Monthly Archives: November 2014

Low MW FITC tagged chitosan (KITO-3) from Akina, Inc. used for investigation of cuticle formation.

PolySciTech (www.polyscitech.com) provides a wide array of research polymers including chitosan derivatives. A recent PhD thesis by Patricia Ann Sprouse utilized KITO-3 (low molecular weight chitosan FITC tagged) in order to investigate interactions between carbohydrates and proteins within cuticles. Read more: Sprouse, Patricia Ann. “Evaluation of Structure-Property Relationships within Insect Cuticle to Identify Motifs for Biomaterial Design.” (2014). http://kuscholarworks.ku.edu/bitstream/handle/1808/15781/Sprouse_ku_0099D_13409_DATA_1.pdf?sequence=1&isAllowed=y

“ABSTRACT: Biological materials have mechanical properties that have been highly tuned for specific functions. The properties are governed by combinations of molecular interactions that are incorporated at multiple length scales in hierarchical structures. Establishing the links between molecular interactions and physical properties in biological materials has the potential to improve the design of structural biomaterials by offering effective design strategies. Insect cuticle, in particular, is an interesting model for studying structure-property relationships because it can have a wide range of mechanical properties despite a limited compositional makeup. The elytron, or outer wing cover, of the beetle is a strong and tough biomaterial made mostly of proteins, chitin, catechols and water. The objective of this thesis was to investigate molecular interactions among the components of elytral cuticle to both understand their role in governing in vivo properties as well as their future potential as biomaterial design motifs. The objective was addressed using two approaches. First, the intact elytron was studied to identify material design concepts that contribute to the strong and tough physical properties of the structure. Second, simplified systems of cuticular components were examined in vitro to help understand the in vivo roles of specific interactions with the future goal of providing new biomaterial design motifs. Studies on the intact elytron from the yellow mealworm beetle, Tenebrio molitor, determined that the cuticle is not compositionally uniform throughout development. Instead, new material is continuously secreted from the epidermal cells. The color change and the frequency dependence of the cuticle plateaued after 48 hours, indicating that the initially secreted material matures within 48 hours of eclosion. The mature cuticle bears the tensile load while additional material is subsequently deposited and matured over a week of development. Important contributions of both covalent and non-covalent interactions were identified in cuticle using dynamic mechanical analysis over a broad range of frequency, temperature and by treatments with non-covalent bond breaking-solvents. Indirect evidence pointed to the dominant role of covalent interactions in stabilizing the cuticle shortly after secretion from the epidermal cells. Dynamic mechanical analysis showed that the storage modulus of fully tanned and dried elytra was less frequency dependent (n = 0.013 ± 0.004) than the modulus of untanned and dried elytra (n = 0.05 ± 0.024), even at frequencies as low as 0.01 rad/s. Additionally, increasing the temperature from 25 to 150°C, up to the point of degradation, resulted in only a 3.5 fold decrease in the storage modulus and modest rise in the tan δ curve for fully tanned elytra. To further separate the role of covalent and non-covalent interactions in elytral cuticle, solvents were used to disrupt non-covalent interactions. More material could be extracted from partially tanned elytra than from fully tanned elytra, most likely reflecting the lower degree of covalent crosslinking in the immature layers of cuticle within partially tanned elytra. Soaking fully tanned elytra in formic acid, which disrupts hydrogen bonding, caused the static mechanical properties to resemble those of partially tanned elytra, which is consistent with the view that covalent crosslinks within the load bearing layers of cuticle are established within 48 hours. The role of non-covalent interactions was also highlighted by mechanical tests after treating with formic acid. The solvent caused a 5-fold decrease in the Young’s modulus of fully tanned elytra, suggesting that a significant portion of the stiffness (which increases 20-fold with maturation) is provided by non-covalent interactions. The added stiffness provided by non-covalent interactions appears to have been provided without compromising toughness; that is, apparent hydrogen bonding caused a proportional increase in fracture stress and decrease in fracture strain, thus leaving toughness unchanged. Despite uncovering important contributions from covalent and non-covalent interactions within the network as a whole, the complexity of the biological structure makes it difficult to identify the exact interactions contributing to the physical properties. Thus, simplified systems were used to study specific molecular interactions in vitro. The hypothesized interactions that were studied in vitro, namely protein-chitin complexation, protein-catechol and protein-protein crosslinks, and protein-Ni2+ complexation, were studied using two abundant cuticle proteins in the elytra of the red flour beetle, Tribolium castaneum, CPR27 and CP30. CPR27 has a conserved sequence of amino acids that has been hypothesized to bind chitin. Results from active microrheology showed that addition of CPR27 to fluorescently-labeled aqueous chitosan solutions caused a 2-fold decrease in viscosity. Since this microrheology technique allows for the simultaneous visualization of microstructure, the appearance of bright fluorescent spots was observed along with the drop in viscosity. Together the results indicated that CPR27 complexation with chitosan caused aggregation that effectively removed material from the vicinity of the microrheology probes. CP30, which does not contain the conserved chitin-binding sequence, did not display similar evidence of complexation. The role of quinone crosslinking of both proteins with the catechol, N-&beta-alanyldopamine, was examined using passive microrheology. Microparticle formation was observed in solutions containing protein and laccase, catechol and laccase, and protein, catechol and laccase. However, elasticity was observed only when the protein was present, consistent with the hypothesis that quinone crosslinking has a mechanical role in cuticle, as concluded by the studies on elytra. However, further tests are needed to reproduce the data and verify the origin of elasticity. The highly unusual sequence of highly repetitive short blocks of positive and negative residues in CP30 suggested that it may self-assemble or interact with multivalent metal ions. The protein was found to aggregate or adsorb to surfaces, preventing analysis, near the isoelectric point of 5.82. However, spectroscopic studies suggested the protein had an extended α-helical conformation at other pH conditions. CP30 was also shown to interact with nickel ions to form microparticles that induced elasticity in the fluid. The interactions involving these two cuticle proteins suggest new motifs that could be used in the design of tunable biomaterials. The rational design of proteins with specific covalent and non-covalent interactions with polysaccharides or ions, inspired by insect cuticle, may lead to biomaterials with enhanced mechanical properties.”

