Monthly Archives: October 2014

PLGA-PEG-PLGA thermogel used for osterosarcoma treatment

PolySciTech (www.polyscitech.com) provides a wide variety of PLGA-PEG-PLGA triblock thermogels for use as drug delivery depots. Recently researchers have utilized similar polymers to deliver SiRNA and doxorubicin to osterosarcoma cells successfully inducing apoptosis both in-vitro and in nude mice. Read more: Ma, Hecheng, Chaoliang He, Yilong Cheng, Dongsong Li, Yubao Gong, Jianguo Liu, Huayu Tian, and Xuesi Chen. “PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment.” Biomaterials 35, no. 30 (2014): 8723-8734. http://www.sciencedirect.com/science/article/pii/S0142961214007510

“Abstract: Combination cancer therapy has emerged as crucial approach for achieving superior anti-cancer efficacy. In this study, we developed a strategy by localized co-delivery of PLK1shRNA/polylysine-modified polyethylenimine (PEI-Lys) complexes and doxorubicin (DOX) using biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for treatment of osteosarcoma. When incubated with osteosarcoma Saos-2 and MG-63 cells, the hydrogel containing PLK1shRNA/PEI-Lys and DOX displayed significant synergistic effects in promoting the apoptosis of osteosarcoma cells in vitro. After subcutaneous injection of the hydrogel containing PLK1shRNA/PEI-Lys and DOX beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts, the hydrogels exhibited superior antitumor efficacy in vivo compared to the hydrogels loaded with PLK1shRNA/PEI-Lys or DOX alone. It is noteworthy that the combination treatment in vivo led to almost complete suppression of tumor growth up to 16 days, significantly enhanced PLK1 silencing, higher apoptosis of tumor masses, as well as increased cell cycle regulation. Additionally, ex vivo histological analysis of major organs of the mice indicated that the localized treatments showed no obvious damage to the organs, suggesting lower systemic toxicity of the treatments. Therefore, the strategy of localized, sustained co-delivery of PLK1shRNA and DOX by using the biodegradable, injectable hydrogel may have potential for efficient clinical treatment of osteosarcoma. Keywords: Combination therapy; PLK1 silencing; Synergistic effect; Localized delivery; Injectable hydrogel; Osteosarcoma”

Mal-PEG-PLA for generation of CLT1 targeted nanoparticles as treatment for brain cancer

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers including reactive endcapped maleimide-PEG-PLA and PLGA type copolymers. The maleimide functionality allows for conjugation to thiol in pH neutral aqeous solution allowing for peptide/protein conjugation. Recently this was utilized to generate a nanoparticle which has a peptide targeting moiety towards brain cancer cells. It was found that this nanoparticle successfully delivered chemotherapeutic paclitaxel to these cells in mouse test. Read more: Zhang, Bo, Shun Shen, Ziwei Liao, Wei Shi, Yu Wang, Jingjing Zhao, Yue Hu et al. “Targeting fibronectins of glioma extracellular matrix by CLT1 peptide-conjugated nanoparticles.” Biomaterials 35, no. 13 (2014): 4088-4098. http://www.sciencedirect.com/science/article/pii/S0142961214000623

 

“Abstract: The abundant extracellular matrix (ECM) in the glioma microenvironment play a critical role in the maintenance of glioma morphology, glioma cells differentiation and proliferation, but little has been done to understand the feasibility of ECM as the therapeutic target for glioma therapy. In this study, a drug delivery system targeting fibronectins (FNs), a prevailing component in the ECM of many solid tumors, was constructed for glioma therapy based on the interaction between the abundant FNs in glioma tissues and the FNs-targeting moiety CLT1 peptide. CLT1 peptide was successfully conjugated to PEG-PLA nanoparticles (CNP). FNs were demonstrated to be highly expressed in the ECM of glioma spheroids in vitro and glioma tissues in vivo. CLT1 modification favored targeting nanoparticles penetration into the core of glioma spheroids and consequently induced more severe inhibitive effects on glioma spheroids growth than traditional NP. In vivo imaging, ex vivo imaging and glioma tissue slides showed that CNP enhanced nanoparticles retention in glioma site, distributed more extensively and more deeply into glioma tissues than that of conventional NP, and mainly located in glioma cells rather than in extracellular matrix as conventional NP. Pharmacodynamics outcomes revealed that the median survival time of glioma-bearing mice models treated with paclitaxel-loaded CNP (CNP-PTX) was significantly prolonged when compared with that of any other group. TUNEL assay demonstrated that more extensive cell apoptosis was induced by CNP-PTX treatment compared with other treatments. Altogether, these promising results indicated that this ECM-targeting drug delivery system enhanced retention and glioma cell uptake of nanoparticles and might have a great potential for glioma therapy in clinical applications. Keywords: Extracellular matrix; Fibronectin; Targeting; Nanoparticles; Glioma; Retention”

New publication utilizes Mal-PEG-PLGA from PolySciTech for generating Her2 targeted, RNAse delivering, nanoparticle for cancer therapy.

