John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


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Thermogel PLGA-PEG-PLGA from PolySciTech used in development of minimally invasive liver-cancer microwave ablation therapy

Monday, February 27, 2017, 5:05 PM ET

Recently, researchers have developed improvements in the localization and effectiveness of Microwave Ablation therapy by combining PolySciTech Division of Akina, Inc. (www.polyscitech.com) thermogelling product (PLGA-PEG-PLGA PolyVivo, Cat# AK088) with non-radioactive Cesium chloride to create an injectable thermal accelerant. This research holds promise for improved ablation treatment of liver cancer. Read more: Park, William Keun Chan, Aaron Wilhelm Palmer Maxwell, Victoria Elizabeth Frank, Michael Patrick Primmer, Scott Andrew Collins, Grayson Luderman Baird, and Damian Edward Dupuy. "Evaluation of A Novel Thermal Accelerant For Augmentation Of Microwave Energy During Image-guided Tumor Ablation." Theranostics, in print (2017). http://www.thno.org/v07p1026.pdf

“The primary challenge in thermal ablation of liver tumors (e.g. hepatocellular carcinoma and hepatic colorectal cancer) is the relatively high recurrence rate (~30%) for which incomplete ablation at the periphery of the tumor is the most common reason. In an attempt to overcome this, we have developed a novel thermal accelerant (TA) agent capable of augmenting microwave energy from a distance normally unattainable by a single microwave ablation antenna. This cesium-based block co-polymer compound transforms from a liquid to a gel at body temperature and is intrinsically visible by computed tomography. Using an agarose phantom model, herein we demonstrate that both the rate and magnitude of temperature increase during microwave ablation were significantly greater in the presence of TA when compared with controls. These results suggest robust augmentation of microwave energy, and may translate into larger ablation zone volumes within biologic tissues. Further work using in vivo techniques is necessary to confirm these findings. Key words: Image-guided thermal ablation, microwave ablation, thermal accelerant, augmentation of microwave energy, non-radioactive cesium chloride, block-co-polymer, PLGA-PEG-PLGA, dipole moment, complex dielectric permittivity, dielectric constant, loss factor.”

New whitepaper on thermogelling PLCL-PEG-PLCL aqueous storage stability as a ready-to-go solution

Wednesday, February 22, 2017, 11:51 AM ET

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers. One class of these is thermogelling polymers which can dissolve in cold water and then form into a solid gel once the water is warmed above the LCST. In some situations, one may want to dissolve the polymer in an aqeous solution and then store it in this ready-to-go condition for some time prior to use. As these polymers are hydrolysable, there is a finite span of time that this gel solution can be stored. Recently, accelerated degradation testing was performed using PLCL-PEG-PLCL PolyVivo AK109. The PLCL blocks provide for slower degradation as compared with PLGA blocks and this study was designed to see how long these thermogels can be store. You can see more on this here (http://akinainc.com/pdf/AK109%20storage%20stability.pdf)

mPEG-PLA from PolySciTech used as part of SPION-methicillin loaded nanoparticle development for eradication of drug-resistant bacterial biofilms

Tuesday, February 21, 2017, 10:34 AM ET

There is increasing prevalence of bacterial resistance towards antibiotics due to genetic as well as structural changes. Notably, certain types of bacteria tend to form into tight biofilms which are surrounded by a protective matrix that reduces antibiotic infiltration. These biofilms can be up to 1000 times more resistant towards conventional antibiotics than loose bacteria and account for up to 60% of all infectious diseases in the western world. Recently, researchers at Northeastern University utilized mPEG-PLA (PolyVivo cat# AK021) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to co-encapsulate iron-oxide particles and methicillin inside polymeric nanoparticles. They discovered that these nanoparticles, under a magnetic field, were able to penetrate deep into staph-bacteria biofilms and kill the bacteria, while having no toxicity towards mammalian cells. This research holds promise for providing advanced treatment options of drug-resistant bacteria and infections at medical implant surfaces. Read more: Geilich, Benjamin M., Ilia Gelfat, Srinivas Sridhar, Anne L. van de Ven, and Thomas J. Webster. "Superparamagnetic iron oxide-encapsulating polymersome nanocarriers for biofilm eradication." Biomaterials 119 (2017): 78-85. http://www.sciencedirect.com/science/article/pii/S0142961216307086

