Monthly Archives: July 2014

Folate decorated PEG-PLA for curcumin delivery to cancer cells

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA both methoxy endcapped and reactive derivatives.  Recently these types of polymers were used to generate a folate decorated nanoparticle delivery system for curcumin. Read more: Yang, Chunfen, Hao Chen, Jie Zhao, Xin Pang, Yanwei Xi, and Guangxi Zhai. “Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.” Colloids and Surfaces B: Biointerfaces (2014). http://www.sciencedirect.com/science/article/pii/S0927776514002318

“Highlights: The folate-modified Curcumin loaded micelles (Cur-FPPs) were prepared by thin-film hydration method. The Cur-FPPs increased the cytotoxicity and cellular uptake of Cur on MCF-7 and HepG2 cells in vitro. The Cur-FPPs prolonged the half-life of Cur in rats. Abstract: Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70 nm, the encapsulating efficiency and drug-loading were 80.73 ± 0.16% and 4.84 ± 0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur. Keywords: Curcumin; Folate; mPEG-PLA; Micelles”

Yang, 2014 PEG-PLA curcumin

PEG-PLA with specific targeting for Her2+ breast cancer for SiRNA delivery

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers and precursors for developing nanoparticle based drug delivery technologies.  Recently PEG-PLA polymers were used to generate a nanoparticle decorated with anti-Her2 antibody fragment and shown to successfully deliver SiRNA to the cancer cells inducing apoptosis.  Read more: Dou, Shuang, Xian‐Zhu Yang, Meng‐Hua Xiong, Chun‐Yang Sun, Yan‐Dan Yao, Yan‐Hua Zhu, and Jun Wang. “ScFv‐Decorated PEG‐PLA‐Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer.” Advanced healthcare materials (2014). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201400037/full

“Keywords:siRNA delivery;single-chain antibody fragment;Her2;tumor targeting;breast cancer Abstract: Patients with Her2-overexpressing (Her2+) breast cancers generally have a poorer prognosis due to the high aggressiveness and chemoresistance of the disease. Small interfering RNA (siRNA) targeting the gene encoding polo-like kinase 1 (Plk1; siPlk1) has emerged as an efficient therapeutic agent for Her2+ breast cancers. Poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PLA)-based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of siPlk1 to Her2+ breast cancer, anti-Her2 single-chain variable fragment antibody (ScFvHer2)-decorated PEG-PLA-based nanoparticles with si Plk1 encapsulation (ScFvHer2-NPsi Plk1) are developed. With the rationally designed conjugation site, ScFvHer2-NPsiRNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2+ breast cancer cells. Therefore, ScFvHer2-NPsi Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2+ breast cancer cells, when compared with nontargeted NPsi Plk1. More importantly, ScFvHer2-NPsiRNA markedly enhances the accumulation of siRNA in Her2+ breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose-dependent anti-tumor efficacy further demonstrates that ScFvHer2-decorated PEG-PLA-based nanoparticles with siPlk1 encapsulation can significantly enhance the inhibition of Her2+ breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFvHer2-decorated PEG-PLA-based nanoparticles show great potential for targeted RNA interference therapy of Her2+ breast tumor.”

PEG-PLA and cationic derivatives used as part of SiRNA therapy for triple negative breast cancer

PolySciTech (www.polyscitech.com) provides a variety of PEG-PLA block copolymers as well as cationic polymers such as cationic CPLA derivatives and PEI derivatives. Recently combinations of PEG-PLA block copolymers and cationic derivatives have been utilized for delivery of SiRNA inducing apoptosis in cancer cells. Read more: Liu, Yang, Yan-Hua Zhu, Cheng-Qiong Mao, Shuang Dou, Song Shen, Zi-Bin Tan, and Jun Wang. “Triple Negative Breast Cancer Therapy with CDK1 siRNA Delivered by Cationic Lipid Assisted PEG-PLA Nanoparticles.” Journal of Controlled Release (2014). http://www.sciencedirect.com/science/article/pii/S0168365914004702

“Abstract: There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NPsiCDK1) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NPsiCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer. Keywords: Triple-negative breast cancer; Synthetic lethality; siRNA delivery; Cationic lipid assisted nanoparticle; Cyclin-dependent kinase 1”