PolySciTech (www.polyscitech.com) provides a wide array of Maleimide-PEG-PLGA and other reactive intermediates. Recently published PhD thesis of Neda Samadi from Utrecht University utilized Polyvivo AI20 to generate nanoparticles labelled with 11A4 protein for Her2 targeting and used these nanoparticles to deliver RNAse to tumor cells. Alone RNAse is innefective at preventing cancer cell growth but when encapsulated in the delivery system an IC50 of only 5uM was observed. Read more with full-text available here: Samadi, Neda, Marta M. Kijanka, Sabrina Oliveira, Tina Vermonden, Cornelus F. van Nostrum, Maryam Amidi, Paul MP van Bergen en Henegouwen, and W. E. Hennink. “Nanobody-Targeted and RNase-Loaded Nanoparticles Based on a Hydrophilic Polyester Aimed for Cancer Therapy.” Biodegradable Nanoparticles Based on Aliphatic Polyesters; Towards Targeted Intracellular Delivery of Protein Therapeutics: 117. http://dspace.library.uu.nl/bitstream/handle/1874/292552/samadi.pdf?sequence=2#page=117

“Abstract: The aim of this study was to develop a nanomedicine based on a hydrophilic polyester (poly lactic-co-glycolic-co-hydroxymethyl glycolic acid; PLGHMGA) for targeted delivery of RNase A as a modality for cancer treatment. RNase-loaded pegylated PLGHMGA nanoparticles (NPs) of ~280 nm were prepared by a double emulsion solvent evaporation method. Encapsulated RNase was almost completely released within 12 days and it was shown that the enzymatic activity of the released protein was fully preserved. Ten % Maleimide-PEG-PLGA was added to the formulation to graft the Her2 targeted nanobody (11A4) at the surface of the NPs to render them specific for breast cancer cells. Alexa Fluor 532 labeled 11A4-decorated NPs showed substantially higher binding to and uptake by Her2 over-expressing cancer cells (Skbr3) than particles without nanobody. Interestingly, no binding of the nanobody-conjugated particles was observed onto Her2 negative cells (MDA-MB-231). The RNase-loaded 11A4-NPs exhibited a dose-dependent cytotoxicity with an IC50 of 5 μM, whereas free RNase was ineffective up to 100 μM. These results demonstrate that nanobody conjugated PLGHMGA NPs are promising carriers for targeted delivery of RNase.”

Halloween Special: Spooky 13% Discount on PolySciTech Polymers

PolySciTech is your source for “hard-to-find” and unique polymer products as well as a wide array of biodegradable polyesters, block copolymers, fluorescently tagged polymers, and reactive intermediates. In celebration of Halloween PolySciTech (www.polyscitech.com) is offering a 13% discount on 13 select products. From October 15-31st 2014 use the discount code “SPOOKY13” to get an extra 13% off the following products. 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); AP052 PLGA LG 85:15 acid endcap  (Mn 200,000-300,000 Da) (L-lactide); and AP017 PLGA LG 60:40 acid endcap  (Mn 75,000-85,000 Da).

Spooky discount

PLGA-PEG-PLGA used to deliver chemotherapeutic andrographolide

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers including triblock PLGA-PEG-PLGA. Recently PLGA-PEG-PLGA was utilized to generate a micelle delivery system for poorly soluble Andrographolide. Read more: Zhang, Jinming, Yingbo Li, Wei Gao, Michael A. Repka, Yitao Wang, and Meiwan Chen. “Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy.” Expert opinion on drug delivery 0 (2014): 1-14. http://informahealthcare.com/doi/abs/10.1517/17425247.2014.924503

“Abstract: Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo. Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat. Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension. Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy. Keywords andrographolide, breast cancer MAD-MB-231 cells, micelles, pharmacokinetics, poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) triblock copolymer”