“Abstract: The rising prevalence and severity of antibiotic-resistant biofilm infections poses an alarming threat to public health worldwide. Here, biocompatible multi-compartment nanocarriers were synthesized to contain both hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and the hydrophilic antibiotic methicillin for the treatment of medical device-associated infections. SPION co-encapsulation was found to confer unique properties, enhancing both nanocarrier relaxivity and magneticity compared to individual SPIONs. These iron oxide-encapsulating polymersomes (IOPs) penetrated 20 μm thick Staphylococcus epidermidis biofilms with high efficiency following the application of an external magnetic field. Three-dimensional laser scanning confocal microscopy revealed differential bacteria death as a function of drug and SPION loading. Complete eradication of all bacteria throughout the biofilm thickness was achieved using an optimized IOP formulation containing 40 μg/mL SPION and 20 μg/mL of methicillin. Importantly, this formulation was selectively toxic towards methicillin-resistant biofilm cells but not towards mammalian cells. These novel iron oxide-encapsulating polymersomes demonstrate that it is possible to overcome antibiotic-resistant biofilms by controlling the positioning of nanocarriers containing two or more therapeutics. Keywords: Biofilm; Polymersome; SPION; Staphylococcus epidermidis; Antibiotic-resistance; Nanomedicine”

Akanocure Press Release

Tuesday, February 7, 2017, 3:18 PM ET

You can obtain commercially available Akanocure products at https://akinainc.com/polyscitech/products/akanocure/index.php read more in a a recent press release regarding Akanocure is available here http://www.purdue.edu/newsroom/releases/2017/Q1/purdue-affiliated-pharmaceutical-company-launches-product-to-produce-rare-disease-fighting-compounds.html

Amine-endcap PLGA from PolySciTech used in development of heart-attack treatment

Tuesday, February 7, 2017, 12:51 PM ET

Heart attack, or myocardial infarction, is the leading cause of death worldwide. One of the causes of tissue damage which occurs during a heart attack is excess calcium influx that occurs once blood-flow is reestablished (reperfusion). This calcium influx leads to cell death and massive tissue damage to the heart muscles rendering them inoperable which can be lethal for the patient. Recently, researchers working jointly at University of Iowa and Mahidol University (Thailand), utilized PLGA-NH2 from PolySciTech division of Akina, Inc. (www.polyscitech.com) (PolyVivo AI063) as a component in developing a targeted nanoparticle preparation which delivered an CaMKII inhibitor peptide to prevent heart-cell death during reperfusion. This research holds promise for the development of a medicine which can be used to prevent tissue damage during a heart-attack potentially aiding in life-saving therapy. Read more here: Wongrakpanich, Amaraporn, Angie S. Morris, Sean M. Geary, A. Joiner Mei-ling, and Aliasger K. Salem. "Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury." International Journal of Pharmaceutics (2017). http://www.sciencedirect.com/science/article/pii/S0378517317300704

“Abstract: An excess of calcium (Ca2+) influx into mitochondria during mitochondrial re-energization is one of the causes of myocardial cell death during ischemic/reperfusion injury. This overload of Ca2+ triggers the mitochondrial permeability transition pore (mPTP) opening which leads to programmed cell death. During the ischemic/reperfusion stage, the activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) enzyme is responsible for Ca2+ influx. To reduce CaMKII-related cell death, sub-micron particles composed of poly(lactic-co-glycolic acid) (PLGA), loaded with a CaMKII inhibitor peptide were fabricated. The CaMKII inhibitor peptide-loaded (CIP) particles were coated with a mitochondria targeting moiety, triphenylphosphonium cation (TPP), which allowed the particles to accumulate and release the peptide inside mitochondria to inhibit CaMKII activity. The fluorescently labeled TPP-CIP were taken up by mitochondria and successfully reduced ROS caused by Isoprenaline (ISO) in a differentiated rat cardiomyocyte-like cell line. When cells were treated with TPP-CIP prior ISO exposure, they maintained mitochondrial membrane potential. The TPP-CIP protected cells from ISO-induced ROS production and decreased mitochondrial membrane potential. Thus, TPP-CIP have the potential to be used in protection against ischemia/reperfusion injury.”

PLGA from PolySciTech used as part of optimized doxorubicin nanoparticle study

Tuesday, January 31, 2017, 2:56 PM ET

Nanoparticles references formulations which are submicron in size. A great deal of expertise goes into making nanoparticles with precise properties and this is an exciting field of research for a wide variety of treatments. Recently, researchers utilized PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) for formulation optimization of doxorubicin loaded particles. This research holds promised for improved chemotherapy strategies. Read more: Shaikh, Muhammad Vaseem, Manika Kala, and Manish Nivsarkar. "Formulation and optimization of doxorubicin loaded polymeric nanoparticles using Box-Behnken design: ex-vivo stability and in-vitro activity." European Journal of Pharmaceutical Sciences (2017). http://www.sciencedirect.com/science/article/pii/S0928098717300507

