Tuesday, November 29, 2016

PLGA from PolySciTech used as part of macrophage-targeted protein delivery system

Despite the development of many protein-based, or biologic, medicines their application has been limited due to difficulty in administration. An attractive target for medicinal delivery is macrophage cells, immune cells which attack foreign materials and pathogens, as the action, or inaction, of these cells are involved in many diseases. Recently, researchers at Kangwon National University in Korea utilized PLGA from PolySciTech (www.polyscitech.com) to deliver protein-based drugs to macrophages. Acid ended PLGA from PolySciTech (PolyVivo AP081) was conjugated to dopamine to form a nanoparticle which targeted towards macrophage cells.  This particle was found to be able to deliver a model protein (albumin) to these cells with high uptake. This research holds promise for treating a wide variety of diseases ranging from inflammatory disease to cancers. Read more:  Lee, Song Yi, and Hyun-Jong Cho. "Dopamine-conjugated poly (lactic-co-glycolic acid) nanoparticles for protein delivery to macrophages." Journal of Colloid and Interface Science (2016). http://www.sciencedirect.com/science/article/pii/S0021979716309559

“Abstract: Poly(lactic-co-glycolic acid)-dopamine (PLGA-D)-based nanoparticles (NPs) were developed for the delivery of protein to macrophages. PLGA-D was synthesized via amide bond formation between the –NH2 group of D and the –COOH group of PLGA. Bovine serum albumin (BSA, model protein) was encapsulated in PLGA NPs and PLGA-D NPs, which had an approximately 200 nm mean diameter, < 0.2 polydispersity index, and negative zeta potential value. There was no increment in the mean diameters of BSA-loaded NPs after 24 h of incubation in biological fluid-simulated media (i.e., aqueous buffer and serum media). The primary, secondary, and tertiary structures of BSA released from the NPs were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDSPAGE), circular dichroism, and fluorescence spectrophotometry; the structural stability of BSA was preserved during its encapsulation in the NPs and release from the NPs. PLGA/BSA NPs and PLGA-D/BSA NPs did not induce serious cytotoxicity in RAW 264.7 cells (mouse macrophage cell line) in an established concentration range. In RAW 264.7 cells, the intracellular accumulation of PLGA-D NPs was 2-fold higher than that of PLGA NPs. All of these findings indicated that PLGA-D NPs are a promising system for delivering proteins to macrophages. Keywords: dopamine; macrophage; nanoparticles; PLGA; protein”

Tuesday, November 22, 2016

PLGA-PEG-COOH precursor from PolySciTech used as part of development of brain-cancer targeting nanoparticle

One attractive aspect for treatment for cancer is ‘theranostics.’ Theranostics represents a combination of ‘thera’py and diag’nostics.’ The goal for this is to both treat the cancer therapeutically as well as apply an agent to render it more detectable so as to assist in either surgical removal or monitoring of progress. Recently, researchers utilized the precursor PLGA-PEG-COOH from PolySciTech (www.polyscitech.com) (PolyVivo AI076) as part of developing an aptamer decorated nanoparticle. The nanoparticle contained both superparamagnetic iron oxide nanocrystals, an MRI contrast agent, and doxorubicin, a chemotherapeutic agent. The formed nanoparticles were found to have good uptake towards glioma cells indicating their potential for theranostic applications towards brain cancer. This research holds promise for improved therapy of brain cancer. Read more: Mosafer, Jafar, Manouchehr Teymouri, Khalil Abnous, Mohsen Tafaghodi, and Mohammad Ramezani. "Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells." Materials Science and Engineering: C (2016). http://www.sciencedirect.com/science/article/pii/S0928493116322068

