Tuesday, March 28, 2017

mPEG-PCL from PolySciTech utilized in development of Chrysin-nanoparticle based therapy for lung-cancer


Lung cancer is among the leading causes of cancer-related death worldwide. Chrysin, a natural active flavone, acts to enhance the chemotherapeutic effectiveness of other chemoagents (cisplatin, docetaxel, etc.) against lung cancer. Chrysin’s usability, however, is limited by its very poor water solubility and low bioavailability. Recently, researchers at Duksung Women’s University (Korea) utilized mPEG-PCL from PolySciTech (www.polyscitech.com) (PolyVivo #: AK001) to formulate chrysin-loaded nanoparticles which were found to delay tumor progression in a mouse model. This research holds promised for improved lung-cancer therapy. Read more: Kim, Kyoung Mee, Hyun Kyung Lim, Sang Hee Shim, and Joohee Jung. "Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles." International Journal of Nanomedicine 12 (2017): 1917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352247/


“Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model. Nanoparticle preparation method: Chrysin (Sigma-Aldrich, St Louis, MO, USA) was incorporated into copolymer NPs using an oil-in-water technique (Figure 1). mPEG–β-polycaprolactone copolymer (mPEG-PCL, 50 mg; 2,000:5,200 Da; PolySciTech, West Lafayette, IN, USA) and 5 mg of chrysin were dissolved in a dichloromethane (Duksan reagent, Gyeonggi-do, Korea) and methanol mixture (Duksan reagent; v/v, 1.5:1). This solution (2.5 mL) was added to a 1% aqueous polyvinyl alcohol solution (6 mL) and was emulsified by sonification for 1 min. The solvent was removed by evaporation under stirring to produce NPs. To remove polyvinyl alcohol and surplus free chrysin, the supernatant was collected after centrifugation (14,000 rpm) twice at room temperature for 1 h.”

Monday, March 27, 2017

T-shirt

PolySciTech: Keeping scientists and engineers fashionably dressed since 2013.  (www.polyscitech.com, free t-shirt with select orders)


Wednesday, March 22, 2017

PLGA from PolySciTech used in optimizing 3D printing techniques for tissue engineering

A relatively recent and powerful tool for both manufacturing and research has been developed in 3D printing. Despite it’s advantages, 3D printing is restricted based on the polymeric material’s melt and processing properties. Recently, researchers working jointly at University of Maryland, Cornell University, and Rice University screened through a series of PLGA materials in order to define the optimal printing procedures for each. The utilized a series of PLGA’s from PolySciTech (www.polyscitech.com) (PolyVivo AP039, AP137, AP076, and AP024) and optimized their printing configurations for bone-tissue engineering. This research holds promise for the capability to print biocompatible, biodegradable parts for tissue engineering and other applications. Read more at: Guo, Ting, Timothy Holzberg, Casey Lim, Feng Gao, Ankit Gargava, Jordan Trachtenberg, Antonios Mikos, and John Fisher. "3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution." Biofabrication (2017). http://iopscience.iop.org/article/10.1088/1758-5090/aa6370/meta

“Abstract: In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meets patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography (microCT) was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.”


Friday, March 17, 2017

PLGA-PEG-COOH from PolySciTech used in development of ultra-sound triggered breast cancer theranostic nanoparticles

One of the goals within controlled delivery is to provide for targeted medicinal delivery in which the medicine is guided to the site that it is needed in by natural processes. More specifically, in cancer, there is a need to delivery nanoparticles to the tumor site for both therapy (medicinal delivery) as well as diagnosis (contrast agent delivery) Recently, researchers at Chongqing Medical University (China) used PolySciTech (www.polyscitech.com) product PLGA-PEG-COOH (PolyVivo AI056) and conjugated on Herceptin (antibody which conjugates to breast cancer tumors) to target it towards breast cancer cells. They formulated these with both contrast agents and chemotherapeutic paclitaxel. This research holds promise for improved breast-cancer therapy. Read more: Song, Weixiang, Yindeng Luo, Yajing Zhao, Xinjie Liu, Jiannong Zhao, Jie Luo, Qunxia Zhang, Haitao Ran, Zhigang Wang, and Dajing Guo. "Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study." Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0027


“Aim: The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. Materials & methods: Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. Results: PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. Conclusion: These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.”

Wednesday, March 15, 2017

PolySciTech mPEG-PLGA and PLGA-Rhodamine products used in development of advanced chemoradiotherapy delivery system

Chemoradiotherapy is a cancer therapy technique in which a sensitizer molecule is administered to a patient prior to administration of a dose of radiation. Typically, such a technique is made difficult as the sensitizer molecule can affect both tumor tissue and normal tissue, causing more damage from radiation. However, with the application of localized-delivery to the tumor, this technique holds great potential for cancer therapy by allowing specific and selective destruction of tumor tissue at a relatively lower dose of radiation.  Recently, researchers at the University of North Carolina Chapel Hill utilized PolySciTech (www.polyscitech.com) mPEG-PLGA’s (PolyVivo AK010, AK023) and fluorescently-tagged polymer PLGA-rhodamine B (PolyVivo AV011) for development of an advanced nanoparticle delivery system for Wortmannin (DNA-PK inhibitor) or novel KU60019 (ATM inhibitor) molecules. Both of these molecules act to increase local radiation damage to tumors by preventing DNA repair. The researchers found that smaller particles were more effective at avoiding hepatic clearance but medium sized particles showed more efficacy for sensitization. This research holds promise for enhanced cancer treatment techniques. Read more: Caster, Joseph M., K. Yu Stephanie, Artish N. Patel, Nicole J. Newman, Zachary J. Lee, Samuel B. Warner, Kyle T. Wagner et al. "Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy." Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300448

