Monthly Archives: April 2014

PEG-PLA aids in dentin tissue disinfection

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers. Recently these types of polymers have been used to research into improved drug delivery into dentin tissue as a means of disinfection.  Read more: Lau, Michael, Ridwan Haseeb, Francisco Montagner, and Danieli Rodrigues. “Encapsulation of biological stains for drug delivery imaging and microscopy in dentin tubules (733.6).” The FASEB Journal 28, no. 1 Supplement (2014): 733-6. http://www.fasebj.org/content/28/1_Supplement/733.6.short

“ABSTRACT: Introduction: Bacteria are able to remain into dentin after the root canal disinfection. Drug penetration into the tubules can be a key component for infection control. This study uses the synthesis of poly(ethylene glycol)-block-poly(L-lactide) PEG/PLA encapsulated biological stain particles to characterize the penetration depth of drug delivery systems with Confocal Laser Scanning Microscopy (CLSM). Methodology: Encapsulation of the biological stain was done with an oil-water emulsion-evaporation technique. The PEG/PLA copolymer and the stain were dissolved in the oil phase while the surfactant was dissolved in water. The oil phase and water phase was combined and emulsified then stirred. The particles were centrifuged, washed, and lyophilized. Characterizing the particle size and fluorescence was done with CLSM (VK-X200 Keyence Laser Scanning Microscope). Results: The microscopy has shown particle formation in the 0.3-1.0 m range, which depended on the method of emulsification: homogenizing or sonication. CLSM revealed that the particles fluoresce under light with 525-605 nm wavelengths. Conclusion: The encapsulation technique effectively encapsulated the biological stain to penetrate the dentin tubules. With particle size similar to dentin morphology, the encapsulated stain proliferation into the dentin tubules will model dentin penetration of drug delivery systems of similar size.”

mPEG-PLA delivered tacrolimus reduces transplant rejection

PolySciTech (www.polyscitech.com) provides a wide array of mPEG-PLA polymers for research in drug delivery applications. Recently these types of polymer was utilized to aid the delivery of tacrolumus in a rat liver transplant model and was found to improve survival time. Read more: Xu, Wei, Peixue Ling, and Tianmin Zhang. “Toward immunosuppressive effects on liver transplantation in rat model: Tacrolimus loaded poly (ethylene glycol)-poly (d, l-lactide) nanoparticle with longer survival time.” International journal of pharmaceutics 460.1 (2014): 173-180. http://www.sciencedirect.com/science/article/pii/S0378517313009307

 

“Abstract: In this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Drug loading (DL) and encapsulation efficiency (EE) can be changed by varying the mass ratio of FK506/MPEG-PLA. Furthermore, transmission electron microscope (TEM) and Malvern Zetasizer were used to investigate the properties of FK506/MPEG-PLA nanoparticles (DL = 9.5%), which were monodisperse (PDI = 0.100 ± 0.023) with a mean particle size of 90.5 ± 1.5 nm. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. We further preliminarily evaluated immunosuppressive effect on liver transplantation in rat model. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule.

Graphical abstract. In this study, tacrolimus (FK506) was encapsulated into a biodegradable poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) block copolymer using a double emulsion-solvent evaporation technique. Compared with FK506 capsule, in vitro release profile showed that FK506/MPEG-PLA nanoparticles exhibited sustained release. Meanwhile, the higher concentration and longer retention time in plasma were also confirmed in vivo. The survival time of the rat administrated FK506/MPEG-PLA nanoparticles was obviously prolonged than that of the control group administrated FK506 capsule. Keywords: Tacrolimus; MPEG-PLA; Nanoparticle; Immunosuppressive; Liver transplantation”Xu, 2014

PEG-PLGA block copolymer for treatment of ovarian cancer

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA block copolymers and Maleimide-PEG-PLGA reactive polymers for research applications. Recently these types of polymers were utilized to generate APRPG (Ala-Pro-Arg-Pro-Gly) labelled micelles for delivery of angiogenesis inhibitor TNP-470 to ovarian cancer cells. Read more: Wang, Yunfei, Peifeng Liu, Yourong Duan, Xia Yin, Qi Wang, Xiaofei Liu, Xinran Wang et al. “Specific cell targeting with APRPG conjugated PEG–PLGA nanoparticles for treating ovarian cancer.” Biomaterials 35, no. 3 (2014): 983-992. http://www.sciencedirect.com/science/article/pii/S0142961213011629

