Tuesday, February 7, 2017

Akanocure Press Release

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

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.”

Tuesday, January 31, 2017

PLGA from PolySciTech used as part of optimized doxorubicin nanoparticle study

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.”

Monday, January 30, 2017

Oral chemotherapeutic delivery system developed using PCL from PolySciTech

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”

Tuesday, January 24, 2017

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

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.”.


Friday, January 20, 2017

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

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

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.”