Liu, 2014 triple negative breast cancer

Use of PEG-PLGA for inhaled Alzheimer’s treatment

PolySciTech (www.polyscitech.com) provides a wide variety of PEG-PLGA and reactive conjugate precursors such as Mal-PEG-PLGA for drug delivery uses. Recently similar polymers have been utilized to generate inhalable nanoparticles conjugated to Solanum tuberosum lectin for deliver basic fibroblast growth factor to the brain as a potential treatment for Alzheimer’s disease. Read more:  Zhang, Chi, Jie Chen, Chengcheng Feng, Xiayan Shao, Qingfeng Liu, Qizhi Zhang, Zhiqing Pang, and Xinguo Jiang. “Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease.” International journal of pharmaceutics 461, no. 1 (2014): 192-202. http://www.sciencedirect.com/science/article/pii/S0378517313010430

“Abstract: Disabilities caused by neurodegeneration have become one of the main causes of mortality in elderly population, with drug distribution to the brain remaining one of the most difficult challenges in the treatment of the central nervous system (CNS) diseases due to the existence of blood–brain barrier. Lectins modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles could enhance the drug delivery to the brain following intranasal administration. In this study, basic fibroblast growth factor (bFGF) was entrapped in nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively binds to N-acetylglucosamine on the nasal epithelial membrane for its brain delivery. The resulting nanoparticles had uniform particle size and negative zeta potential. The brain distribution of the formulations following intranasal administration was assessed using radioisotopic tracing method. The areas under the concentration–time curve of 125I-bFGF in the olfactory bulb, cerebrum, and cerebellum of rats following nasal application of STL modified nanoparticles (STL-bFGF-NP) were 1.79–5.17 folds of that of rats with intravenous administration, and 0.61–2.21 and 0.19–1.07 folds higher compared with intranasal solution and unmodified nanoparticles, respectively. Neuroprotective effect was evaluated using Mirror water maze task in rats with intracerebroventricular injection of β-amyloid25–35 and ibotenic acid. The spatial learning and memory of Alzheimer’s disease (AD) rats in STL-bFGF-NP group were significantly improved compared with AD model group, and were also better than other preparations. The results were consistent with the value of choline acetyltransferase activity of rat hippocampus as well as the histological observations of rat hippocampal region. The histopathology assays also confirmed the in vivo safety of STL-bFGF-NP. These results clearly indicated that STL-NP was a promising drug delivery system for peptide and protein drugs such as bFGF to enter the CNS and play the therapeutic role. Keywords: Basic fibroblast growth factor (bFGF); Solanum tuberosum lectin (STL); Brain delivery; Nanoparticles; Intranasal administration; Alzheimer’s disease (AD)”

Mal-PEG-PLA/mPEG-PLA used for brain cancer therapy

PolySciTech (www.polyscitech.com) provides a wide array of maleimide-PEG-PLA and mPEG-PLA block copolymers for forming nanoparticles. Recently these types of polymers were used as precursors to generate paclitaxel loaded nanoparticles decorated with extra domain B aptamer for targeting towards glioma cells for brain cancer therapy. Read more: Gu, Guangzhi, Quanyin Hu, Xingye Feng, Xiaoling Gao, Jiang Menglin, Ting Kang, Di Jiang, Qingxiang Song, Hongzhuan Chen, and Jun Chen. “PEG-PLA nanoparticles modified with APT-EDB peptide for enhanced anti-angiogenic and anti-glioma therapy.” Biomaterials (2014). http://www.sciencedirect.com/science/article/pii/S014296121400698X

“Abstract: Tumor neovasculature and tumor cells dual-targeting chemotherapy can not only destroy the tumor neovasculature, cut off the supply of nutrition and starve the tumor cells, but also directly kill tumor cells, holding great potential in overcoming the drawbacks of anti-angiogenic therapy only and improving the anti-glioma efficacy. In the present study, by taking advantage of the specific expression of fibronectin extra domain B (EDB) on both glioma neovasculature endothelial cells and glioma cells, we constructed EDB-targeted peptide APTEDB-modified PEG-PLA nanoparticles (APT-NP) for paclitaxel (PTX) loading to enable tumor neovasculature and tumor cells dual-targeting chemotherapy. PTX-loaded APT-NP showed satisfactory encapsulated efficiency, loading capacity and size distribution. In human umbilical vein endothelial cells, APT-NP exhibited significantly elevated cellular accumulation via energy-dependent, caveolae and lipid raft-involved endocytosis, and improved PTX-induced apoptosis therein. Both in vitro tube formation assay and in vivo matrigel angiogenesis analysis confirmed that APT-NP significantly improved the antiangiogenic ability of PTX. In U87MG cells, APT-NP showed elevated cellular internalization and also enhanced the cytotoxicity of the loaded PTX. Following intravenous administration, as shown by both in vivo live animal imaging and tissue distribution analysis, APT-NP achieved a much higher and specific accumulation within the glioma. As a result, APT-NP-PTX exhibited improved anti-glioma efficacy over unmodified nanoparticles and Taxol® in both subcutaneous and intracranial U87MG xenograft models. These findings collectively indicated that APTEDB-modified nanoparticles might serve as a promising nanocarrier for tumor cells and neovasculature dual-targeting chemotherapy and hold great potential in improving the efficacy anti-glioma therapy. Keywords: Nanoparticles; APTEDB peptide; Dual-targeting; Paclitaxel; Glioma therapy”

