Monthly Archives: May 2014

PLGA-PEG for cancer diagnostics

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA block copolymers. Recently these types of polymers have been applied to developing cancer diagnostic delivery systems by loading perfluorooctyl bromide (Ultrasound/MRI contrast agent).  Read more: Diou, O., E. Fattal, T. Payen, S. L. Bridal, J. Valette, and N. Tsapis. “Nanocapsules of perfluorooctyl bromide for theranostics: from formulation to in vivo targeting.” In SPIE BiOS, pp. 895514-895514. International Society for Optics and Photonics, 2014. http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=1852594

“Abstract: The need to detect cancer at its early stages, as well as, to deliver chemotherapy to targeted site motivates many researchers to build theranostic platforms which combine diagnostic and therapy. Among imaging modalities, ultrasonography and Magnetic Resonance Imaging (MRI) are widely available, non invasive and complement each other. Both techniques often require the use of contrast agents. We have developed nanocapsules of perfluorooctyl bromide as dual contrast agent for both imaging modalities. The soft, amorphous polymer shell provides echogenicity, while the high-density perfluorinated liquid core allows detection by 19F MRI. We have used a shell of poly(lactide-co-glycolide) (PLGA) since this polymer is biodegradable, biocompatible and can be loaded with drugs. These capsules were shown to be efficient in vitro as contrast agents for both 19F MRI and ultrasonography. In addition, for in vivo applications a poly(ethyleneglycol) (PEG) coating promotes stability and prolonged circulation. Being stealth, nanocapsule can accumulate passively into implanted tumors by the EPR effect. We will present nanocapsule formulation and characterization, and will show promising in vivo results obtained for both ultrasonography and 19F MRI Topics: Cancer ; Coating ; Diagnostics ; Magnetic resonance imaging ; Polymers ; Ultrasonography”

Amine endcapped PLGA/PLA for improved blood compatibility

PolySciTech (www.polyscitech.com) provides a wide array of amine endcapped PLGA’s, PLA’s, and PCL’s.  The effect of amine endcapping is that these polymers can react easily with a variety of chemistries notably carbodiimide/NHS type reactions. Recently this type of polymer and reaction was utilized to attach heparin to PLA surface to improve hemocompatibility. Read more: Sharkawi, Tahmer, Vincent Darcos, and Michel Vert. “Poly (DL‐lactic acid) film surface modification with heparin for improving hemocompatibility of blood contacting bioresorbable devices.” Journal of Biomedical Materials Research Part A 98, no. 1 (2011): 80-87. http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.33099/full

“Abstract: This work describes a simple method to immobilize heparin by covalent bonding to the surface of poly(lactic acid) film with the aim of showing improved hemocompatibility. Carboxyl groups present in heparin molecules were activated by reaction with N-hydroxy-succinimide and allowed to react with free amino groups created at the surface of poly(dl-lactic acid) films by controlled aminolysis. Contact angle measurements and XPS analysis confirmed the binding. Quantification was determined by radioactivity using heparin labeled with tritium. The surface exhibited anti factor Xa activity, thus confirming the presence of bounded heparin that kept some biological activity. Finally platelets adhesion showed less platelet adhesion on heparin modified films as well as preserved morphology. Keywords: poly(lactic acid);surface modification;heparin immobilization;hemocompatibility;platelet adhesion;bioresorbable;cardiovascular medical device”

Pep-1 targeted nanoparticles for brain cancer treatment

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA and related activatable polymers.  Recently these types of poylmers have been utilized to generate a system for delivering drugs to glioma cells via Pep-1/IL-13Ra2 binding. Read more: Wang, Baoyan, Lingyan Lv, Zhongyuan Wang, Yue Zhao, Lin Wu, Xiaoling Fang, Qunwei Xu, and Hongliang Xin. “Nanoparticles functionalized with Pep-1 as potential glioma targeting delivery system via interleukin 13 receptor α2-mediated endocytosis.” Biomaterials 35, no. 22 (2014): 5897-5907. http://www.sciencedirect.com/science/article/pii/S0142961214003287