“Highlights: Dox-containing PLGA-nanoparticle improves cancerous cytotoxicity of free Dox. Anti-nucleolin aptamer-nanoparticle leads to targeted cell delivery of drug. SPION containing PLGA-nanoparticle is apt for imaging purposes of tumors. PLGA releases doxorubicin inside cells, not outside the cells. PLGA could lead to improved drug retention in serum. Abstract: Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA 1) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs2) and doxorubicin (Dox3) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs4 were conjugated to anti-nucleolin AS1411 aptamer (Apt5) and their targeting ability was investigated in high nucleolin-expressing C6 glioma cells compared to low nucleolin-expressing L929 cells. The NPs exhibited a narrow size distribution with mean diameter of ~ 170 nm and an appropriate SPION content (~ 18% of total polymer weight) with a sufficient saturation magnetization value of 5.9 emu/g which is suitable for imaging objectives. They manifested an increased Dox release at pH 5.5 compared to pH 7.4, with initial burst release (within 24 h) followed by sustained release of Dox for 36 days. The Apt conjugation to NPs enhanced cellular uptake of Dox in C6 glioma cells compared to L929 cells. Similarly, the Apt-NPs increased the cytotoxicity effect of Dox compared with NPs and Dox solution (f-Dox) alone. In conclusion, the Apt-NPs were found to be a promising delivery system for therapeutic and diagnostic purposes. Keywords: SPION; Doxorubicin; Glioma cell; Nucleolin; PLGA; Aptamer”

Monday, November 21, 2016

PLGA from PolySciTech used in development of vaccine nanoparticle for improved efficacy

In the field of vaccines, occasionally the application of the antigen alone is not enough to induce a full immune response. In this case, an adjuvant or delivery system is utilized in order to improve the immune response. Recently, researchers utilized PolySciTech (www.PolySciTech.com) PLGA (75:25) (PolyVivo cat# AP054) for developing a nanoparticle for enhancing vaccine performance. This research holds promise for improved development of vaccines that result in a strong immune response to prevent future infections. Read more: Guldner, Delphine, Julianne K. Hwang, Maria Clara D. Cardieri, Meaghan Eren, Parissa Ziaei, M. Grant Norton, and Cleverson D. Souza. "In Vitro Evaluation of the Biological Responses of Canine Macrophages Challenged with PLGA Nanoparticles Containing Monophosphoryl Lipid A." PloS one 11, no. 11 (2016): e0165477 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165477

“Abstract: Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been considerably studied as a promising biodegradable delivery system to induce effective immune responses and to improve stability, safety, and cost effectiveness of vaccines. The study aimed at evaluating early inflammatory effects and cellular safety of PLGA NPs, co-encapsulating ovalbumin (PLGA/OVA NPs), as a model antigen and the adjuvant monophosphoryl lipid A (PLGA/MPLA NPs) as an adjuvant, on primary canine macrophages. The PLGA NPs constructs were prepared following the emulsion-solvent evaporation technique and further physic-chemically characterized. Peripheral blood mononuclear cells were isolated from canine whole blood by magnetic sorting and further cultured to generate macrophages. The uptake of PLGA NP constructs by macrophages was demonstrated by flow cytometry, transmission electron microscopy and confocal microscopy. Macrophage viability and morphology were evaluated by trypan blue exclusion and light microscopy. Macrophages were immunophenotyped for the expression of MHC-I and MHC-II and gene expression of Interleukin-10 (IL-10), Interleukin-12 (IL-12p40), and tumor necrosis factor alpha (TNF-α) were measured. The results showed that incubation of PLGA NP constructs with macrophages revealed effective early uptake of the PLGA NPs without altering the viability of macrophages. PLGA/OVA/MPLA NPs strongly induced TNF-α and IL-12p40 expression by macrophages as well as increase relative expression of MHC-I but not MHC-II molecules. Taken together, these results indicated that PLGA NPs with addition of MPLA represent a good model, when used as antigen carrier, for further, in vivo, work aiming to evaluate their potential to induce strong, specific, immune responses in dogs.”