“Abstract: Nanoparticle (NP) therapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend towards enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application. Graphical Abstract: Sub50 nm drug-loaded NPs avoid hepatic clearance and more homogeneously distribute within tumors. However, they are no more efficacious and are associated with more small bowel toxicity than larger particles. Keywords: Nanoparticle; Chemoradiotherapy; Nanoparticle radiosensitization; KU60019; Wortmannin”


Parkinson’s disease treatment developed using mPEG-PLGA block copolymer for neuroprotective agent delivery

Parkinson’s disease is a chronic, neural-degenerative which affects motor control and other operations of the nervous system eventually leading to death. Schisantherin A is a recently discovered neuroprotective agent which acts to inhibit damage to neural cells and can be used to slow the progression of Parkinson’s disease (https://www.ncbi.nlm.nih.gov/pubmed/25770828). It has severe limitations, however, as it is poorly soluble in water and quickly cleared from the blood-stream.  Schisantherin A , like many neurological medicines, also faces the severe impediment of the blood-brain-barrier. This barrier which exists between circulating blood and brain tissue is intended to protect the brain from any toxic components that may be in the blood but also serves the unintentional purpose of preventing uptake of medicinal components into the brain tissue.  Recently, researchers at University of North Carolina at Chapel Hill and University of Macau utilized mPEG-PLGA to generate small-sized nanoparticles containing Schisantherin A. They found these nanoparticles to improve serum circulation longevity and uptake across the blood-brain-barrier. This research holds promise for enhanced therapy against this fatal disease. Similar block copolymers can be purchased from PolySciTech division of Akina, Inc. (www.polyscitech.com). Read more about this exciting research here: Chen, Tongkai, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, and Ying Zheng. "Small-Sized mPEG–PLGA Nanoparticles of Schisantherin A with Sustained Release for Enhanced Brain Uptake and Anti-Parkinsonian Activity." ACS Applied Materials & Interfaces (2017). http://pubs.acs.org/doi/abs/10.1021/acsami.7b01171

“Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson’s disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG–PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of 91% and drug loading of 28%. The in vitro release of the SA-NPs lasted for 48 h with a sustained-release pattern. Using the Madin–Darby canine kidney (MDCK) cell model, the results showed that first intact nanoparticles carrying hydrophobic dyes were internalized into cells, then the dyes were slowly released within the cells, and last both nanoparticles and free dyes were externalized to the basolateral side of the cell monolayer. Fluorescence resonance energy transfer (FRET) imaging in zebrafish suggested that nanoparticles were gradually dissociated in vivo with time, and nanoparticles maintained intact in the intestine and brain at 2 h post-treatment. When SA-NPs were orally administrated to rats, much higher Cmax and AUC0-t were observed in the plasma than those of the SA suspension. Furthermore, brain delivery of SA was much more effective with SA-NPs than with SA suspension. In addition, the SA-NPs exerted strong neuroprotective effects in zebrafish and cell culture models of PD. The protective effect was partially mediated by the activation of the protein kinase B (Akt)/glycogen synthase kinase-3β (Gsk3β) pathway. In summary, this study provides evidence that small-sized mPEG–PLGA nanoparticles may improve cross-barrier transportation, oral bioavailability, brain uptake, and bioactivity of this Biopharmaceutics Classification System (BCS) Class II compound, SA. Keywords: brain delivery; cellular uptake; fluorescence resonance energy transfer (FRET); mPEG−PLGA nanoparticles; oral bioavailability; Schisantherin A”


Monday, March 6, 2017

PLGA-PEG-Maleimide from PolySciTech used in development of macular degeneration treatment

One of the causes of ocular damage which can lead to blindness is choroidal neovascularization, effectively the over-growth of new blood vessels in the back of the eye. This condition is involved in the development of age-related macular degeneration which can lead to blindness. Recently, researchers at Yantai University (China) utilized Mal-PEG-PLGA (PolyVivo AI020) from PolySciTech (www.polyscitech.com) to develop RGD and TAT peptide modified nanoparticles to deliver therapeutics to ocular tissues as part of treatment of macular degeneration. This research holds promise to provide treatment for a disease which causes blindness. Read more: Chu, Yongchao, Ning Chen, Huajun Yu, Hongjie Mu, Bin He, Hongchen Hua, Aiping Wang, and Kaoxiang Sun. "Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles." International Journal of Nanomedicine 12 (2017): 1353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325139/

“Abstract: A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. Keywords: nanoparticles, ocular drug delivery, choroidal neovascularization, RGD, cell-penetrating peptides. Method for iRGD Conjugation: Briefly, Mal–PEG–PLGA was dissolved in acetone and the organic solvent then evaporated, dispersing the solute evenly on the flask wall. The flask was replenished with 0.01 M phosphate-buffered saline (PBS, pH 7.4) and left overnight to react with iRGD. The iRGD was conjugated to Mal–PEG–PLGA (at 4°C, at a 1:1 molar ratio of peptide to Mal–PEG–PLGA).”