“Abstract: Biodegradable nanoparticles (NPs) have gained tremendous interest for targeting chemotherapeutic drugs to the tumor environment. Inspite of several advances sufficient encapsulation along with the controlled release and desired size range have remained as considerable challenges. Hence, the present study examines the formulation optimization of doxorubicin loaded PLGA NPs (DOX-PLGA-NPs), prepared by single emulsion method for cancer targeting. Critical process parameters (CPP) were selected by initial screening. Later, Box-Behnken design (BBD) was used for analyzing the effect of the selected CPP on critical quality attributes (CQA) and to generate a design space. The optimized formulation was stabilized by lyophilization and was used for in-vitro drug release and in-vitro activity on A549 cell line. Moreover, colloidal stability of the NPs in the biological milieu was assessed. Amount of PLGA and PVA, oil:water ratio and sonication time were the selected independent factors for BBD. The statistical data showed that a quadratic model was fitted to the data obtained. Additionally, the lack of fit values for the models was not significant. The delivery system showed sustained release behavior over a period of 120 h and was governed by Fickian diffusion. The multipoint analysis at 24, 48 and 72 h showed gradual reduction in IC50 value of DOX-PLGA-NPs (p < 0.05, Fig. 9). DOX-PLGA-NPs were found to be stable in the biological fluids indicating their in-vivo applicability. In conclusion, optimization of the DOX-PLGA-NPs by BBD yielded in a promising drug carrier for doxorubicin that could provide a novel treatment modality for cancer.”

Oral chemotherapeutic delivery system developed using PCL from PolySciTech

Monday, January 30, 2017, 5:16 PM ET

Paclitaxel is a widely applicable anticancer agent which prevents cancer cells from dividing and proliferating. Currently, the only administration route for paclitaxel is by intravenous injection. For chronic applications, this can be a very invasive procedure, such as surgical placement of a PICC line in the vein of the arm or port-a-cath directly into the entrance of the heart. Clearly, an oral delivery system would be preferred in terms of patience comfort as well as management of costs and potential complications associated with catheters. By itself, Paclitaxel has very poor uptake when administered orally. However, researchers have utilized PCL (PolyVivo AP129) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) and conjugated it to chitosan to form a biocompatible micelle system which significantly enhances paclitaxel absorption. This research holds promise for less-invasive and more sustainable delivery of paclitaxel to patients. Read more: Almeida, Andreia, Daniella Silva, Virginia Gonçalves, and Bruno Sarmento. "Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery." Drug Delivery and Translational Research (2017): 1-11. http://link.springer.com/article/10.1007/s13346-017-0357-8

“Abstract: In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents. Keywords: Chitosan, Polycaprolactone, Paclitaxel, Micelles, Drug delivery”

Stem-cell tissue scaffold for spinal-repair constructed using polymers from PolySciTech

Tuesday, January 24, 2017, 3:53 PM ET

An exciting application of biodegradable polymer technology is the regeneration of new tissue using an appropriate scaffold seeded with mesenchymal stem cells. Recently, researchers utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP045) as part of a scaffold system to support the regrowth of spinal cord tissue using stem cells. This research holds promise for potentially repairing spinal breaks as a treatment for paralysis. Read more: Ropper, Alexander E., Devang K. Thakor, InBo Han, Dou Yu, Xiang Zeng, Jamie E. Anderson, Zaid Aljuboori et al. "Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation." Proceedings of the National Academy of Sciences (2017): 201616340. http://www.pnas.org/content/early/2017/01/12/1616340114.short

“Abstract: Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9–T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI. Keywords: spinal cord injury recovery, neurobiology, mesenchymal stromal stem cell, PLGA, locomotion.”.

mPEG-PLLA from PolySciTech used for synthesis of photodynamic chemotherapy agent.

Friday, January 20, 2017, 2:08 PM ET

Photodynamic therapy is a novel cancer treatment option which utilizes special agents, referred to as photosensitizers. These reagents are inactive and non-toxic under typical conditions but can be activated by certain wavelengths of light to kill cancerous cells. The benefit of such a therapy, over conventional chemotherapy, is that the location of action can be controlled by selectively illuminating the tumor region. PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide variety of block copolymers which work well for forming micelle or nanoparticle formulations for medicinal delivery. Recently, mPEG-PLLA (PolyVivo AK004) was utilized by researchers at Wroclaw University as a precursor to synthesize zinc(II) phthalocyanine conjugate for photodynamic therapy. This research holds promise for safe and effective cancer therapy with lower side-effects. Read more: Lamch, Łukasz, Marta Tsirigotis-Maniecka, Julita Kulbacka, and Kazimiera A. Wilka. "Synthesis of new zinc (II) phthalocyanine conjugates with block copolymers for cancer therapy." Organic Chemistry part ii (2017): 433-445. http://www.arkat-usa.org/get-file/58826/

