mPEG-PCL used for targeted dexamethasone delivery to inflamed joints as part of arthritis treatment research.

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including mPEG-PCL. Arthritis is a highly prevalent immune disorder which leads to joint destruction. It can be treated with anti-inflammatory agents, such as dexamethasone (a steroidal anti-inflammatory), but systemic application of this drug can lead to side-effects. Injecting the drug locally into joints is problematic as more than one joint may be affected by arthritis. Recently, mPEG-PCL was utilized to generate dexamethasone micelles and injected into an arthritic rat model intravenously. As part of inflammatory process, the vasculature around inflamed tissue becomes very ‘leaky’ and allows for easy passage of nanoparticles into inflamed tissue. This process allowed for preferential uptake of the mPEG-PCL nanoparticles into the inflamed arthritic tissue where the dexamethasone served to reduce inflammation and tissue damage. This targeted delivery allows for treatment of multiple joints from one injection and prevents side effects. This research holds promise for improved arthritis treatment. Read more: Wang, Qin, Jiayu Jiang, Wenfei Chen, Hao Jiang, Zhirong Zhang, and Xun Sun. “Targeted delivery of low-dose dexamethasone using PCL–PEG micelles for effective treatment of rheumatoid arthritis.” Journal of Controlled Release 230 (2016): 64-72. http://www.sciencedirect.com/science/article/pii/S0168365916301821

“Abstract: Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block–poly (ε­caprolactone) (PCL–PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8 mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL–PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL–PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders. Keywords: rheumatoid arthritis; PCL–PEG; Dexamethasone; Side effect”

Thermogel applications of PolySciTech products

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide variety of biodegradable polymers some of which exhibit reverse thermal gelation. This process occurs for polymers that have a mixture of hydrophilic and hydrophobic regions. In cold conditions, the water molecules preferentially affiliate with the hydrophilic portions of the polymer and the material dissolves into micelles. At higher temperatures, the water molecules transition to a free state and the polymer micelles form bridges between each other to form a gel held together by weak hydrophobic interactions (e.g. London dispersion forces).  There are many practical applications for these materials. Here’s a few, recently published applications of note:

Prostate cancer treatment/vaccine adjuvant: Auburn University researchers utilized PolyVivo AK097 (PLGA-PEG-PLGA) as a delivery agent for vaccines against the sex hormone GnRH. Such a system holds promise for both fertility control as well as prostate cancer treatment. (http://www.sciencedirect.com/science/article/pii/S0168165615301498)

Gel-Printing: Collaborators at Purdue University and KITECH utilized PolyVivo AO023 (PNIPAM-co-AM) as a gel printing system in which an inkjet-printer was modified so as to print the cold polymer solution onto a warmed surface. This system holds promise for controlled printing of living cells or tissues. (http://www.sciencedirect.com/science/article/pii/S0017931015310565)

Wound disinfection: Researchers at the University of Toronto utilized PolyVivo AO031 (PNVCL) as a carrier of gold nanorods into an infected wound model. By applying a carefully defined laser to the system, they were able to rapidly raise the temperature of the wound surface without increasing temperature underneath allowing for extremely precise, localized heating. This system kills bacteria regardless of antibiotic resistance. This system holds promise for treatment of MRSA or other localized infections where conventional antibiotics are ineffective. (http://www.sciencedirect.com/science/article/pii/S0142961216301144)

These are just a few examples. For all PST research products, you can see research articles and other literature regarding their usage at our site here https://akinainc.com/polyscitech/products/polyvivo/referenced_by.php

PolySciTech Poly(caprolactone) used as part of development of a theranostic nanoparticle system as a potential treatment for cancer

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers. Recently, PCL from PolySciTech (PolyVivo catalog AP113) was used as part of development of an NIR sensitive nanoparticle system for delivery of paclitaxel. This research holds promise for improved therapeutic strategies. Read more: Su, Jinghan, Huiping Sun, Qingshuo Meng, Qi Yin, Pengcheng Zhang, Zhiwen Zhang, Haijun Yu, and Yaping Li. “Bioinspired Nanoparticles with NIR‐Controlled Drug Release for Synergetic Chemophotothermal Therapy of Metastatic Breast Cancer.” Advanced Functional Materials (2016). http://onlinelibrary.wiley.com/doi/10.1002/adfm.201603381/full