“Abstract: The treatment for glioma is one of the most challenging problems and therapeutic effect of glioma is often limited due to poor penetration into the tumor tissue. Interleukin 13 receptor α2 (IL-13Rα2) is over-expressed on tumor including established glioma cell lines and primary glioblastoma cell cultures. However, it will not cause activation of its signaling pathways. So it could be served as a promising targeted moiety for anti-glioma drug delivery. Pep-1, one specific ligand of IL-13Rα2, was identified to exhibit excellent capacity of crossing the blood tumor barrier (BTB) and homing to giloma. In this study, based on the IL-13Rα2-mediated endocytosis, Pep-1 was exploited as a potential ligand for effective glioma-targeting delivery. Pep-1 was functionalized to the surface of PEG-PLGA nanoparticles (Pep-NP) to evaluate its glioma homing, by taking advantage of the excessive expression of the IL-13Rα2 on the surface of glioma cells. Compared with non-targeting nanoparticles, Pep-NP exhibited a significantly enhanced cellular association in rat C6 glioma cells and improved penetration in 3D avascular C6 glioma spheroids. Following intravenous administration, Pep-NP could facilitate the distribution of the coumarin-6 in vivo glioma region, 2.21 times higher than that of NP for quantitative analysis. In conclusion, the Pep-NP could precisely target to the brain glioma, which was a potential targeting drug delivery system for glioma treatment. Keywords: Glioma; Blood tumor barrier (BTB); Interleukin 13 receptor α2; Pep-1 peptide; Targeting nanoparticles”

PEG-PLGA for diabetes treatment

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLGA copolymers.  Recently it has been found that PEG-PLGA forms into a pH sensitive complex with insulin which protects the insulin from low pH potentially allowing for it to be taken orally rather than injected. Read more:  Hosseininasab, Sara, Roghiyeh Pashaei‐Asl, Amir Ahmad Khandaghi, Hamid Tayefi Nasrabadi, Kazem Nejati‐Koshki, Abolfazl Akbarzadeh, Sang Woo Joo, Younes Hanifehpour, and Soodabeh Davaran. “Synthesis, characterization, and In vitro studies of PLGA‐PEG nanoparticles for oral Insulin delivery”. Chemical biology & drug design (2014). http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12318/abstract

 

“Abstract: Therapeutic proteins and peptides are corresponding to a major area of research in biotechnology companies and current pharmaceutical. Because of their natural instability, the enormous majority of these drugs require parenteral administration. Oral insulin delivery would be a highly attractive alternative process of administration, though it continues to be a mysterious target due to the enzymatic digestion of insulin and low levels of absorption from the gastrointestinal region. Hydrogel polymers can be considered as potential carriers for oral insulin delivery. In particular, a pH responsive hydrogel composed of PLGA-PEG has shown the ability to protect insulin from enzymes in the gastric environment and release in small intestines. However, this material has not shown similar potential for oral protein delivery of further model drugs. To date, the unique interaction between PLGA-PEG and insulin, as a potential drug for oral delivery, is not completely understood. The focus of this research is synthesization and characterization of hydrogels PLGA-PEG insulin nanoparticles; also pH-sensitivity of insulin nanoparticles was investigated. Keywords: PLGA-PEG insulin;Oral delivery;pH-sensitivity”

PLA mechanical property improvement by PLA-PEG-PLA

PolySciTech (www.polyscitech.com) provides a wide variety of biodegradable polymers including PLLA and P(DL)La-PEG-P(DL)La triblock. Recently these kinds of polymers were utilized to generate high tensile strength/heat resistant materials due to synergistic effects between PLA and PEG block.  Read more: Liu, Yanlong, Jun Shao, Jingru Sun, Xinchao Bian, Lidong Feng, Sheng Xiang, Bin Sun, Zhiming Chen, Gao Li, and Xuesi Chen. “Improved mechanical and thermal properties of PLLA by solvent blending with PDLA-b-PEG-b-PDLA.” Polymer Degradation and Stability (2014). http://www.sciencedirect.com/science/article/pii/S0141391014000251

“Abstract: In this article, two types of poly (d-lactide)-b-poly (ethylene glycol)-b-poly (d-lactide) (PDLA-b-PEG-b-PDLA) were added into PLLA matrix by solution casting method. The obtained films were characterized by wide-angle X-ray diffractomery (WAXD), differential scanning calorimetry (DSC), tensile testing and thermal gravimetric analyzer (TGA). Results indicated that the heat resistance of these blends could be improved when the amount of copolymer exceeded 30 wt%, because the high melting point stereocomplex was preferentially formed at that addition amount, whenever from solutions or from melt. Both the tensile strength and elongation at break of the blends were enhanced when 30 wt% copolymer was added, which were partly caused by the synergistic effects of stereocomplexation between enantiomeric PLAs and plasticization of PEG blocks. The blends showed higher thermal stability than neat PLLA at temperature above 370 °C. These results showed that the toughness and heat resistance of PLLA were improved, which made the application of PLA probable. Keywords: Poly (lactic acid); Stereocomplex; Mechanical properties; Thermal stability”