“Abstract: Synthetic routes towards new conjugates of hydrophilic zinc(II) phthalocyanine (ZnPc) with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic P123) and poly(L-lactide) (PLLA), are described. The main semiproduct ZnPc was obtained by heating 4-nitrophthalimide with urea and zinc chloride, followed by the reduction step. Steglich esterification was used to synthesize two ZnPc-conjugated block copolymers, further utilized in fabrication of polymeric micelles (PMs) - functionalized with the zinc(II) phthalocyanine-type moiety. Biological evaluation of the PMs indicated an acceptable biocompatibility level in accord with requirements in the field of nanotheranostics and nanomedicine. Keywords: ZnPc-conjugated block copolymers; cyclotetramerization; Steglich esterification; fluorescent polymeric micelles; diagnostic marker; in vitro biological evaluation”

Uses for Akanocure Stereotetrad Lactones 5b: Full Lactone Reductions

Friday, January 20, 2017, 2:06 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of (+)-neopeltolide fragments, a chemotherapeutic agent. This research holds promise for improved availability of chemotherapeutic agents. Read more: Mineeva, I. "New approach to the synthesis of macrocyclic core of cytotoxic lactone (+)-neopeltolide. Synthesis of CC segment basing on cyclopropanol intermediates." Russian Journal of Organic Chemistry 51, no. 8 (2015). http://link.springer.com/article/10.1134/S1070428015080023

“A new retrosynthetic procedure was developed for the synthesis of the macrocyclic core of a cytotoxic lactone (+)-neopeltolide utilizing cyclopropanol intermediates. The synthesis was suggested and carried out of the C7–C16 segment of (+)-neopeltolide to obtain (4S,6S)-6-[(2S)-2-hydroxypentyl]-4-methyltetrahydro-2H-pyran-2-one. The possibility was demonstrated of a formal synthesis based on the obtained product of the potential antitumor pharmaceutical (+)-neopeltolide.”

Uses for Akanocure Stereotetrad Lactones 5a: Full Lactone Reductions

Friday, January 20, 2017, 2:06 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of salinomycin, a powerful antibiotic agent which has proven itself effective against problematic bacterial such as MRSA. This research holds promise for improved antibiotics production. Read more: Yadav, J. S., Vinay K. Singh, and P. Srihari. "Formation of Substituted Tetrahydropyrans through Oxetane Ring Opening: Application to the Synthesis of C1–C17 Fragment of Salinomycin." Organic letters 16, no. 3 (2014): 836-839. http://pubs.acs.org/doi/abs/10.1021/ol403604u?journalCode=orlef7&quickLinkVolume=16&quickLinkPage=836&selectedTab=citation&volume=16

“The stereoselective synthesis of C1–C17 fragment of salinomycin is achieved. The strategy employs a desymmetrization approach and utilizes an intramolecular oxetane opening reaction with O-nucleophile to result in the tetrahydropyran skeleton as the key step.”

Uses for Akanocure Stereotetrad Lactones 4: lactone openings with sulfur nucleophiles

Friday, January 20, 2017, 2:05 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential reaction is the ring-opening of the lactone using sulfur (thiol) nucleophiles. Recently, this reaction has been applied to the synthesis of peloruside A, a potent chemotherapeutic agent. This research holds promise for improved availability of advanced chemotherapeutic agents. Read more: Raghavan, Sadagopan, and V. Vinoth Kumar. "A stereoselective synthesis of the C9–C19 subunit of (+)-peloruside A." Organic & biomolecular chemistry 11, no. 17 (2013): 2847-2858. http://pubs.rsc.org/en/content/articlelanding/2013/ob/c3ob27508f#!divAbstract

“Abstract: The stereoselective synthesis of a C9–C19 fragment of the potent antitumor agent peloruside A is disclosed. The C11 stereogenic centre was created by a vinylogous Mukaiyama aldol reaction following Carreira's protocol, with excellent stereocontrol. The C13 stereogenic centre was introduced by a substrate controlled reduction. The C15 stereocentre was fashioned using Noyori's asymmetric transfer hydrogenation while the Z-trisubstituted double bond was formed by a regioselective hydrostannation of an alkyne followed by methylation of the resultant vinyl stannane using Lipshutz's protocol. The C18 chiral centre was introduced by a chemoenzymatic route.”