12 Days of Christmas Discount

Around West Lafayette, IN where PolySciTech (www.polyscitech.com) is based someone neglected to inform the weather that it is only time for fall not winter. In the spirit of this we are launching our “12 Days of Christmas Discount” early.  Starting with November 18 – January 9th, use the discount code “12DAYS” to get an additional 12% discount on the following items:  AK24 PLGA-PEG-PLGA LG 75:25 (Mn ~1,100:1,000:1,100 Da); AK25 mPEG-PLLA (Mw ~750:1,000 Da); AK28 PLCL-PEG-PLCL LA:CL 50:50  (Mw ~5,700:4,600:5,700 Da); AK31 mPEG-PDLLA (Mw ~5,000:35,000 Da); AO03 Poly(vinyl phosphonate) sodium salt (Viscosity = 50-250 cP; 1% in water at 60 RPM); AO04 Poly(sulfopropyl acrylate) (Viscosity = 10-100 cP; 1% in water at 60 RPM); AO18 Poly(vinylcaprolactone-co-methoxy poly(ethylene glycol) methacrylate) (95:5 VCL:mPEG); AP021 PLGA LG 85:15 acid endcap (Mn 35,000-45,000 Da) (L-lactide); AP024 PLGA LG 85:15 ester endcap  (Mn 35,000-45,000 Da); AP082 PLGA LG 50:50 acid endcap  (Mn 25,000-35,000 Da); AP040 PLGA LG 50:50 acid endcap  (Mn 15,000-25,000 Da) and AP052 PLGA LG 85:15 acid endcap  (Mn 200,000-300,000 Da) (L-lactide).

12 days of christmas discount

Polymers from Polyscitech used to develop ABT-737/camptothecin co-delivery system to treat colorectal cancer

Recent research using polymers from www.polyscitech.com (PolyVivo AK10) have found that encapsulation of chemotherapeutic agents ABT-737 and camptothecin reduces their side effects as well as induces higher cancer cell aptoposis. Read more:  Schmid, D., G. E. Jarvis, F. Fay, D. M. Small, M. K. Greene, J. Majkut, S. Spence et al. “Nanoencapsulation of ABT-737 and camptothecin enhances their clinical potential through synergistic antitumor effects and reduction of systemic toxicity.” Cell death & disease 5, no. 10 (2014): e1454. http://www.nature.com/cddis/journal/v5/n10/full/cddis2014413a.html

 

