increased relative to group M (P < 0.05), while that of Wnt3α was decreased (P < 0.05). Western blotting confirmed that there was a negative relationship between the expression of IDD-related proteins and VDR. The results showed that PLGA-coated ESNS could promote Collagen II expression in the matrix of the nucleus pulposus (NP), reduce proteoglycan loss, and promote cell proliferation and differentiation by regulating the Wnt/β-catenin signaling pathway (Wnt/β Sig). VDR level was negatively correlated with the development of IDD in rats.

Formulation and In-vitro Antibacterial Activity of Gel containing Ethanolic extract of Purple Sweet Potato Leaves (Ipomoea batatas (L.) Loaded Poly Lactic Co-Glycolic Acid Submicroparticles against Staphylococcus aureus

Staphylococcus aureus has been resistant to various antibiotics including erythromycin, clindamycin, penicillin, trimethoprim-sulfamethoxazole, tetracyclines, chloramphenicol, and piperacillin-tazobactam so that an alternative treatment is needed. The purple sweet potato leaves (Ipomoea batatas (L.) Poir) contain flavonoid compounds that have antibacterial activity by inhibiting nucleic acid, protein synthesis, cell membrane, and energy metabolism in bacteria. In this study, ethanolic extract of purple sweet potato leaves is loaded to poly lactic-co-glycolic acid submicroparticles to increase the stability of flavonoids and the antibacterial effect. Submicroparticle gel was prepared with various concentrations of hydroxypropyl methylcellulose ie F1, F2, and F3 respectively 3%, 5%, and 7%. The antibacterial activity of submicroparticles gel compared with a gel containing extracts without submicroparticle and erythromycin gel as a positive control. Phytochemical test results that the ethanolic extract of purple sweet potato leaves contains flavonoids. Based on the research results, the best formula was F1(3%) with pH, homogeneity, viscosity, dispersibility, adhesion, and washability, respectively 7.4±0.0361; homogeneous; 8358.9±228.1391 cps; 4.2667±0.3005cm; 45.333±2.5166 seconds; 11.6667±1.5275mL. F1 was also shown to have strong antibacterial activity with an inhibition zone value of 13.67±4.04mm.

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic-co-glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incubating cell-particle mixture in methylcellulose solution while maintaining high cell viability. RAP-MPs were uniformly distributed in hybrid spheroids and sustainably released RAP for ~3 weeks. Locoregional transplantation of hybrid spheroids containing low doses of RAP-MPs (200- to 4000-ng RAP per recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced programmed death-ligand 1 expression by MSCs was found to be responsible for the immunomodulatory performance of hybrid spheroids. Our results suggest that these hybrid spheroids offer a promising platform for the efficient use of MSCs in the transplantation field.

PH-responsive albumin-coated biopolymeric nanoparticles with lapatinab for targeted breast cancer therapy

One can enhance the therapeutic index of anti-cancer drugs using albumin as a tumor homing agent for targeted cancer therapy. Herein, we sought to load lapatinib (LAPA) into small albumin-coated biopolymeric (poly-lactic co-glycolic acid (PLGA)) nanoparticles (APL NPs) by an emulsification method to improve the anti-tumor efficacy of lapatinib. The prepared APL NPs exhibited a small spherical core with an average diameter of 120.5±10.2nm with a narrow particle size distribution, high drug loading capacity (LC of 9.65±1.53%), good entrapment efficiency (EE of 75.55±3.25%), enhanced colloidal stability and a pH-responsive controlled drug release profile. Their cell-uptake and cancer cell growth inhibition were significantly higher compared to free LAPA and uncoated PLGA-LAPA (UPL) NPs, most likely because aggressive breast tumor cells over-express albumin receptors and utilize albumin as nutrient source for their growth. In addition, APL NPs possessed enhanced tumor accumulation and prolonged blood residence time compared to free LAPA and UPL NPs, allowing for potent tumor growth inhibition while exhibiting excellent biosafety. In short, the current study exploited a new and simple strategy to concurrently improve the safety and efficacy of LAPA for breast cancer treatment.

Hydrogel-Embedded Poly(Lactic-co-Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.

ObjectiveIntervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell–derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system.DesignWe characterize biophysical and biochemical properties of normoxic (Nx) and hypoxic (Hx) preconditioned MSC-Exos from young, healthy donors and examine their effects on AF cell proliferation, migration, and gene expression. We then integrate a poly(lactic-co-glycolic acid) microsphere (PLGA µSphere) delivery platform within an interpenetrating network hydrogel to facilitate sustained MSC-Exo delivery.ResultsHx MSC-Exos led to a more robust response in AF cell proliferation and migration than Nx MSC-Exos and was selected for a downstream protection experiment. Hx MSC-Exos maintained a healthy AF cell phenotype under a TNFα challenge in vitro and attenuated catabolic responses. In all functional assays, AF cell responses were more sensitive to Hx MSC-Exos than Nx MSC-Exos. PLGA µSpheres released MSC-Exos over a clinically relevant timescale without affecting hydrogel modulus or pH upon initial embedment and µSphere degradation.ConclusionsThis MSC-Exo treatment strategy may offer benefits of stem cell therapy without the need for exogenous stem cell transplantation by stimulating cell proliferation, promoting cell migration, and protecting cells from the degenerative proinflammatory microenvironment.

