Monthly Archives: February 2014

Dox-PLA-PEG-Fol for cancer treatment

PolySciTech (www.polyscitech.com) provides several PLA-PEG-COOH and PLGA-PEG-COOH precursors/reactive intermediates (e.g. PolyVivo AI37, AI54, AI34 AI56, etc.) for a wide variety of drug delivery applications. Recently similar polymers have been utilized as a precursor towards synthesis of docetaxel conjugated PLA-PEG-Folate polymers which displayed effectiviness against cancer cells in-vitro. Read more at: Hami, Zahra, Mohsen Amini, Mahmoud Ghazi-Khansari, Seyed Mehdi Rezayat, and Kambiz Gilani. “Synthesis and in vitro evaluation of a pH-sensitive PLA-PEG-Folate based polymeric micelle for controlled delivery of docetaxel.” Colloids and Surfaces B: Biointerfaces (2014). http://dx.doi.org/10.1016/j.colsurfb.2014.01.015

“Abstract:  pH-responsive docetaxel-conjugated poly (lactic acid) (PLA)–polyethyleneglycol (PEG) micellar formulation was synthesized via acid labile hydrazone linkage. Levulinic acid (LEV) was used as a linker between docetaxel (DTX) and hydrazine. Targeted delivery of DTX was achieved by conjugation of folate to PEG segment. The DTX conjugated polymeric micelles were about 181 nm in diameter and their critical micelle concentration was 5.18 μg/ml. DTX was released from micelles in a pH-dependent manner. The results showed a significant difference in DTX release from polymeric micelles at pH 5.0 and pH 7.4. Cytotoxicity assays using methyl tetrazolium (MTT), neutral red (NR) and lactate dehydrogenase (LDH) demonstrated a decreased cytotoxic activity of the drug containing nanoconjugate compared with free DTX that appears to be contributed to the sustained release of drug from micelles. Based on these results, it is expected that this pH-responsive nanoconjugate is promising as a useful carrier for targeted delivery of anticancer agents.”Hami 2014 DTX-PLA-PEG-Fol

Gold Nanoparticles as Vaccine Adjuvant

PolySciTech (www.polyscitech.com) provides gold nanoparticle products including polyvivo AO40 (25nm colloidal gold).  Recent research has shown that,, in addition to many other uses, gold nanoparticles elicit immune responses allowing for their application to vaccine technology as an adjuvant. Read more at: Wang, Yong-Tang, Xiu-Min Lu, Feng Zhu, and Min Zhao. “The preparation of gold nanoparticles and evaluation of their immunological function effects on rats.” Bio-medical materials and engineering 24, no. 1 (2014): 885-892. http://iospress.metapress.com/content/a396n07862218037/

 

 

“Abstract: As a new type of biomaterials, gold nanoparticles (GNPs), also known as colloidal gold (CG), have a wide biomedical application. In this study, GNPs with diameters of 10, 15, and 25 nm were prepared by sodium citrate reduction, and detected by common optical property, ultraviolet-visible (UV-vis) absorbance spectroscopy, and scanning electron microscope (SEM), separately for identification of the particle size and uniformity. In order to observe the effects of GNPs on immune function, adult Sprague Dawley (SD) rats were immunized with the above three GNPs, each having three doses of 0.2, 0.4, and 0.6 ml, and rats without immunization served as negative control. After immunization, proliferation activity of blood and spleen lymphocyte and the levels of interleukin-2 (IL-2) in serum and supernatant of spleen lymphocyte were detected by thiazoleblue (MTT) assay and enzyme linked immunosorbent assay (ELISA), respectively. The results indicated that different size of GNPs was prepared, and the uniformity increased with the decrease of the size of particles. Different diameters and doses of GNPs have different effects on proliferation of blood and spleen lymphocyte, as well as the levels of IL-2 in serum and supernatant of spleen lymphocyte. The 15 nm CG in 0.6 ml dose group could most significantly promote blood and spleen lymphocyte proliferation, and enhance IL-2 levels in serum and supernatant of spleen lymphocyte. Taken together, the findings revealed that application of CG prepared by sodium citrate reduction could enhance specific and nonspecific immune responses, and the 0.6 ml dose of 15 nm CG might be the best immunizing dose in rats. This fact may serve as a further evidence for using CG as a novel immunoadjuvant in the future.