Uses for Akanocure Stereotetrad Lactones 3: lactone openings with secondary nitrogen nucleophiles

Friday, January 20, 2017, 2:04 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. These lactones can be ring-opened using secondary nitrogens as the nucleophilic agent. Previously, this reaction has been used to synthesize portions of Aplyronine A, a potent, chemotherapeutic marine macrolide. This research holds promise for enhanced synthesis of difficult-to-source chemotherapy agents. Read more: Hong, Wan Pyo, Mohammad N. Noshi, Ahmad El-Awa, and Philip L. Fuchs. "Synthesis of the C1–C20 and C15–C27 Segments of Aplyronine A." Organic letters 13, no. 24 (2011): 6342-6345. http://pubs.acs.org/doi/abs/10.1021/ol2024746

“Abstract: The synthesis of C1–C20 and C15–C27 segments of Aplyronine A is described. Oxidative cleavage of cyclic vinyl sulfones has been used to prepare key fragments of Aplyronine A. Key precursors are united by Horner–Wadsworth–Emmons and Julia–Kociensky olefination for the respective elaboration of the C1–C20 and C15–C27 segments.”

Uses for Akanocure Stereotetrad Lactones 2b: lactone openings with primary nitrogen nucleophiles

Friday, January 20, 2017, 2:03 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One usage is opening the lactone ring utilizing primary nitrogens (amines). This method has been utilized to generate rhizopodin, a myxobacterial metabolite which is a potent actin-binding chemotherapeutic agent. This research holds promise for improved availability of effective chemotherapy agents. Read more: Dieckmann, Michael, Manuel Kretschmer, Pengfei Li, Sven Rudolph, Daniel Herkommer, and Dirk Menche. "Total synthesis of rhizopodin." Angewandte Chemie International Edition 51, no. 23 (2012): 5667-5670. http://onlinelibrary.wiley.com/doi/10.1002/anie.201301978/full

“The total synthesis of the myxobacterial metabolite rhizopodin, a potent actin-binding anticancer agent, has been achieved. The modular synthesis utilizes a common C1–C22 monomeric unit to assemble the dimeric 38-membered macrodiolide core, which was elaborated by a bidirectional boron-mediated aldol reaction to install the characteristic side-chains. The final global deprotection was critically dependent on the correct choice of silyl protecting groups at C16/C16′.”

Uses for Akanocure Stereotetrad Lactones 2a: lactone openings with primary nitrogen nucleophiles

Friday, January 20, 2017, 2:00 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One usage is opening the lactone ring utilizing primary nitrogens (amines). For example, these can be utilized to generate aldonamides, a class of widely applicable precursors in and of themselves. You can read more about this application here: Metta-Magaña, Alejandro J., Reyna Reyes-Martínez, and Hugo Tlahuext. "Crystal structure and NMR spectroscopy of aldonamides derived from d-glycero-d-gulo-heptono-1, 4-lactone." Carbohydrate research 342, no. 2 (2007): 243-253. http://www.sciencedirect.com/science/article/pii/S0008621506005325

“Abstract: We report the preparation of 12 aldonamides derived from d-glycero-d-gulo-heptono-1,4-lactone, their NMR characterization and study (13C, 1H, 15N NMR) in Me2SO-d6 solution. The evaluation of the coupling constants 3JH,H has shown that the sugar chain conformation in solution is all-trans for the studied amides. Because some amides crystallized, we discussed the crystal packing and found motifs. The conformation of the amides in the crystal structures displays two sickles at C2 and C3, with the exception of one that is all-trans. The bends cause the formation of the mean planes C1–C2–C3 and C3–C4–C5–C6–C7 with an average interplanar angle of 88°. We found three main kinds of crystal packing depending on the N-substituent; head-to-tail, bilayer and pseudo-hexagonal mode, all the three show hydrogen-bonding networks that stabilize the crystal lattice. Keywords: Aldonamides; Conformation; 15N NMR; Crystal packing; Hydrogen bonding”

Uses for Akanocure Stereotetrad Lactones 1b: lactone openings with oxygen nucleophiles

Friday, January 20, 2017, 1:59 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One of the uses is to open the lactone ring utilizing an oxygen nucleophile. This reaction has been successfully applied towards the generation of (+)-Neopeltolide, a promising cytostatic, anti-proliferative macrolide which has a broad range of activity against cancerous cells. The chemical was originally isolated from a deep-water sponges and is very difficult to source naturally in usable quantities. This research usage holds promise for commercial scale synthesis of chemotherapeutic reagents that are difficult to extract from natural resources. You can read more about this application here: Guinchard, Xavier, and Emmanuel Roulland. "Total synthesis of the antiproliferative macrolide (+)-neopeltolide." Organic letters 11, no. 20 (2009): 4700-4703. http://pubs.acs.org/doi/abs/10.1021/ol902047z?journalCode=orlef7&quickLinkVolume=11&quickLinkPage=4700&selectedTab=citation&volume=11

“A concise total synthesis of the very promising antiproliferative macrolide (+)-neopeltolide (1) has been performed in 16 steps. The main steps of this approach are a RuII-catalyzed alkyne−enal coupling, a Pd0-catalyzed desulfurative cross-coupling, and a stereoselective InIII-catalyzed propargylation. Four stereogenic centers out of six have been set thanks to substrate-controlled diastereoselective reactions with minimal reliance on protecting groups.”