mPEG-PLA loaded with gemcitabine and doxorubicin for cancer therapy

PolySciTech (www.polyscitech.com) provides a wide variety of mPEG-PLA copolymers for drug delivery in the polyvivo brand line. Recently these types of polymers were utilized for the simultaneous delivery of chemotherapeutic doxorubicin and gemcitabine to tumor cells and the combined efficacy was observed to be synergistic indicating a potential for this system to improve cancer treatment. Read more: Liu, Dechun, Yanbin Chen, Xiaoshan Feng, Miao Deng, Gangqiang Xie, Jianguang Wang, Like Zhang, Qipeng Liu, and Pengfei Yuan. “Micellar nanoparticles loaded with gemcitabine and doxorubicin showed synergistic effect.” Colloids and Surfaces B: Biointerfaces 113 (2014): 158-168. http://www.sciencedirect.com/science/article/pii/S0927776513005158

“Highlights: Gemcitabine and doxorubicin were separately conjugated to biodegradable polyesters. The two drug conjugates can be mixed at desirable ratio and self-assembled into micelles M(Gem/Dox) with both gemcitabine and doxorubicin. M(Gem/Dox) displayed controlled drug release and synergism in vitro. Abstract: Gemcitabine and doxorubicin were separately chemically linked to biodegradable polymers to prepare polymer–gemcitabine and polymer–doxorubicin conjugates. Moreover, the two conjugates can self-assemble into micelles with both gemcitabine and doxorubicin. In this way, the two anticancer drugs were combined. The in vitro MTT assay with these combined drugs showed synergistic effect compared to single use of each drug.”

Liu, 2014 dox-Gem

mPEG-CPLA for intracellular RNA/DNA delivery

PolySciTech (www.polyscitech.com) provides Methoxy Poly(ethylene glycol)-b-poly(lactide-co-allyl lactide-co-thiolene conjugated diethylaminoethyl-lactide) (mPEG-CPLA, PolyVivo AI 74) which is precursor agent to crosslinked miniemulsions recently used for RNA/DNA delivery. Read more: Zou, Jiong, Chyi Chin Hew, Efrosyni Themistou, Yukun Li, Chih,Kuang Chen, Paschalis Alexandridis, and Chong Cheng. “Clicking Well Defined Biodegradable Nanoparticles and Nanocapsules by UV Induced Thiol Ene CrossLinking in Transparent Miniemulsions.” Advanced Materials 23, no. 37 (2011): 4274-4277. http://onlinelibrary.wiley.com/doi/10.1002/adma.201101646/full

 

“A novel approach for the preparation of nanomaterials is developed by tuning miniemulsion reaction systems to be transparent in order to enable highly efficient photoreactions. Biodegradable nanoparticles and nanocapsules are obtained by UV-induced thiol-ene cross-linking of polylactide (PLA)-based precursor polymers preassembled in transparent miniemulsions. These well-defined nanomaterials may potentially serve as ideal scaffolds for drug delivery.”

Jong, 2011 mPEG-CPLA

PolySciTech “Shirts for Students” at 2014 CRS meeting

PolySciTech (www.polyscitech.com) is your source for custom laboratory reagents and research polymer products especially PEG-PLGA, thermogels, and reactive endcapped polymers. School is tough and we know it. That’s why we will be handing out FREE PolySciTech T-shirts to students at this year’s annual Controlled Release Society (CRS) meeting in Chicago, IL.  Supplies are limited so come by early.  Be the envy of your lab in your very own PST shirt.

Image shows our very own intern and graduate student, Frances Knight, modeling a PST shirt.

PolySciTech Shirt

PolySciTech at 2014 CRS meeting

PolySciTech (www.polyscitech.com) will be exhibiting at this years controlled release society (CRS) annual meeting (http://www.controlledreleasesociety.org/meetings/annual/Pages/default.aspx) at booth #707. Come on over and check us out to learn more about our polymers and other offerings. We will be handing out free T-shirts to students (while supplies last).

T-shirts PST