“Abstract: Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)–poly (lactic acid) (PEG–PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG–PLA and mPEG–PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (−14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic. Keywords: Nanoparticles; TNP-470; Antiangiogenesis; Ovarian cancer; Antitumor efficiency”

mPEG-PLGA for MRI contrast agent delivery/cancer theranostic approach

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA block copolymers. Recently these types of polymers have been co-formulated with albumin-gadolinium to generate theranostic nanoparticles for cancer treatment. Read more: Liu, Qiuming, Hongshi Zhu, Jingya Qin, Haiqing Dong, and Jianzhong Du. “Theranostic Vesicles Based on Bovine Serum Albumin and Poly (ethyleneglycol)-block-Poly (L-lactic-co-glycolic acid) for Magnetic Resonance Imaging and Anticancer Drug Delivery.” Biomacromolecules (2014). http://pubs.acs.org/doi/abs/10.1021/bm500438x

“Presented in this article is the preparation of a new theranostic vesicle which exhibits excellent in vitro and in vivo T1 magnetic resonance (MR) imaging contrast effect and good anticancer drug delivery ability. The theranostic vesicle has been easily prepared based on an amphiphilic biocompatible and biodegradable dibock copolymer, poly(ethylene glycol)-block-poly(l-lactic-co-glycolic acid) (PEG-b-PLGA) and bovine serum albumin-gadolinium (BSA-Gd) complexes. Dynamic light scattering (DLS), transmission electron microscopy (TEM), UV–vis spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements confirmed the formation and physiological stability of BSA-Gd@PEG-b-PLGA vesicles. Furthermore, the in vitro and in vivo MR imaging experiments revealed their excellent T1-weighted MR imaging function. Red blood cell hemolysis and cytotoxicity experiments confirmed their good blood compatibility and low cytotoxicity. Doxorubicin (DOX) loading and release experiments indicated a more retarded release rate of DOX in those theranostic vesicles than sole PEG-b-PLGA nanoparticles without BSA. Overall, this new biocompatible and biodegradable vesicle shows promising potential in theranostic applications.”

Liu, 2014

PEG-PLA for controlled antibiotic release

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers. Recently these types of polymers were utilized to delivery antibiotics during root canal treatment. Read more here: Haseeb, Ridwan, Michael Lau, Lucas Rodriguez, Franciso Montagner, Kelli Palmer, Mihaela Stefan, and Danieli Rodrigues. “Encapsulation of antibiotics in poly (ethylene glycol)-block-poly (L-lactide) for delivery in dentin tubules during root canal treatment (733.4).” The FASEB Journal 28, no. 1 Supplement (2014): 733-4. http://www.fasebj.org/content/28/1_Supplement/733.4.short

“Abstract: Aim: To encapsulate an antibiotic in oral applications with PEG/PLA-block copolymer into microparticles for infected dentin tubules. To maintain drug release for extended periods to prevent bacterial regrowth after root canal treatment. Methodology: Drug encapsulation was carried out through an oil-water emulsion-solvent evaporation method. In summary, the PEG/PLA copolymer and the oral drug were dissolved in an oil phase (dichloromethane), which was combined with an aqueous (polyvinyl alcohol and de-ionized water). The solution was stirred, centrifuged, washed, and lyophilized. Particle size was determined using digital microscopy. Antimicrobial effectiveness was assessed in vitro by placing small amounts of encapsulated particles on bacterial agar plate cultures and monitoring growth inhibition. Results: Encapsulated particles ranged in size from 300 nm to 1.0 m. A 2 week bacterial inhibition test showed that the particles exhibited zones of inhibition between 3 mm and 5 mm. Conclusion: The proposed method with the PEG/PLA copolymer encapsulates the oral antibiotic producing particles with size distribution that may penetrate the dentinal tubules (2.5 m in diameter). Bacterial inhibition tests showed that the particles inhibited bacterial growth after 2 weeks. Ongoing bacterial inhibition tests will determine the release profile of the microparticles.”

Colorectal cancer treatment via mPEG-PLA micelles

PolySciTech (www.polyscitech.com) provides a wide array of mPEG-PLA as well as active endcap PEG-PLA block copolymers with –COOH, -NHS, -Maleimide and other active endcaps. Recently these types of polymers were applied to treatment of colorectal cancer cells in-vivo using the F56 targeting peptide and delivering vincristine. Read more: Wang, Chao, Mei Zhao, Ya-Rong Liu, Xin Luan, Ying-Yun Guan, Qin Lu, De-Hong Yu, Fan Bai, Hong-Zhuan Chen, and Chao Fang. “Suppression of colorectal cancer subcutaneous xenograft and experimental lung metastasis using nanoparticle-mediated drug delivery to tumor neovasculature.” Biomaterials 35, no. 4 (2014): 1215-1226. http://dx.doi.org/10.1016/j.biomaterials.2013.08.091

 