Uses for Akanocure Stereotetrad Lactones 1a: lactone openings with oxygen nucleophiles

Friday, January 20, 2017, 1:59 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One of the uses is to open the lactone ring utilizing an oxygen nucleophile. This synthetic route has previously been used to generate peloruside A, a non-taxoid-site microtubule-stabilizing agent which has promise for chemotherapeutic actions similar to that of paclitaxel. This research usage holds promise for commercial scale synthesis of chemotherapeutic reagents that are difficult to extract from natural resources. You can read more about this application here: Hoye, Thomas R., Junha Jeon, Lucas C. Kopel, Troy D. Ryba, Manomi A. Tennakoon, and Yini Wang. "Total Synthesis of Peloruside A through Kinetic Lactonization and Relay Ring‐Closing Metathesis Cyclization Reactions." Angewandte Chemie International Edition 49, no. 35 (2010): 6151-6155. http://onlinelibrary.wiley.com/doi/10.1002/anie.201002293/full

“Abstract: A convergent total synthesis of peloruside A (1) is described. The key strategic features are a diastereoselective lactonization to generate a C5–C9 valerolactone from the C2-symmetric ketone 3, and a relay ring-closing metathesis reaction to produce a dehydrovalerolactone 2. A new isomer of 1, the valerolactone isopeloruside A (iso-1), was identified. MOM=methoxymethyl.”

Stereotetrad lactone precursors from Akanocure Pharmaceuticals now available through Akina, Inc.

Tuesday, January 17, 2017, 10:03 AM ET

The PolySciTech division of Akina, Inc. (www.polyscitech.com) strives to provide unique and hard-to-find research reagents. Thanks to a distribution arrangement with Akanocure Pharmacueticals, a Purdue University spin-off company which focuses on finding synthetic routes for hard-to-obtain nature-based pharmaceutical ingredients, we are now distributing stereospecific precursors for generation of polypriopionate medicines. You can see more details about these exciting materials here (https://akinainc.com/polyscitech/products/akanocure/index.php). These chemicals represent an exciting class of novel therapeutic compounds within the polyketide family. You can learn more about this class of materials and their therapeutic potential in a recent review article: Koskinen, Ari MP, and Kaisa Karisalmi. "Polyketide stereotetrads in natural products." Chemical Society Reviews 34, no. 8 (2005): 677-690. https://www.researchgate.net/profile/Ari_Koskinen/publication/7577323_Polyketide_Stereotetrads_in_Natural_Products/links/09e4150252cfc302d8000000.pdf

“Abstract: Natural products (or secondary metabolites) remain as the most important source for discovery of new and potential drug molecules. With high resolution data of their structures, and the advancement of synthesis possibilities, analysis of the natural products based on their specific structural features is valuable to those entering the field. In this tutorial review we attempt such an analysis indicating the salient features of the structural classes with examples of the synthesis of each one of them. As the particular class of natural products, we have chosen polyketides.”

Reactive precursor PLGA-PEG-COOH from PolySciTech used in development of theranostic colon-cancer therapy

Thursday, January 5, 2017, 7:08 PM ET

Cancer remains one of the most difficult diseases to treat partially due to difficulty in developing systems which can differentiate between cancerous tissue and normal tissue. Recently, researchers at Mashhad University and Tabriz University used PLGA-PEG-COOH (PolyVivo# AI076) as part of generating a targeted nanoparticle system. The particles were loaded both with doxorubicin, to provide for therapeutic treatment, and with iron oxide to act as a contrast agent for imaging. This research holds promise for both improved therapy and diagnosis for cancer. Read more: Mosafer, Jafar, Khalil Abnous, Mohsen Tafaghodi, Ahad Mokhtarzadeh, and Mohammad Ramezani. "In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy." European Journal of Pharmaceutics and Biopharmaceutics 113 (2017): 60-74. http://www.sciencedirect.com/science/article/pii/S0939641116309651

“Abstract: A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130 nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers.”