“Abstract: The simultaneous delivery of multiple cancer drugs in combination therapies to achieve optimal therapeutic effects in patients can be challenging. This study investigated whether co-encapsulation of the BH3-mimetic ABT-737 and the topoisomerase I inhibitor camptothecin (CPT) in PEGylated polymeric nanoparticles (NPs) was a viable strategy for overcoming their clinical limitations and to deliver both compounds at optimal ratios. We found that thrombocytopenia induced by exposure to ABT-737 was diminished through its encapsulation in NPs. Similarly, CPT-associated leukopenia and gastrointestinal toxicity were reduced compared with the administration of free CPT. In addition to the reduction of dose-limiting side effects, the co-encapsulation of both anticancer compounds in a single NP produced synergistic induction of apoptosis in both in vitro and in vivo colorectal cancer models. This strategy may widen the therapeutic window of these and other drugs and may enhance the clinical efficacy of synergistic drug combinations.”

PolySciTech Polymer used in magnetofluorescent nanocomposites preparation

Recently polymers from www.polyscitech.com (PolyVivo AK51 and PolyVivo AI75 for mPEG-PLGA and Mal-PEG-PLGA respectively) were used to stabilize MFNCs generated as well as conjugate the nanoparticles to thiolated neutravidin for binding assay. Read more: Demillo, Violeta G., Mingxia Liao, Xiaoshan Zhu, Doug Redelman, Nelson G. Publicover, and Kenneth W. Hunter. “Fabrication of MnFe< sub> 2</sub> O< sub> 4</sub>-CuInS< sub> 2</sub>/ZnS Magnetofluorescent Nanocomposites and Their Characterization.” Colloids and Surfaces A: Physicochemical and Engineering Aspects (2014). http://www.sciencedirect.com/science/article/pii/S0927775714007870

“Abstract: Magnetofluorescent nanocomposites (MFNCs) providing a single nanoscale platform with multimodal properties are gaining momentum in biological manipulation, biomedical imaging and therapies. In this work, we report the preparation of MFNCs integrating MnFe2O4 magnetic nanoparticles (MNPs), CuInS2/ZnS quantum dots (QDs) and poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) in a tetrahydrofuran (THF)/water solvent system. Through sonication and quick solvent displacement, multiple nanoparticles of each type are co-encapsulated within the hydrophobic core of PEG-PLGA micelles. The developed fabrication process is simple and fast. Moreover, due to the low toxicity of CuInS2/ZnS QDs, the fabrication process is environmentally benign. The fabricated MFNCs were further characterized regarding their fundamental physical, chemical and biological properties. Results reveal that the MFNCs possess high (Mn + Fe) recovery rates, and the optical properties and magnetic relaxivity of the MFNCs are sensitive to the MNP:QD mass ratios in the fabrication. Furthermore, the MFNCs present excellent stability in aqueous solutions, minimal cytotoxicity, and capability for bioconjugation. This study opens an avenue for the MFNCs to be employed in broad biological or biomedical applications. Keywords: Magnetofluorescent nanocomposites; MnFe2O4 magnetic nanoparticles; CuInS2/ZnS quantum dots; Poly(ethylene glycol)-b-poly(lactide-co-glycolide); Optical properties; Magnetic relaxivity; Colloidal stability; Cytotoxicity; Bioconjugation”

PolySciTech polymer used in pancreatic cancer delivery

Recently polymer purchased from PolySciTech (www.polyscitech.com) (Polyvivo AK09 mPEG-P(DL)La) was utilized to generate a nanoparticle system for delivery of docetaxel to pancreatic cancer. Read more: Gupta, R., D. Cvetkovic, C. M. Ma, and L. Chen. “Targeted Approach for Prostate Cancer Treatment: Synthesis and Characterization of Docetaxel-Loaded Perfluorocarbon Nanodroplets.” J Cancer Sci Clin Oncol 1, no. 1 (2014): 102. http://www.annexpublishers.com/articles/JCSCO/volume-1-Issue-1/Targeted-Approach-for-Prostate-Cancer-Treatment-Synthesis-and-Characterization-of-Docetaxel-Loaded-Perfluorocarbon-Nanodroplets.pdf