iNGR-PEG-PLGA nanoparticles for treatment of brain cancer

PolySciTech (www.polyscitech.com) provides a wide array of actiavatable PLGA-PEG copolymers including PLGA-PEG-COOH which can be conjugated to amines by carbodiimide techniques. Recent research has shown that a similar polymer can be conjugated to iNGR peptide and formulated into a paclitaxel nanoparticle which has preferential targeting towards brain tumors. Read more: Kang, Ting, Xiaoling Gao, Quanyin Hu, Di Jiang, Xingye Feng, Xue Zhang, Qingxiang Song et al. “iNGR-modified PEG-PLGA nanoparticles that recognize tumor vasculature and penetrate gliomas.” Biomaterials 35, no. 14 (2014): 4319-4332. http://www.sciencedirect.com/science/article/pii/S0142961214001264

“Abstract: A major cross-cutting problem for glioma therapy is the poor extravasation and penetration of the payload drug in target glioma parenchyma. Here, to overcome these obstacles, a tumor vessel recognizing and tumor penetrating system is developed by functionalizating the poly (ethyleneglycol)-poly (l-lactic-co-glycolic acid) nanoparticles with an iNGR moiety (iNGR-NP). The nanoparticulate formulation is expected to achieve specific deep penetration in the tumor tissue by initially binding to aminopeptidase N, with iNGR proteolytically cleaved to CRNGR, and then bind with neuropilin-1 to mediate deep penetration in the tumor parenchyma. iNGR-NP exhibits significantly enhanced cellular uptake in human umbilical vein endothelial cells, improves the anti-proliferation and anti-tube formation abilities of paclitaxel in vitro. Following intravenous administration, iNGR-NP present favorable pharmacokinetic and tumor homing profiles. Glioma distribution and penetration assays confirm that iNGR-NP achieve the highest accumulation and deepest penetration at the glioma sites. The anti-glioma efficacy of paclitaxel-loaded iNGR-NP is verified by its improved anti-angiogenesis activity and the significantly prolonged survival time in mice bearing intracranial glioma. These evidences highlight the potential of iNGR-decorated nanoparticles in overcoming the leading edge problem in anti-glioma drug delivery. Keywords: iNGR peptide; Drug delivery; Nanoparticles; Penetration; Glioma therapy”

CD44 labelled PEG-PLGA for ovarian cancer treatment

PolySciTech (www.polyscitech.com) provides a wide variety of PEG-PLGA copolymers including PLGA-PEG-Maleimide similar to that used in a recent study to create CD44 labelled nanoparticles for targeted drug delivery to ovarian cancer cells. Read more: Bai, Meng-Yi, and Sheng-Zhong Liu. “A simple and general method for preparing antibody-PEG-PLGA sub-micron particles using electrospray technique: An in vitro study of targeted delivery of cisplatin to ovarian cancer cells.” Colloids and Surfaces B: Biointerfaces 117 (2014): 346-353. http://www.sciencedirect.com/science/article/pii/S0927776514001246

“Abstract: Cisplatin-encapsulating maleimide-polyethylene glycol- Poly(d,l-lactic-co-glycolide) (cis-encapsulating mal-PEG-PLGA) particles were produced using the electrospray technique and bioconjugated with CD44 monoclonal antibody, targeting the counterpart receptor. The produced suspension of cis-encapsulating CD44-PEG-PLGA particles contains an antibody loading of 12.65–15.17 μg/mL and efficiently targets a CD44-overexpressed ovarian cancer cell line, such as CP70 and SKOV-3, within 6 h of treatment, which was determined by Bradford assay, immunofluorescence analysis, and confocal laser scanning microscopic (CLSM) study. Most importantly, no tedious multi-step bioconjugation procedures are needed to synthesize mal-PEG-PLGA vehicles for antibody and drug loading, avoiding the undesirable hydrolysis of mal-PEG moiety and so successfully generating the cis-encapsulating mal-PEG-PLGA particles within one step. After conjugation of the CD44 antibody, the produced cis-encapsulating CD44-PEG-PLGA particles exhibited a better anti-proliferative ability against ovarian cancer cells compared to free form of cisplatin and PLGA particles without CD44 conjugation. Notably, the cis-encapsulating CD44-PEG-PLGA particles have approximately 10-14% greater the anti-proliferative ability against CP70 and SKOV-3 cells at a concentration of 1.25 μM, which falls within the concentrations used in chemotherapy. The proposed antibody-functionalization strategy represents an excellent platform for preparing particles with targeting ability in cancer therapy in vitro or in vivo. Highlights: We report a simple method for preparing antibody-PEG-PLGA particles using electrospray. Particles were produced using the electrospray system and bioconjugated with CD44 antibody. The cis-encapsulating CD44-PEG-PLGA particles contain an antibody loading of 12.65–15.17 μg/mL. The cis-encapsulating CD44-PEG-PLGA particles against CP70 and SKOV-3 cells were improved by 10–14%. Keywords Electrospray; Nanotechnology; Controlled release; Drug delivery; Biomaterials.”