Wednesday, November 16, 2016

PolySciTech PLGA-rhodamine used as part of lung nanoparticle delivery research

One pathway for medicinal delivery is inhalation which exposes lung tissues to the inhaled substance. Nanoparticles can also be applied this way as they are small enough to disperse in air and allow for uptake by breathing. Recently, researchers utilized PLGA-rhodamine (PolyVivo Cat# AV011) from PolySciTech (www.polyscitech.com) in order to render their surface-decorated nanoparticles fluorescent to enable tracking of the particle uptake and fate. This research holds promise for elucidating the mechanisms of lung-uptake of inhaled nanoparticles. Read more: Ruge, Christian Arnold, Herve Hillaireau, Nadege Grabowski, Moritz Beck-Broichsitter, Olga Canadas, Nicolas Tsapis, Cristina Casals, Julien Nicolas, and Elias Fattal. "Pulmonary Surfactant Protein A–Mediated Enrichment of Surface-Decorated Polymeric Nanoparticles in Alveolor Macrophages." Molecular Pharmaceutics (2016). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00773

“Abstract: Surfactant protein A (SP-A), a lung anti-infective protein, is a lectin with affinity for sugars found on fungal and micrococcal surfaces such as mannose. We synthesized a mannosylated poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) co-polymer and used it to produce nanoparticles with a polyester (PLGA/PLA) core and a PEG shell decorated with mannose residues, designed to be strongly associated with SP-A for an increased uptake by alveolar macrophages. Nanoparticles made of the co-polymers were obtained by nanoprecipation and displayed a size of around 140 nm. The presence of mannose on the surface was demonstrated by zeta potential changes according to pH and by a strong aggregation in the presence of concanavalin A. Mannosylated nanoparticles bound to SP-A as demonstrated by dynamic light scattering and transmission electron microscopy. The association with SP-A increased nanoparticle uptake by THP-1 macrophages in vitro. In vivo experiments demonstrated that after intratracheal administration of nanoparticles with or without SP-A, SP-A-coated mannosylated nanoparticles were internalized by alveolar macrophages in greater proportion than SP-A-coated non-mannosylated nanoparticles. The data demonstrate for the first time that the pool of nanoparticles available to lung cells can be changed after surface modification, using a biomimetic approach.”

Tuesday, November 15, 2016

PLGA from PolySciTech used as part of vaccine-delivery system for protection against deadly Group-A strep

Group-A Streptococcus is a bacterial infection which causes over 500,000 deaths/year worldwide. Depending on location of infection, this bacteria can cause diseases including osteomyelitis, necrotizing fasciitis, strep throat, and others. In most cases antibiotics can work to control the infection however with increasing resistance there is a need for a vaccine to effectively prevent the infection in the first place. Recently, researchers utilized PLGA (PolyVivo Cat# AP041) from PolySciTech: Akina, Inc. (www.polyscitech.com) as part of intra-nasal, nanoparticle-based delivery system for a group-A streptococcus peptide vaccine. They tested the system in animal model and found that the produced antibodies were effective against GAS. This research holds promise for the development of an effective vaccine against this deadly disease. Read more: Marasini, Nirmal, Ashwini K. Giddam, Zeinab G. Khalil, Waleed M. Hussein, Robert J. Capon, Michael R. Batzloff, Michael F. Good, Istvan Toth, and Mariusz Skwarczynski. "Double adjuvanting strategy for peptide-based vaccines: trimethyl chitosan nanoparticles for lipopeptide delivery." Nanomedicine 00 (2016). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2016-0291

“Aim: To develop novel polymer-based nanoscale delivery system for lipopeptide-based vaccine against group A Streptococcus (GAS). Materials & methods: Four types of lipopeptide antigen-loaded polymeric nanoparticles (NP) were prepared. NP were accessed for their capacity to be taken up by dendritic cells; effect on dendritic cell maturation; ability to induce mucosal and systemic immunity; and capability to induce antibody responses that opsonize GAS bacteria. Results & discussion: The combination of adjuvanting properties of lipopeptides and dextran/trimethyl chitosan-based NP had a synergistic effect on humoral immunity, and the produced antibodies showed high opsonic activity against clinical GAS isolates. Conclusion: Biocompatible NP-bearing trimethyl chitosan and dextran are efficient as mucosal adjuvants for the intranasal delivery of lipopeptide-based vaccines.”

PEG-PLGA and mal-PEG-PLGA from PolySciTech used in the development of a bone-specific nanoparticle system for drug delivery to skeletal tissue.