“Abstract: The purpose of this study is to synthesize and characterize nanodroplets, loaded with docetaxel for treatment of prostate cancer under MR-guided focused ultrasound. Water insoluble docetaxel encapsulated in nanodroplets is expected to be delivered into tumors with greater efficiency while minimizing drug related systemic toxicities when used in combination with focused ultrasound. The sequence of our studies toward development and characterization of docetaxel-loaded nanodroplets is as follows. First, we developed methods for synthesis of ultrasound-responsive, docetaxel-loaded nanodroplets (Doc-nd) by a solid dispersion technique. Secondly, we characterized Doc-nd by its morphology and size distributions using a dynamic light scattering (DLS) method. To check the consistency of the data obtained from DLS, size distribution was also studied using an independent technique by analyzing bright field microscopy images of Doc-nd in software ImageJ. Thirdly, we studied the encapsulation efficiency and the release kinetics of docetaxel from Doc-nd in phosphate buffer saline. Finally, we performed in vitro cytotoxicity studies using a human prostate cancer cell line (LNCaP). Our data showed that peak sizes of spherical Doc-nd were 222±15 nm. These sizes favor passive accumulation into most tumors thus potentially increasing localized docetaxel concentration. A high encapsulation efficiency of 93.70% was obtained for Doc-nD. The release kinetics studies showed that docetaxel was released from Doc-nd in a three- staged release pattern with an initial release of 30% in one hour followed by a 50% release until 12h and an 85% release after three days. In vitro cytotoxicity studies using LNCaP cells indicated a time-dependent cytotoxic profile and verified encapsulation of docetaxel in the nanodroplets. Our study  suggested that Doc-nd may have the potential for treating prostate cancer with an improved therapeutic ratio when combined with  MR-guided focused ultrasound.  Keywords: Docetaxel; Perfluorocarbon Nanodroplets; Ultrasound; Prostate Cancer”

PolySciTech Clerk Position available

Description

Responsible for performing daily office tasks such as filing, recording, maintaining records, copying, posting, and other similar duties, using a computer terminal. Follows organization and department procedures to complete tasks in a timely manner. Requires a high school diploma or its equivalent with 0-3 years of experience in the field or in a related area. Has knowledge of commonly-used concepts, practices, and procedures within a particular field.

We are looking for the following qualifications and experience. Previous office experience, Filing, faxing, scanning, copying, binding, Sales & retail experience, Customer Service experience, QuickBooks or other bookkeeping software experience, Experience invoicing, quoting and open invoice follow-up, Experience with UPS, FedEx and USPS shipping online, Dependable, Reliable and experienced with confidentiality, Very organized and with attention to detail, Willingness to learn new things and work as a team player, Good communication and patience, Good telephone procedures with customers and vendors, Doesn’t mind any tasks as assigned, Experienced with deadlines for completing tasks or shipments

This position is flexible 8:00 a.m.-1:00 p.m. or preferably 9:00 a.m.-2:00 p.m. Monday-Friday; approximately 25-30 hours a week. It pays $11.00/hr. Applicant will not be sponsored for US work visa.

Company Description Akina, Inc. is a small research based company located in West Lafayette, IN. Akina has a variety of in-house research projects related to the pharmaceutical and biomedical field as well as commercializes research products directly via the PolySciTech division. See more by browsing www.polyscitech.com

Application Instructions: Email Resumes to jg@akinainc.com.

PEG-PLA used for cervical cancer gene therapy

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA as well as other polymers. Recently gene loaded nanoparticles were utilized as part of a delivery system to control the delivery of DNA to cervical cancer cells. Read more Liu, Bo, Shu-Mei Han, Xiao-Yong Tang, Li Han, and Chang-Zhong Li. “Cervical Cancer Gene Therapy by Gene Loaded PEG-PLA Nanomedicine.” Asian Pacific Journal of Cancer Prevention 15, no. 12 (2014): 4915-4918. Full-Text available: http://www.apocpcontrol.org/paper_file/issue_abs/Volume15_No12/4915-4918%204.6%20Bo%20Liu.pdf

“Abstract: Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Folate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/ DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer. Keywords: Gene therapy – cervical cancer – folate coating – targeted nanomedicine”

PolySciTech PLGA used as part of development of bioadhesive/bone implants

PolySciTech (www.polyscitech.com) provides a wide array of PLGA and related biodegradable polyesters. Recently PLGA from PolySciTech was utilized as a control in development of citrate based bioadhesive. Read more: Xie, Denghui, Jinshan Guo, Reza Mehdizadeh, Richard T. Tran, Dawei Sun, Guoying Qian, Dadi Jin, Xiaochun Bai, and Jian Yang. “Development of Injectable Citrate-Based Bioadhesive Bone Implants.” Journal of Materials Chemistry B (2014). http://pubs.rsc.org/en/content/articlehtml/2014/tb/c4tb01498g

“Abstract: Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2-4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF.”