Bai, 2014 CD44 nanoparticles

PEG-PLA used for delivery of peptide drug for cancer treatment

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA copolymers under the polyvivo brand name. Recently this type of copolymer has been utilized to delivery NuBCP-9 anti-cancer peptide to cancer cells triggering apoptosis. Read more: Kumar, Manoj, Dikshi Gupta, Gurpal Singh, Sapna Sharma, Madhusudan Bhatt, C. K. Prashant, A. K. Dinda, Surender Kharbanda, Donald Kufe, and Harpal Singh. “Novel polymeric nanoparticles for intracellular delivery of peptide cargos: antitumor efficacy of the Bcl-2 conversion peptide NuBCP-9.” Cancer research (2014): canres-2015. http://cancerres.aacrjournals.org/content/early/2014/04/16/0008-5472.CAN-13-2015.short

“Abstract: The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacological properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anti-cancer peptide NuBCP-9 which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles (NPs) comprised of a polyethylene glycol (PEG)-modified polylactic acid diblock copolymer (NuBCP-9/PLA-PEG), or PEG-polypropylene glycol-PEG-modified PLA – tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the NPs was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these NPs in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/NPs triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins.”

PNIPAM-co-AA for Glaucoma treatment

PolySciTech (www.polyscitech.com) provides poly(n-isopropylacrylamide-co-acrylic acid) (NIPAM-co-AA) as thermogelling polyvivo AO14. Recently similar polymers have been utilized to control the delivery of anti-glaucoma drug, epinephrine.  Read more: Prasannan, Adhimoorthy, Hsieh-Chih Tsai, Yu-Shuan Chen, and Ging-Ho Hsiue. “Thermal-trigger in situ hydrogel from poly (acrylic acid-co-N-isopropylacrylamide) for controlled release of antiglaucoma drug.” Journal of Materials Chemistry B (2014). http://pubs.rsc.org/EN/content/articlehtml/2014/tb/c3tb21360a

 

“Abstract: The purpose of this study was to develop and evaluate thermally responsive copolymers, which contain temperature- and pH-sensitive segments that are either alternating in or grafted onto the main chain, and to exploit their temperature-sensitive properties for ophthalmic drug delivery. Accordingly, two types of thermoresponsive copolymers—a linear poly(acrylic acid-co-N-isopropylacrylamide) random copolymer (PAAc-co-PNIPAAm) and a poly(acrylic acid-g-N-isopropylacrylamide) graft copolymer (PAAc-g-PNIPAAm)—were investigated for their thermosensitive in situ gel formation and potential applications for ophthalmic drug delivery. All the PAAc-g-PNIPAAm graft copolymers, and the linear PAAc-co-PNIPAAm copolymer with low acrylic acid contents, have an LCST of 34 °C; this is close to the surface temperature of the eye and can therefore be utilized for ophthalmic drug delivery. In addition, the PAAc-g-PNIPAAm graft copolymers showed a higher water content than the linear random copolymer; this is due to the high water adsorption ability of PAAc. The drug release dynamics of [3H]-epinephrine as a model showed that the linear random copolymer has a faster drug release, while the graft copolymers showed a more sustained release profile. The Ritger–Peppas model was used to account for the release of the epinephrine diffusion exponent ‘n’ which was in between 0.5 and 0.6. The release of the drug is considered mainly dependent on diffusion but other factors cannot be excluded. We suspected that the dynamics of drug release are determined by the water adsorption ability because high water content results in the formation of a larger capillary network in the polymer matrix, which promotes drug diffusion into the copolymer. The results suggest that PAAc-g-PNIPAAm graft copolymers are potential thermosensitive in situ gel-forming materials for ophthalmic drug delivery.”