“Abstract: Antiangiogenic therapy is a validated approach for colorectal cancer (CRC) treatment. However, diverse adverse effects inevitably appear due to the off-target effect of the approved antiangiogenic inhibitors on the physiological functions and homeostasis. This study was to investigate a new tumor vessel targeting nanoparticulate drug delivery system, F56 peptide conjugated nanoparticles loading vincristine (F56-VCR-NP), for the effective treatment of CRC subcutaneous xenograft and experimental lung metastasis model. The controlled release behavior and in vivo pharmacokinetic profile of F56-VCR-NP were characterized. The tumor vessel targeting and antiangiogenic activity of F56-VCR-NP was evaluated in human umbilical vein endothelial cells (HUVEC, a classical cell model mimicking tumor vascular EC), subcutaneous human HCT-15 xenograft in immunodeficient nude mice, and experimental CT-26 lung metastasis model in immunocompetent mice. The therapeutic efficacy (animal survival and toxicity) was further investigated in the model of CT-26 lung metastasis in mice. F56-VCR-NP could achieve 30-day controlled drug release in PBS (pH 7.4) and exhibited favorable long-circulating feature in vivo. F56-VCR-NP could accurately target the CRC neovasculature and elicit nanoparticle internalization in the tumor vascular EC, where the antiangiogenic VCR-induced dramatic EC apoptosis and necrosis of CRC tissue. F56-VCR-NP significantly prolonged the mouse survival with no obvious toxicity (weight loss and anepithymia) in the CT-26 lung metastasis mice model, and this pronounced antitumor effect was closely related with the decreased microvessel density in the metastases. The present nanoparticle-based targeted antiangiogenic therapy may provide a new promising approach for the therapy of CRC and lung metastasis, which deserves further translational research. Keywords: Tumor neovasculature; Nanoparticles; Antiangiogenic therapy; Colorectal cancer; Lung metastasis”

Publication utilizes PolyVivo AK09 as delivery system for photoactivated prodrug

Recent publication from University of Oklahoma utilized Polyvivo AK09 (mPEG-PLA)(www.polyscitech.com) as a delivery system for their custom synthesized prodrug Pc-(L-CA4)2 which activates upon exposure to red light.  This system successfully ablated tumors in a mouse model. Read more:  Bio, Moses, Pallavi Rajaputra, Gregory Nkepang, and Youngjae You. “A Far-Red Light Activatable, Multi-Functional Prodrug for Fluorescence Optical Imaging and Combinational Treatment.” Journal of medicinal chemistry(2014).  http://pubs.acs.org/doi/abs/10.1021/jm5000722

“ABSTRACT: We recently developed “photo-unclick chemistry”, a novel chemical tool involving the cleavage of aminoacrylate by singlet oxygen, and demonstrated its application to visible light-activatable prodrugs. In this study, we prepared an advanced multifunctional prodrug, Pc-(L-CA4)2, composed of the fluorescent photosensitizer phthalocyanine (Pc), an SO-labile aminoacrylate linker (L), and a cytotoxic drug combretastatin A-4 (CA4). Pc-(L-CA4)2 had reduced dark toxicity compared with CA4. However, once illuminated, it showed improved toxicity similar to CA4 and displayed bystander effects in vitro. We monitored the time-dependent distribution of Pc-(L-CA4)2 using optical imaging with live mice. We also effectively ablated tumors by the illumination with far-red light to the mice, presumably through the combined effects of photodynamic therapy (PDT) and released chemotherapy drug, without any sign of acute systemic toxicity.”

Bio, 2014

New Product: mPEG-b-poly(5-benzyloxytrimethylene carbonate)

PolySciTech (www.polyscitech.com) is proud to present a new product. mPEG-b-poly(5-benzyloxytrimethylene carbonate) copolymer is now available (PolyVivo AK78).  Similar copolymers have previously been used for a wide array of micelle based drug delivery applications and this polymer has been shown to be biodegradable and non-cytotoxic. Read more: Zeng, Faquan, Jubo Liu, and Christine Allen. “Synthesis and Characterization of Biodegradable Poly (ethylene glycol)-b lock-poly (5-benzyloxy-trimethylene carbonate) Copolymers for Drug Delivery.” Biomacromolecules 5, no. 5 (2004): 1810-1817. http://pubs.acs.org/doi/abs/10.1021/bm049836a

“Abstract: Amphiphilic diblock copolymers with various block compositions were synthesized with monomethoxy-terminated poly(ethylene glycol) (MePEG) as the hydrophilic block and poly(5-benzyloxy-trimethylene carbonate) (PBTMC) as the hydrophobic block. When the copolymerization was conducted using MePEG as a macroinitiator and stannous 2-ethylhexanoate (Sn(Oct)2) as a catalyst, the molecular weight of the second block was uncontrollable, and the method only afforded a mixture of homopolymer and copolymer with a broad molecular weight distribution. By contrast, the use of the triethylaluminum-MePEG initiator yielded block copolymers with controllable molecular weight and a more narrow molecular weight distribution than the copolymers obtained using Sn(Oct)2. GPC and 1H NMR studies confirmed that the macroinitiator was consumed and the copolymer composition was as predicted. Two of the newly synthesized MePEG-b-PBTMC copolymers were evaluated in terms of properties primarily relating to their use in micellar drug delivery. MePEG-b-PBTMC micelles with a narrow monomodal size distribution were prepared using a high-pressure extrusion technique. The MePEG-b-PBTMC copolymers were also confirmed to be biodegradable and noncytotoxic.”