Triple-negative, metastatic breast-cancer targeted therapy developed using block polymers from PolySciTech

Thursday, January 5, 2017, 7:07 PM ET

Although many forms of breast-cancer respond well to conventional therapies, aggressive triple-negative breast cancer remains difficult to treat. Recently researchers at University of Minnesota developed novel antibodies capable of targeting metastatic cells. The researchers used Maleimide-PEG-PLGA (PolyVivo# AI119) to allow for antibody conjugation to nanoparticles and PLGA-rhodamine conjugate (PolyVivo# AV011), both from PolySciTech (www.polyscitech.com), to assist in nanoparticle tracking by fluorescence. This research holds promise to provide improved therapy for this lethal disease. Read more: Khanna, Vidhi Devendra. "Antibody Conjugated Nanoparticles for Targeting Metastatic Triple Negative Breast Cancer." PhD diss., UNIVERSITY OF MINNESOTA, 2016. http://conservancy.umn.edu/handle/11299/183298

“Abstract: Early detection and the availability of new treatments have improved the survival rates of patients presenting with local or regional breast cancer to as high as 99% and 85%, respectively. On the contrary, patients with metastatic disease have a dismal 5-year survival rate of 17%.1 Thus, there is an urgent need for treatment strategies directed towards metastasis. Our lab has developed antibodies (Clone 6 and AM6) capable of recognizing tumor cells that have undergone epithelial-to-mesenchymal transition (EMT), a key step in the generation of circulating tumor cells and metastasis. The goal of the current study was to determine whether we use these antibodies as targeting ligands for directing anticancer drug-loaded polymeric nanoparticles to metastatic triple negative breast cancer cells as a novel therapeutic option. Polymeric PLGA nanoparticles loaded with paclitaxel, a chemotherapeutic agent, were functionalized with the antibodies using thiol-maleimide chemistry. We optimized the conjugation reaction in order to achieve maximal cell uptake of nanoparticles without compromising antibody binding. In vitro studies were carried out in an MDA-MB-231 derivative cell line with enhanced lung metastatic potential as well as a melanoma metastatic cell line M12. Clone 6 nanoparticles and AM6 nanoparticles showed significant improvement in cellular uptake as well as retention. A competition experiment confirmed target-mediated uptake of nanoparticles. Cytotoxicity studies showed improved cell kill using Clone 6 nanoparticles and AM6 nanoparticles. Based on these promising in vitro results, we are currently carrying out in vivo studies in mice. The development of a targeted drug delivery system for the treatment of metastatic triple negative breast cancer can significantly enhance the survival rate for patients who often times have a life-expectancy of less than one year. Keywords: Antibody, Breast Cancer, Nanoparticles, Thiol-Maleimide”

Biosensor array system developed using precursors from PolySciTech

Thursday, January 5, 2017, 7:04 PM ET

One exciting field of research is the development of biosensors which allow for rapid, high-throughput tests of a wide array of analytes from a biological fluid. Recently, researchers utilized Folate-PEG-COOH (PolyVivo AE003) from PolySciTech (www.polyscitech.com) as part of development of a sensor array system. This research holds promise for improved diagnostic technologies. Read more: Beyene, Abraham G., Gozde S. Demirer, and Markita P. Landry. "Nanoparticle‐Templated Molecular Recognition Platforms for Detection of Biological Analytes." Current protocols in chemical biology (2016): 197-223. http://onlinelibrary.wiley.com/doi/10.1002/cpch.10/full

“Abstract: Molecular recognition of biological analytes with optical nanosensors provides both spatial and temporal biochemical information. A recently developed sensing platform exploits near-infrared fluorescent single-wall carbon nanotubes combined with electrostatically pinned heteropolymers to yield a synthetic molecular recognition technique that is maximally transparent through biological matter. This molecular recognition technique is known as corona phase molecular recognition (CoPhMoRe). In CoPhMoRe, the specificity of a folded polymer toward an analyte does not arise from a pre-existing polymer-analyte chemical affinity. Rather, specificity is conferred through conformational changes undergone by a polymer that is pinned to the surface of a nanoparticle in the presence of an analyte and the subsequent modifications in fluorescence readout of the nanoparticles. The protocols in this article describe a novel single-molecule microscopy tool (near-infrared fluorescence and total internal reflection fluorescence [nIRF TIRF] hybrid microscope) to visualize the CoPhMoRe recognition process, enabling a better understanding of synthetic molecular recognition. We describe this requisite microscope for simultaneous single-molecule visualization of optical molecular recognition and signal transduction. We elaborate on the general procedures for synthesizing and identifying single-walled carbon nanotube-based sensors that employ CoPhMoRe via two biologically relevant examples of single-molecule recognition for the hormone estradiol and the neurotransmitter dopamine. Keywords: fluorescence microscopy;molecular recognition;near-infrared imaging;nanoparticles;neurotransmitter;nIRF TIRF hybrid microscope;single-walled carbon nanotube (SWCNT);screening;single molecule imaging;sensors”

Nanoparticle based Parkinson’s disease treatment developed using block PEG-PLGA and maleimide reactive intermediates from PolySciTech