Thermogel review

PolySciTech (www.polyscitech.com) offers a variety of biodegradable thermogel polymers including PLGA-PEG-PLGA (e.g. PolyVivo AK12, AK24) as well as thermogelling chitosan derivatives (Kito-6).  Thermogelling polymers and their potential clinical applications were the topic of a recent review paper. Read more at: Dou, Qing Qing, Sing Shy Liow, Enyi Ye, Rajamani Lakshminarayanan, and Xian Jun Loh. “Biodegradable Thermogelling Polymers: Working Towards Clinical Applications.” Advanced Healthcare Materials (2014). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201300627/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false

“Abstract: As society ages, aging medical problems such as organ damage or failure among senior citizens increases, raising the demand for organ repair technologies. Synthetic materials have been developed and applied in various parts of human body to meet the biomedical needs. Hydrogels, in particular, have found extensive applications as wound healing, drug delivery and controlled release, and scaffold materials in the human body. The development of the next generation of soft hydrogel biomaterials focuses on facile synthetic methods, efficacy of treatment, and tunable multi-functionalities for applications. Supramolecular 3D entities are highly attractive materials for biomedical application. They are assembled by modules via various non-covalent bonds (hydrogen bonds, p–p stacking and/or van der Waals interactions). Biodegradable thermogels are a class of such supramolecular assembled materials. Their use as soft biomaterials and their related applications are described in this Review. Keywords: thermogel;drug delivery;tissue engineering;biodegradable;biomedical”

PCL-PEG-PCL for reduced post-surgical adhesion

PolyScitech (www.polyscitech.com) provides triblock PCL-PEG-PCL block copolymers (e.g. polyvivo AK35 etc.). Recently similar polymers have been utilized to generate thermosensitive micelles which act to reduce postoperative adhesion. Read more at: Wu, Qinjie, Ling Li, Ning Wang, Xiang Gao, Bilan Wang, Xinyu Liu, Zhiyong Qian, Yuquan Wei, and Changyang Gong. “Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.” International journal of nanomedicine 9 (2014): 727. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921091/

“Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL–PEG–PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1±2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58±0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67±0.78; P<0.001, Mann–Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL–PEG–PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions. Keywords: postsurgical adhesion, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL), surgical complications, barrier agent”

Publication uses Akina products for intranasal treatment of schizophrenia

New publication out using PolySciTech (www.polyscitech.com) products. Recent paper published by Piazza et. al. utilizes a combination of methoxy-PEG-PLGA and Mal-PEG-PLGA as precursors for generating Solanum tuberosum lectin conjugated nanoparticles capable of intranasally delivering haloperidol to the brain as a potential treatment for schizophrenia.  Read more at: Piazza, Justin, Todd Hoare, Luke Molinaro, Kristen Terpstra, Jayant Bhandari, P. Ravi Selvaganapathy, Bhagwati Gupta, and Ram K. Mishra. “Intranasally Administered Lectin Functionalized poly (ethylene glycol)–block-poly (D, L)-lactic-co-glycolic acid (PEG-PLGA) Nanoparticles for the Treatment of Schizophrenia.”European Journal of Pharmaceutics and Biopharmaceutics (2014). http://dx.doi.org/10.1016/j.ejpb.2014.02.007

“Abstract: Lectin-functionalized, polyethylene glycol–block-poly-(d,l)-lactic-co-glycolic acid nanoparticles loaded with haloperidol were prepared with narrow size distributions and sizes <135 nm. The nanoparticles exhibited high Solanum tuberosum lectin (STL) conjugation efficiencies, encapsulation efficiencies, and drug loading capacities. The in vitro release of haloperidol was 6–8% of the loaded amount in endo-lysosomal conditions over 96 h, demonstrating minimal drug leakage and the potential for the efficient drug transport to the targeted brain tissue. The haloperidol released upon erosion was successful in displacing [3H] N-propylnorapomorphine and binding to bovine striatal dopamine D2 receptors. Both haloperidol-loaded nanoparticle formulations were found to be highly effective at inducing catalepsy. Intranasal administration of STL-functionalized nanoparticles increased the brain tissue haloperidol concentrations by 1.5–3-fold compared to non-STL-functionalized particles and other routes of administration. This formulation demonstrates promise in the reduction in the drug dose necessary to produce a therapeutic effect with antipsychotic drugs for the treatment of schizophrenia.”Slide 1

PolyVivo AP34 tensile properties

PolySciTech (www.polyscitech.com) provides PolyVivo AP34 Poly(caprolactone-co-DL-lactide) (LA:CL 1:99) (Mn 45,000-55,000 Da). Recent mechanical testing at Akina, Inc. indicates this material has an elastic modulus (2% strain) of 649 kPa. The ultimate yield strain was 48% and tensile strength was found to be 8MPa. Testing done on a dogbone cut section using TA.XTplus texture analyzer.