Development and Validation of UV-spectrophotometric Method for Estimation of Berberine Hydrochloride in Marketed Formulation and Poly Lactic Co-glycolic Acid Nanoparticles

Development and Validation of UV-spectrophotometric Method for Estimation of Berberine Hydrochloride in Marketed Formulation and Poly Lactic Co-glycolic Acid Nanoparticles

Biodegradable nanoparticle-induced sting pathway activation for the treatment of cancer.

e14552 Background: Recent advances in the field of cancer immunology have highlighted the importance of the immune system for eliminating tumors. Numerous studies have shown that tumor-infiltrating immune cells such as antigen-presenting cells (APCs), T cells, and natural killer (NK) cells play critical roles in tumor control. However, the inflammatory anti-tumor immune response is counteracted by the induction of immune regulatory mechanisms within the tumor microenvironment (TME). These findings have led to the development of immune-targeted therapies, which are aimed at activating anti-tumor immune signaling pathways and enhancing anti-tumor immune function. While immunotherapies, have revolutionized the treatment of several solid tumors and leukemias, at best response rates remain low at 25%-30%, and a portion of patients eventually develop resistance to therapy leading to disease progression and mortality. Methods: We have previously reported the potent effects of 3-4 daily intravenous infusions of immune modifying poly(lactic- co-glycolic acid) (PLGA) nanoparticles, ONP-302, free from drugs or other bioactive agents, for the amelioration of acute inflammatory diseases by targeting myeloid cells. The present studies describe a novel use for ONP-302 nanoparticles, employing an altered dosing scheme to reprogram myeloid cells resulting in significant enhancement of tumor immunity. The efficacy of ONP-302 nanoparticles at inducing an anti-tumor immune response was evaluated using syngeneic mouse tumor models. Results: ONP-302 infusion decreased tumor growth via the activation of the cGAS/STING pathway within myeloid cells, and subsequently increased NK cell activation via an IL-15-dependent mechanism. Additionally, ONP-302 treatment increased PD-1/PD-L1 expression in the tumor microenvironment, thereby allowing for functionality of anti-PD-1 for treatment in the B16.F10 melanoma tumor model which is normally unresponsive to monotherapy with anti-PD-1. Conclusions: These findings indicate that ONP-302 allows for tumor control via reprogramming myeloid cells via activation of the STING/IL-15/NK cell mechanism, as well as increasing anti-PD-1 response rates.

Nano-based targeted drug delivery for lung cancer: therapeutic avenues and challenges.

Most anticancer drugs often fail in clinical trials due to poor solubility, poor bioavailability, lack of targeted delivery and several off-target effects. Polymeric nanoparticles such as poly(lactide), poly(lactic-co-glycolic acid), ALB-loading paclitaxel (Abraxane® ABI-007), lomustine-loaded chitosan, gelatin (decorated with EGF receptor-targeted biotinylated EGF) and so on offer controlled and sustained drug-release properties, biocompatibility and promising anticancer effects. EGF, folic acid, transferrin, sigma and urokinase plasminogen activator receptors-targeting nano preparations improve bioavailability and accumulate drugs on the lung tumor cell surface. However, route of administration, size, pharmacokinetic properties, immune clearance and so on hamper nanomedicines' clinical uses. This review focuses on the benefits, avenues and challenges of nanoparticle-based drug-delivery systems for lung cancer treatment.

Investigation of the drug release time from the biodegrading coating of an everolimus eluting stent.

This case-study examines the release time of the everolimus drug from an experimental biodegrading coating of a Rontis corp. drug eluting stent (DES). The controlled drug release is achieved by the degradation of the coating, which consists of a mixture of polylactic co-glycolic acid (PLGA) and everolimus (55:45). In our analysis, we used the outcome of another study, which contains the geometry of an in-silico deployed Rontis corp. stent in a 3D reconstructed coney arterial segment. Using this geometry as input, the everolimus release was simulated using a computational model that includes: i) modeling of the blood flow dynamics, ii) modeling of PLGA degradation, and iii) modeling of the everolimus advection and diffusion towards both the lumen and the arterial wall. The results show the rapid release of everolimus. This is justified due to the high porosity of the coating, which is caused by the initial high concentration of everolimus in the coating.Clinical Relevance - The methodology presented in this work is an additional step towards predicting accurately drug release from DES. Also, the results of our work prove that high drug concentration in the coating causes its rapid release, which could be used as input in the design of new DES.