“Abstract: Optimal nanosized drug delivery systems (NDDS) require long blood circulation and controlled drug release at target lesions for efficient anticancer therapy. Red blood cell (RBC) membrane-camouflaged nanoparticles (NPs) can integrate flexibility of synergetic materials and highly functionality of RBC membrane, endowed with many unique advantages for drug delivery. Here, new near-infrared (NIR)-responsive RBC membrane-mimetic NPs with NIR-activated cellular uptake and controlled drug release for treating metastatic breast cancer are reported. An NIR dye is inserted in RBC membrane shells, and the thermoresponsive lipid is employed to the paclitaxel (PTX)-loaded polymeric cores to fabricate the RBC-inspired NPs. The fluorescence of dye in the NPs can be used for in vivo tumor imaging with an elongated circulating halftime that is 12.3-folder higher than that of the free dye. Under the NIR laser stimuli, the tumor cellular uptake of NPs is significantly enhanced to 2.1-fold higher than that without irradiation. The structure of the RBC-mimetic NPs can be destroyed by the light-induced hyperthermia, triggered rapid PTX release (45% in 30 min). These RBC-mimetic NPs provide a synergetic chemophotothermal therapy, completely inhibited the growth of the primary tumor, and suppress over 98% of lung metastasis in vivo, suggesting it to be an ideal NDDS to fight against metastatic breast cancer.”

PolySciTech PLGA used as part of research investigating drug-eluting electrospun mesh systems

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers. Recently, researchers at University of Washington used PolySciTech PLGA (PolyVivo Cat# AP154) as part of an electrospun system for delivery of model drug tenofovir (a hydrophilic antiretroviral medication). They investigated this system both in terms of drug release as well as the relationship between drug release and polymer degradation and mechanical performance. This research holds promise for improved drug-eluting polymer meshes which could be used for a wide array of applications. Read more: Chou, Shih-Feng, and Kim A. Woodrow. “Relationships between mechanical properties and drug release from electrospun fibers of PCL and PLGA blends.” Journal of the Mechanical Behavior of Biomedical Materials (2016). http://www.sciencedirect.com/science/article/pii/S1751616116303101

“Highlights Drug-polymer interactions in electrospun drug-eluting fibers. Correlations of drug release, polymer degradation on fiber tensile properties. Drug partitioning in blend polyester fibers. Abstract: Electrospun nanofibers have the potential to achieve high drug loading and the ability to sustain drug release. Mechanical properties of the drug-incorporated fibers suggest the importance of drug-polymer interactions. In this study, we investigated the mechanical properties of electrospun polycaprolactone (PCL) and poly (D,L-lactic-co-glycolic) acid (PLGA) fibers at various blend ratios in the presence and absence of a small molecule hydrophilic drug, tenofovir (TFV). Young’s modulus of the blend fibers showed dependence of PLGA content and the addition of the drug. At PCL/PLGA (20/80) composition, Young’s modulus and tensile strength were independent of drug loading up to 40 wt% due to offsetting effect from drug-polymer interactions. In vitro drug release studies suggested that release of TFV significantly decreased fiber mechanical properties. In addition, mechanically stretched fibers displayed a faster release rate as compared to the non-stretched fibers. Finally, drug partition in the blend fibers was estimated using a mechanical model and then experimentally confirmed by using a composite of individually stacked fiber meshes. This work provides scientific understanding on the dependence of drug release and drug loading on the mechanical properties of drug-eluting fibers. Keywords: Electrospun fibers; Mechanical properties; Drug loading; Drug release; Drug-polymer interaction; Drug partition”

PLGA-NH2 from PolySciTech investigated for improved cellular uptake as chemotherapy delivery system