Due to skeletal-tissue’s anatomical features and high mineral content, delivery of medicines to bone tissue has remained difficult to achieve. This makes treatment of bone diseases (bone cancer, rickets, osteoporosis and others) especially difficult as the majority of administered medicine is excreted without achieving therapeutic effect. Recently, researchers at University of Connecticut and University of Wisconsin-Madison used PolySciTech Mal-PEG-PLGA (PolyVivo cat# AI020) and methoxy-PEG-PLGA (PolyVivo cat# AK037) to formulate drug-delivery nanoparticles and conjugated to these aspartic acid as a targeting moiety. They found that the developed system provided for efficient targeting to bone tissue. This research holds promise for treating a wide array of bone diseases. Carbone, Erica J., Komal Rajpura, Tao Jiang, Ho-Man Kan, Xiaohua Yu, and Kevin W-H. Lo. "Osteotropic Nanoscale Drug Delivery System via a Single Aspartic Acid as the Bone-Targeting Moiety." Journal of Nanoscience and Nanotechnology 17, no. 3 (2017): 1747-1752. http://www.ingentaconnect.com/contentone/asp/jnn/2017/00000017/00000003/art00029

“Abstract: Osteotropic nanoparticle-based drug delivery systems have been investigated as potential therapies for various skeletal diseases. These delivery systems are usually formulated by functionalizing the nanoparticle surfaces with bone-targeting ligands. Antibodies, proteins or peptide sequences have shown promise as bone-targeting ligands; however, methods utilizing these targeting ligands suffer from many limitations including high production cost, protein or peptide instability, and unwanted immune response. These limitations can be minimized by using the osteotropic small molecule approach because of the stability, ease of conjugation with polymeric nanoparticles, and low cost of small molecules. We, and others, have previously demonstrated that poly-aspartic acid sequencelinked biodegradable polymeric nanoparticles can interact specifically with mineralized tissue in vitro, ex vivo, and in vivo. The hypothesis of this study is that single aspartic acid-linked nanoparticles can effectively interact with bone tissue specifically. In this study, we sought to identify the minimal aspartic acid residues stretch necessary for efficient HA binding. We further sought to design a novel osteotropic nanoparticle-based drug delivery system using a single aspartic acid small molecule as the bone-targeting moiety. Keywords: Musculoskeletal Tissue; Nanomedicine; Small Molecules; Targeted Drug Delivery; Targeting Ligands”

Monday, November 14, 2016

Purdue nanoHUB details Akina’s 3DCellMaker

The PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of research products including 3DCellmaker for culturing of cells in a three-dimensional structure. 3DCellMaker is a widely applicable thermogel-based cell-growth platform which enables 3D culture of cell structures. Purdue University’s latest nanoHUB newsletter article (https://nanohub.org/groups/3d3cfacility/news#threedpurdue) discusses 3DCellMaker for cell growth. 

“Culturing cells in 3D structures provides many advantages over 2D models. Cells in 3D structures often behave differently from those in 2D cultures. For example, cancer cells organized in 3D spheroids are often more resistant to anticancer drugs than cells in 2D cultures. Several types of commercially available products allow researchers to produce multicellular spheroids. The products are classified into (i) extracellular matrices based on cellular extracts, (ii) natural polymers, and (iii) cell culture plates with non-cell adherent surface or with no surface for the cells to attach. Each method has its own advantages and limitations. Recently, we developed simple polymeric systems that allow cells to form 3D structures. The polymers are named “3DCellMaker” for its ability to culture various types of cells and cell mixtures in 3D. 3DCellMakers are inverse themosensitive gels (thermogels), i.e., they remain in liquid form at room temperature or lower and become a gel at 37 °C. These thermogels are poloxamers-poly(ester-urethane) copolymers or stearate-modified methyl cellulose. For the culture process, the cells can be placed on top of the formed gels, or they can be mixed with the thermogels at low temperature before incubating at 37 °C. The simplicity, and low cost, of using 3DCellMaker allows culturing of various cell types in 3D for high throughput screening. The synthetic nature of the 3DCellMaker makes it easy to control the gel’s properties. The 3DCellMaker also allows culture of cells with defined additives, under serum-free conditions. 3DCellMaker thermogels are available for free for researchers at Purdue University.”