Thursday, January 5, 2017, 7:03 PM ET

Parkinson’s disease is both fatal and the second most common neurodegenerative disease in the world. One of the difficulties with treating it is formulating medicines so that they can cross from the blood-stream over into the brain tissue. Recently, researchers utilized block mPEG-PLGA (PolyVivo #AK104) and maleimide-PEG-PLGA (PolyVivo # AI109) from PolySciTech (www.polyscitech.com) to create a nanoparticle loaded with rotigotine, a dopamine agonist effective for Parkinson’s therapy. They used the maleimide groups to conjugate lactoferrin on the outside which assisted with uptake across the blood brain barrier. This system showed promise for non-toxic uptake into the brain when administered via intranasal route in mouse model. This research holds promise to provide for improved therapies for Parkinson’s disease. Read more: Bi, Chenchen, Aiping Wang, Yongchao Chu, Sha Liu, Hongjie Mu, Wanhui Liu, Zimei Wu, Kaoxiang Sun, and Youxin Li. "Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment." International Journal of Nanomedicine 11 (2016): 6547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153272/

“Abstract: Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. Keywords: rotigotine, lactoferrin-modified PEG-PLGA nanoparticles, brain targeting, intranasal delivery, Parkinson’s disease”

PLCL from PolySciTech used as part of 3D bio-printing a live-cell laden urethra for tissue engineering application

Tuesday, December 13, 2016, 2:21 PM ET

Tissue engineering, the field or repairing damaged or missing bodily tissue, often utilizes cell-scaffolds to provide an appropriate environment for cellular growth and proliferation. Often these scaffolds are manufactured using conventional solvent casting, electrospinning or other polymer processing techniques. With recent advances in 3D printing techniques, this methodology has come to the forefront for manufacturing of tissue engineering scaffolds. Recently, researchers utilized PLCL from PolySciTech (www.polyscitech.com) (PolyVivo AP179) and used it along with an advanced 3D printing system at the Wake Forest Institute for Regenerative Medicine (WFIRM) to create a mechanically biomimetic and cell-laden urethra which showed success in a rabbit model. This research holds promise to provide for advanced 3D printed or bioprinted parts for tissue engineering applications. Read more: Zhang, Kaile, Qiang Fu, James Yoo, Xiangxian Chen, Prafulla Chandra, Xiumei Mo, Lujie Song, Anthony Atala, and Weixin Zhao. "3D bioprinting of urethra with PCL/PLCL blend and dual autologous cells in fibrin hydrogel: an in vitro evaluation of biomimetic mechanical property and cell growth environment." Acta Biomaterialia (2016). http://www.sciencedirect.com/science/article/pii/S1742706116306778

“Abstract: Urethral stricture is a common condition seen after urethral injury. The currently available treatments are inadequate and there is a scarcity of substitute materials used for treatment of urethral stricture. The traditional tissue engineering of urethra involves scaffold design, fabrication and processing of multiple cell types. In this study, we have used 3D bio-printing technology to fabricate cell-laden urethra in vitro with different polymer types and structural characteristics. We hypothesized that use of PCL and PLCL polymers with a spiral scaffold design could mimic the structure and mechanical properties of natural urethra of rabbits, and cell-laden fibrin hydrogel could give a better microenvironment for cell growth. With using an integrated bioprinting system, tubular scaffold was formed with the biomaterials; meanwhile, urothelial cells (UCs) and smooth muscle cells (SMCs) were delivered evenly into inner and outer layers of the scaffold separately within the cell-laden hydrogel. The PCL/PLCL (50:50) spiral scaffold demonstrated mechanical properties equivalent to the native urethra in rabbit. Evaluation of the cell bioactivity in the bioprinted urethra revealed that UCs and SMCs maintained more than 80% viability even at 7 days after printing. Both cell types also showed active proliferation and maintained the specific biomarkers in the cell-laden hydrogel.These results provided a foundation for further studies in 3D bioprinting of urethral constructs that mimic the natural urethral tissue in mechanical properties and cell bioactivity, as well a possibility of using the bioprinted construct for in vivo study of urethral implantation in animal model. The 3D bioprinting is a new technique to replace traditional tissue engineering. The present study is the first demonstration that it is feasible to create a urethral construct. Two kinds of biomaterials were used and achieved mechanical properties equivalent to that of native rabbit urethra. Bladder epithelial cells and smooth muscle cells were loaded in hydrogel and maintained sufficient viability and proliferation in the hydrogel. The highly porous scaffold could mimic a natural urethral base-membrane, and facilitate contacts between the printed epithelial cells and smooth muscle cells on both sides of the scaffold. These results provided a strong foundation for future studies on 3D bioprinted urethra. Keywords: Urethra stricture; Urethra; Tissue engineering; 3D bioprinting; Regenerative medicine”

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

Tuesday, November 29, 2016, 1:55 PM ET

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”

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

Tuesday, November 22, 2016, 11:20 AM ET

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”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/.

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