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable copolymers including Amine endcapped PLGA. Recently, researchers at Kangwon National University in Korea utilized PLGA-NH2 (PolyVivo AI062) and unreactive PLGA (PolyVivo AP063) from PolySciTech to develop a nanoparticle system for the delivery of phloretin (a natural dihydrochalcone which induces cancer apoptosis, doi: 10.1002/ijc.24189) to test Hep-2 cells (human laryngeal carcinoma). This research holds promise for improved chemotherapeutic strategies. Read more: Lee, Song Yi, and Hyun-Jong Cho. “Amine-functionalized poly (lactic-co-glycolic acid) nanoparticles for improved cellular uptake and tumor penetration.” Colloids and Surfaces B: Biointerfaces (2016). http://www.sciencedirect.com/science/article/pii/S0927776516306270

“Abstract: Amine-functionalized poly(lactic-co-glycolic acid) (PLGA-NH2) nanoparticles (NPs) were developed for the delivery of phloretin. PLGA-NH2/phloretin NPs with 237 nm mean diameter, narrow size distribution, and around −6 mV zeta potential were fabricated by a modified emulsification-solvent evaporation method. The results of solid state studies revealed that drug was successfully incorporated into the polymeric NPs. The initial particle size of developed NPs was maintained after 24 h incubation in human serum albumin (HSA) solution, fetal bovine serum (FBS), and phosphate buffered saline (PBS). Sustained and higher drug release patterns at acidic pH (pH 5.5), compared with neutral pH (pH 7.4), from PLGA-NH2 NPs were observed. The experimental data of flow cytometry and confocal laser scanning microscopy (CLSM) studies suggested that PLGA-NH2 NPs may have an improved cellular accumulation efficiency, compared with PLGA NPs, in Hep-2 cells (human laryngeal carcinoma). Also, PLGA-NH2 NPs exhibited enhanced growth inhibitory effects rather than PLGA NPs in Hep-2 spheroid model. By introducing a simple strategy based on amine-functionalization of PLGA NPs (without installing complicated functional moieties), improved cellular uptake and antitumor efficacies without severe toxicity, compared with unmodified PLGA NPs, have been accomplished. Highlights: Poly(lactic-co-glycolic acid)-amine (PLGA-NH2) nanoparticles (NPs) were fabricated. Phloretin was encapsulated into the PLGA-NH2 NPs for tumor-targeted delivery. PLGA-NH2 NPs exhibited an improved cellular accumulation, compared with PLGA NPs. Enhanced tumor penetration efficiency in spheroids was observed in PLGA-NH2 NPs group.”

Have Some Fun With PolySciTech Invaders:

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers and other research products. Despite the seriousness of our work, we do have a sense of fun. As a fun way to say ‘Thank You’ to our customers, we’ve uploaded a playable PolySciTech Invaders game, which has prizes including product discount codes and t-shirts onto our website. Check out the game here http://polyscitech.com/invaders/.

PLGA-PEG-Mal from PolySciTech used for development of prostate cancer targeting nanoparticle as part of drug-delivery system

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including diblock PEG-PLGA and reactive Maleimide-PEG-PLGA. Recently, researchers at Albany utilized polymers from PolySciTech to develop anti-CD24 conjugated nanoparticles. CD24 is overexpressed in almost 70% of all human cancers (Nature Communications 6, Article number: 5909 doi:10.1038/ncomms6909) which makes it an attractive target for drug delivery. Docetaxel, an anti-mitotic chemotherapy agent, is well established for having good efficacy against cancer cells. By developing a system which targets docetaxel loaded nanoparticles to cancer, the researchers were able to shrink tumors in the mouse model relative to control. This research holds promise for improved chemotherapeutic strategies to treat cancer effectively while minimalizing side effects. Read more: Bharali, Dhruba J., Thangirala Sudha, Huadong Cui, Badar M. Mian, and Shaker A. Mousa. “Anti-CD24 Nano-targeted Delivery of Docetaxel for the Treatment of Prostate Cancer.” Nanomedicine: Nanotechnology, Biology and Medicine (2016). http://www.sciencedirect.com/science/article/pii/S1549963416301290