mPEG-5BZTMC-advert

PLGA nanoparticles that promote immune response against cancer

PolySciTech (www.polyscitech.com) provides a variety of PLGA type polymers. Recently these kinds of polymers were utilized to generate a nanoparticle delivery system to deliver a combination of siRNA for immumosuppressive gene and tumor antigens to enhance immune response against tumor cells for chemotherapeutic applications.  Read more: Heo, Min Beom, Mi Young Cho, and Yong Taik Lim. “Polymer nanoparticles for enhanced immune response: Combination delivery of tumor antigen and siRNA for immunosuppressive gene to dendritic cells.” Acta biomaterialia (2014). http://dx.doi.org/10.1016/j.actbio.2013.12.050

“Abstract: In this study, we report on polymer nanoparticles (NPs) that can induce an enhanced immune response in dendritic cell (DC)-based cancer immunotherapy by the combined delivery of tumor antigen and small interference RNA (siRNA) for the immunosuppressive gene to DCs. DCs are specialized antigen-presenting cells (APCs) that capture, process and present antigens and induce an antigen-specific cytotoxic T lymphocyte response. Because the suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of the APC-based immune response, the inhibition of SOCS1 gene expression is essential for DCs to enhance antigen-specific anti-tumor immunity. Multifunctional poly(lactide-co-glycolic acid) (PLGA) NPs that can deliver tumor antigen and siRNA for immunosuppressive SOCS1 genes to DCs simultaneously were fabricated by the emulsion solvent evaporation method. We have found that the encapsulation efficiency of small-sized and hydrophilic SOCS1 siRNA into hydrophobic PLGA matrix is drastically enhanced by the help of a tumor model antigen such as ovalbumin (OVA), and the encapsulation efficiency of siRNA in PLGA (SOCS1 siRNA only) NPs and PLGA (OVA/SOCS1 siRNA) NPs was2% and 57.6%, respectively. PLGA (OVA/SOCS1 siRNA) NPs were efficiently taken up by bone-marrow-derived dendritic cells (BMDCs) and showed no detectable toxic effect. The knockdown of SOCS1 in BMDCs by PLGA (OVA/SOCS1 siRNA) NPs enhanced pro-inflammatory cytokine (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-12 and IL-2) expression. Additionally, PLGA (OVA/SOCS1 siRNA) NP-treated BMDCs could elicit an immune response through cross-presentation in OVA-specific CD8 T cells that express IL-2 cytokine. Taken together, the combined delivery of NPs that can deliver both tumor antigen and immunosuppressive gene siRNA to BMDCs simultaneously could be a potent strategy to enhance immunotherapeutic effects in BMDC-based cancer therapy.”

Heo, 2014

Allyl Lactide (cat# AM08) now available

New Product, PolyScitech (www.polyscitech.com) is proud to provide allyl lactide monomer. This monomer is useful for the generation of side-chain modified PLA’s such as cationic polylactide created by thiol-ene click reaction. Read more: Chen, Chih‐Kuang, Wing‐Cheung Law, Ravikumar Aalinkeel, Bindukumar Nair, Atcha Kopwitthaya, Supriya D. Mahajan, Jessica L. Reynolds et al. “Well‐Defined Degradable Cationic Polylactide as Nanocarrier for the Delivery of siRNA to Silence Angiogenesis in Prostate Cancer.” Advanced healthcare materials 1, no. 6 (2012): 751-761.  http://onlinelibrary.wiley.com/doi/10.1002/adhm.201200094/full

“Abstract: Well-defined tertiary amine-functionalized cationic polylactides (CPLAs) are synthesized by thiol-ene click functionalization of an allyl-functionalized polylactide, and utilized for the delivery of interleukin-8 (IL-8) siRNA via CPLA-IL-8 siRNA nanoplexes. The CPLAs possess remarkable hydrolytic degradability, and their cytotoxicity is relatively low. The CPLA-IL-8 siRNA nanoplexes can be readily taken up by prostate cancer cells, resulting in significant IL-8 gene silencing. It is found that the degradability and cytotoxicity of CPLAs, as well as the transfection efficiency of the CPLA-IL-8 siRNA nanoplexes, positively correlate with the amine mol% of CPLAs. Keywords: cationic polymer;degradable polymer;prostate cancer;gene delivery;RNAi”

Allyl Lactide monomer