PolyVivo AO19 dual sensitivity to pH and temperature

 

PolySciTech (www.polyscitech.com) provides PolyVivo AO19 Poly(dimethylaminoethyl methacrylate-co-methoxy polyethylene glycol) P(DMAEMA-mPEG) (95:5). Recent testing at Akina confirmed that this polymer, when dissolved in water, has sensitivity towards both temperature as well as pH of the aqeous environment. The material degels at low pH due to ionization of the DMAEMA endgroup.  Find out more here:  AO19PHTEMP

Thermogelling glycol chitin

PolySciTech (www.polyscitech.com) has thermogelling glycol chitin available (Kito-5). This biodegradable thermogel maintains a neutral pH during degradation allowing for use in sensitive areas.  Recently similar materials have been the focus of a review paper. Read more at: Kim, Jang Kyoung, Hyung Jin Kim, Jee-Young Chung, Jong-Hwan Lee, Seok-Beom Young, and Yong-Hee Kim. “Natural and synthetic biomaterials for controlled drug delivery.” Archives of pharmacal research 37, no. 1 (2014): 60-68. http://link.springer.com/article/10.1007/s12272-013-0280-6

“Abstract: A wide variety of delivery systems have been developed and many products based on the drug delivery technology are commercially available. The development of controlled-release technologies accelerated new dosage form design by altering pharmacokinetic and pharmacodynamics profiles of given drugs, resulting in improved efficacy and safety. Various natural or synthetic polymers have been applied to make matrix, reservoir or implant forms due to the characteristics of polymers, especially ease of control for modifications of biocompatibility, biodegradation, porosity, charge, mechanical strength and hydrophobicity/hydrophilicity. Hydrogel is a hydrophilic, polymeric network capable of imbibing large amount of water and biological fluids. This review article introduces various applications of natural and synthetic polymer-based hydrogels from pharmaceutical, biomedical and bioengineering points of view.”

Colloidal Gold Nanoparticles Now Available from PolySciTech

PolySciTech’s (www.polyscitech.com) newest product is PolyVivo AO40, 25nm sized uncoated gold nanoparticles in citrate buffer.  These blank particles are ready for modification via a wide range of techniques and can be used for imaging as well as drug delivery/therapeutic applications.  Recently similar nanoparticles have been conjugated to cell-penetrating peptides and used as a delivery system for doxorubicin in cancer therapy. Read more at: Park, Hyejin, Hiroshi Tsutsumi, and Hisakazu Mihara. “Cell-selective intracellular drug delivery using doxorubicin and α-helical peptides conjugated to gold nanoparticles.” Biomaterials (2014). http://dx.doi.org/10.1016/j.biomaterials.2013.12.094

“Abstract: Cell penetrating peptides (CPPs), which can enter a cell through the cell membrane, have potential research applications in the fields of drug delivery, gene therapy, and cancer therapy. However, CPPs are associated with problems such as low cell selectivity, low cell penetrating activity, and cell toxicity. To overcome the disadvantages of CPPs, we constructed a drug delivery system by developing 25 nm gold nanospheres (GNSs) conjugated to four α-helical CPPs from our peptide library. We examined the applicability of this cell-selective drug delivery system by evaluating its cell-penetrating and cell death activities and comparing them with those activities of the TAT peptide. Using the 25 nm GNS, we obtained higher cell death induction activity by the anti-cancer drug doxorubicin compared with our previous study using a 41 nm GNS. After entering the cell, the peptide-conjugated 25 nm GNS accumulated around the cell nucleus. High cell selectivity by α-helical CPP sequences was also demonstrated. Our results indicate that these α-helical peptide and 25 nm GNS conjugates are useful elements in an efficient cell-selective drug delivery system.”Au NP picture

PLGA-PEG-PLGA cyclodextrin hydrogels

PolySciTech (www.polyscitech.com) provides thermogelling PLGA-PEG-PLGA triblock copolymers including Polyvivo AK12 and AK24. Recently, similar polymers have been shown to form inclusion-complex based supramolecular hydrogels when interacting with cyclodextrin and that these hydrogels can be used for drug delivery. Read more at: Khodaverdi, Elham, Farnaz Sadat Mirzazadeh Tekie, Farzin Hadizadeh, Haydar Esmaeel, Seyed Ahmad Mohajeri, Sayyed A. Sajadi Tabassi, and Gholamhossein Zohuri. “Hydrogels Composed of Cyclodextrin Inclusion Complexes with PLGA-PEG-PLGA Triblock Copolymers as Drug Delivery Systems.” AAPS PharmSciTech 15, no. 1 (2014): 177-188. http://link.springer.com/article/10.1208/s12249-013-0051-1

“Abstract: Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEG-PLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined.”