“Abstract: Nanoparticle (NP)-mediated, noninvasively targeted and image-guided therapies have potential to improve efficacy and safety of cancer therapeutics. We report synthesis and use of poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) NPs for targeted delivery of docetaxel. We synthesized docetaxel encapsulated NPs conjugated to anti-CD24 (for targeting) and/or an optical probe (for tracking) and evaluated efficacy in a prostate cancer mouse model. We observed preferential accumulation of anti-CD24 conjugated NPs (encapsulating docetaxel) compared to the non-conjugated NPs 24 hours after a single injection into luciferase-expressing PC3M prostate cancer tumor. In the same mouse model, we found significant (P < 0.01) accumulation of docetaxel (~10-fold higher) in tumor after treatment with PLGA-PEG NPs encapsulating docetaxel and conjugated to anti-CD24 compared to non-conjugated NPs. Enhanced accumulation was associated with reduced tumor mass and tumor viability. These data support the potential impact of nano-targeted delivery of chemotherapy in enhancing the differential tumor delivery and anticancer efficacy in prostate cancer. Graphical Abstract: Synthesis of PLGA-PEG nanoparticles encapsulating docetaxel and conjugated to anti-CD24. Abbreviations: Cy7, Cy7 N-hydroxysuccinimid; MAL, maleimide; PLGA-PEG, poly(lactide-co-glycolide)-polyethylene glycol; PVA, polyvinyl alcohol”

Co-development project with Hatch51 for commercially available 3DCellMaker bioprinting system

Akina, Inc. (www.polyscitech.com) has launched a joint project with additive engineering firm Hatch51 (http://hatch51.com/) for the creation of a 3D gel-printing system optimized for printing of Akina’s synthetic thermogelling 3DCellmaker. The printer will allow for low-temperature, gentle, printing of the thermogelling polymer solution so as to allow for printing of live-cell loaded solution to form 3D structures and tissues. Such a system has promise for a wide array of future applications. Those interested in the hardware portion of the system are encouraged to contact Hatch51 directly regarding this (contact@hatch51.com)

A recent review article details the possibilities of bio-printing and its applications. Read more here: Jakab, Karoly, Cyrille Norotte, Francoise Marga, Keith Murphy, Gordana Vunjak-Novakovic, and Gabor Forgacs. “Tissue engineering by self-assembly and bio-printing of living cells.” Biofabrication 2, no. 2 (2010): 022001. http://iopscience.iop.org/article/10.1088/1758-5082/2/2/022001/meta

“Abstract: Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion.”

PolyVivo biodegradable cross-linkable thermogel PLA-PEG-PLA diacrylate for reinforced 3D gel printing

Additive manufacturing, or 3D printing, has reimagined the way manufacturing is accomplished and brought in a new concept for prototype generation. Typical, polymer-melt printing, however is unsuitable for generation of tissue engineering products such as stem-cell seeded scaffolds or other bioactive materials. For this, 3D printing can be accomplished by printing a cold solution comprised of a thermosentive polymer dissolved in cell-growth media or other suitable aqueous solution onto a gently warmed platform (~37 °C). There are, however, drawbacks to this technique in that the thermogelation of polymers does not provide for high mechanical strength. To address this need, PolySciTech has launched PolyVivo AI145 (https://akinainc.com/polyscitech/products/polyvivo/?highlight=AI145#h). This is a thermogelling PLA-PEG-PLA with diacrylate endcaps that gels at 37 °C and allows for the gelled structures to be reinforced by photo-initiation of the acrylates to form a biodegradable crosslinked structure. Such a system could allow for 3D printing of cell-seeded thermogels with suitable mechanical requirements to allow for printing a structure with height and geometry not possible so far with conventional thermogelation 3D printing.

A similar type process was applied by researchers in Tornio, Italy for generating a sol-gel printed substrate. This research holds promise for the development of reinforced tissue scaffolds for cellular growth or tissue repair as well as other engineered materials. Read more: Chiappone, Annalisa, Erika Fantino, Ignazio Roppolo, Massimo Lorusso, Diego Manfredi, Paolo Fino, Candido Fabrizio Pirri, and Flaviana Calignano. “3D Printed PEG-Based Hybrid Nanocomposites Obtained by Sol–Gel Technique.” ACS applied materials & interfaces 8, no. 8 (2016): 5627-5633. http://pubs.acs.org/doi/abs/10.1021/acsami.5b12578

“In this work, three-dimensional (3D) structured hybrid materials were fabricated combining 3D printing technology with in situ generation of inorganic nanoparticles by sol–gel technique. Those materials, consisting of silica nanodomains covalently interconnected with organic polymers, were 3D printed in complex multilayered architectures, incorporating liquid silica precursors into a photocurable oligomer in the presence of suitable photoinitiators and exposing them to a digital light system. A post sol–gel treatment in acidic vapors allowed the in situ generation of the inorganic phase in a dedicated step. This method allows to build hybrid structures operating with a full liquid formulation without meeting the drawbacks of incorporating inorganic powders into 3D printable formulations. The influence of the generated silica nanoparticle on the printed objects was deeply investigated at macro- and nanoscale; the resulting light hybrid structures show improved mechanical properties and, thus, have a huge potential for applications in a variety of advanced technologies. Keywords: 3D printing; digital light processing (DLP); hybrid nanocomposite; mechanical properties; sol−gel”

Polydioxanone used for cellular alignment study to understand Muscle tissue regeneration

 

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers. Recently, poly(dioxanone) (PDO) was added to this list with pilot product PolyVivo AP186. This polymer has been used in research to elucidate the effect of alignment in cell signaling. This research is crucial to creating functional muscle regeneration scaffolds. Read more: McClure, Michael J., Nicholas M. Clark, Sharon L. Hyzy, Charles E. Chalfant, Rene Olivares-Navarrete, Barbara D. Boyan, and Zvi Schwartz. “Role of integrin α7β1 signaling in myoblast differentiation on aligned polydioxanone scaffolds.” Acta biomaterialia (2016). http://www.sciencedirect.com/science/article/pii/S1742706116302082

“Abstract: The aligned structural environment in skeletal muscle is believed to be a crucial component in functional muscle regeneration. Myotube formation is increased on aligned biomaterials, but we do not fully understand the mechanisms that direct this enhanced fusion. Previous studies indicate that the α7 integrin subunit is upregulated during myoblast differentiation, suggesting that signaling via α7β1 mediates the effect of alignment. To test this hypothesis, we took advantage of an in vitro model using random and aligned polydioxanone (PDO) matrices and C2C12 myoblasts. We measured expression and production of myoblast markers: paired box-7 (Pax7), myogenic differentiation factor-1 (MyoD), myogenin (MyoG), myogenic factor-6 (Myf6), and myosin heavy chain (MyHC). To examine the role of α7β1 signaling, we measured expression and production of α7, α5, and β1 and myoblast markers in wild type cells and in cells silenced for α7 and assessed effects of silencing on myogenic differentiation. Downstream signaling via ERK1/2 mitogen activated protein kinase (MAPK) was examined using a specific MEK1/2 inhibitor. Alignment increased mRNAs and protein for early (MyoD) and late (MyoG, MyHC) myoblast markers in comparison to non-aligned matrices, and these levels corresponded with increased α7 protein. α7-silencing reduced MyoG and MyHC protein in cells cultured on tissue culture polystyrene and aligned PDO matrices compared to wild type cells. Inhibition of ERK1/2 blocked effects of alignment. These data suggest that alignment regulates myogenic differentiation via α7β1 integrin signaling and ERK1/2 mediated gene expression. Statement of Significance: Muscle regeneration in severe muscle injuries is complex, requiring a sequence of events to promote healing and not fibrosis. Aligned biomaterials that recapitulate muscle environments hold potential to facilitate regeneration, but it is important to understand cell-substrate signaling to form functional muscle. A critical component of muscle signaling is integrin α7β1, where mice lacking α7 exhibit a dystrophic phenotype and impaired regeneration. Here, we report the role of α7β1 signaling in myoblast differentiation on aligned biomaterials. α7-silenced myoblasts were found to regulate myogenic differentiation and demonstrate defective fusion. Our data shows reduced levels of myogenin and myosin heavy chain protein, while MyoD remains unchanged. These results support the hypothesis that α7β1 signaling plays a role in substrate-dependent tissue engineering strategies. Keywords: Muscle; Polydioxanone fiber alignment; Surface topography; Biomimetic material; Myoblast differentiation”