Monthly Archives: September 2015

New Activated PEGs available from PolySciTech

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable, biocompatible and speciality polymers for research applications. Recently five new activated PEG products have been added. These include: AE016 Azide-Poly(ethylene glycol)-Trimellitic anhydride (3000Da), AE017 Butoxy-Poly(ethylene glycol)-Azide (3000 Da), AE018 Azide-Poly(ethylene glycol)-Amine (5000 Da), AE019 Azide-Poly(ethylene glycol)-Thiol (6000 Da), and AE020 Butoxy-Poly(ethylene glycol)-Amine (3000 Da). These PEGs can be used for a wide array of conjugation reactions, ‘Click’ chemistry, and other applications. See all activated PEG products here https://akinainc.com/polyscitech/products/polyvivo/sequential.php#PEGs

PLGA-PEG-PLGA thermogel mechanism and molecular weight effects detailed

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA polymers with varying molecular weights and block constituents (PolyVivo AK012, AK024, AK097, etc.). Unlike normal materials, these polymers when dissolved in aqueous solution for a liquid at cold temperature and solidify when the temperature is increased. The primary mechanism for this lies in the competing forces between water-molecule binding attraction to the PEG block and entropic forces encouraging water to be free of the PEG block. Recently a paper was published detailing the effects of polymer block sizes, concentration, and temperature on the gelation and precipitation behavior of these types of polymers. Read more: Chen, Liang, Tianyuan Ci, Lin Yu, and Jiandong Ding. “Effects of Molecular Weight and Its Distribution of PEG Block on Micellization and Thermogellability of PLGA–PEG–PLGA Copolymer Aqueous Solutions.” Macromolecules (2015). http://pubs.acs.org/doi/abs/10.1021/acs.macromol.5b00168

“Abstract: While amphiphilic block copolymers have been extensively investigated, little is known about the effect of molecular weight distribution (MWD) of the hydrophilic blocks on corresponding physical gelation behaviors. Herein, we employed thermogelling poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA–PEG–PLGA) as the model system. We synthesized the block copolymer and prepared a series of copolymers with similar PLGA blocks but varied lengths and distributions of the PEG block. The micellization in dilute solutions was detected by light scattering and fluorescence spectroscopy using the probe 1-anilino-8-naphthalenesulfonate (ANS) specifically for the micelle coronae. Vial-inverting observations and rheological measurements were carried out to judge sol or gel states for the concentrated aqueous systems. The gel-to-sol transition or sol-to-gel transition occurred only with appropriate molecular weight (MW) and molar mass dispersity (ĐM). In this study, we denote the normal hydrogel with a sol-to-gel transition upon cooling as gel-1, and gel-2 refers to the thermogel with a reversed physical gelation in a sol-to-gel transition upon heating. We found that wider MWD of PEG block sometimes even led to coexistence of normal gel (gel-1) and reversed gel (gel-2). The corresponding concentrated aqueous system of copolymers underwent gel-1-to-sol-to-gel-2 transitions with an increase of temperature. The macroscopic physical gelation was further discussed based upon the mesoscopic micellization and the micellar aggregation.”

Post-reaction DMSO removal/purification Tips and Techniques

Since many of the products sold by PolySciTech Division of Akina, Inc. (www.polyscitech.com) are used in reactions, I often receive questions about their usage and subsequent purification techniques. One common solvent for performing conjugations and other reactions in is dimethylsulfoxide (DMSO). This solvent is a highly versatile polar aprotic solvent with low toxicity. It has some drawbacks however in that its boiling point is extremely high (189 °C) and it has very bad miscibility with typical non-solvents used for polymer purification such as hexane or diethyl ether. Attempts at ‘precipitating’ a PLGA based conjugate material from DMSO into one of these non-solvents typically result in the formation of two separate layers and minimal DMSO removal. We have used this solvent at Akina for a variety of applications and have two methods which are used for DMSO removal both of which have pros and cons:

  1. Rotovap: with deep vacuum and heat about 50 C. For this one deep vacuum is important and typical peristaltic vacuums or aspirators are insufficient. My personal favorite for this one is the Welch Duoseal type vacuum because of its robustness but it can also be accomplished using a direct-drive type vacuum or other capable of dropping the pressure very low (mTorr range). After rotovap, to purify redissolve in either dichloromethane (DCM) or another more convienent solvent with low boiling point and precipitate in a traditional non-solvent such as hexane or diethyl ether. The pro’s to this method are that it’s effective, fast, and simple with no additional solvents/chemicals added. The con of this method is heat. Heat exposure won’t damage the polyester under deep vacuum, but if you have something delicate attached (peptide, protein, etc.) then it could be damaged by heating.
  2. Dialysis: Dialyze against deionized water. Since DMSO is water soluble it will go into the deionized water easily. Subsequently this can be dialyzed against acetone to replace the water with acetone. If doing dialysis make sure to use a MWCO membrane lower than the molecular weight of the polymer. To prevent premature degradation it is best to dialyze in refrigerator (4C) and not for extensive periods of time (no more than 1-2 days). Afterwards rotovap away the much more volatile solvent at room temperature or precipitate in a non-solvent. The pro to this method is no heating is involved. The con to it is that it is a slow process with lots of water exposure.

 

These are just two methods but there are many ways to remove DMSO. Keep in mind all the parameters of your particular research prior to deciding the best method to desolvate your system.

mPEG-PLGA used for codelivery of SH-Aspirin and curcumin as a treatment of ovarian cancer

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including mPEG-PLGA. This polymer has a water-soluble side (mPEG) and an oil-soluble side (PLGA). Because of this, it tends to self-assemble into micelles or particles that disperse in water and contain oil-soluble compounds in the interior core. Typically administering such compounds to a patient is very difficult because they cannot be dissolved in isotonic saline for injection and they tend to be removed rapidly from the blood stream by the kidneys and liver. Dispersing these hydrophobic medicinal compounds inside the polymer core allows them to have longer circulation times and higher therapeutic effect. Recently research has shown that mPEG-PLGA can assist in the codelivery of SH-aspirin and curcumin to improve their therapeutic efficacy against ovarian cancer. Read more: Zhou, Lin, Xingmei Duan, Shi Zeng, Ke Men, Xueyan Zhang, Li Yang, and Xiang Li. “Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis.” International journal of nanomedicine 10 (2015): 5205. Full-Text available from NIH: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547632/

“Abstract: Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. Keywords: drug delivery, cancer therapy, ovarian cancer, synergistic effect”

PolySciTech PLGA-PEG-PLGA used for antibiotic delivery system in craniofacial reconstruction

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide variety of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA block copolymers. These polymers have a unique blend of hydrophilic and hydrophobic components such that they dissolve into cold water but form into a solid gel when the water is heated to body temperature. Recently researchers at Rice University and Albany medical center utilized PolySciTech PLGA-PEG-PLGA thermogels (Cat# AK012 and AK024) to load antibiotics into porous PMMA scaffold and control their release rate so as to generate a spacer that prevents bacterial infection as the patient heals post-surgery. Read more: Mountziaris, P. M., S. R. Shah, J. Lam, G. N. Bennett, and A. G. Mikos. “A rapid, flexible method for incorporating controlled antibiotic release into porous polymethylmethacrylate space maintainers for craniofacial reconstruction.” Biomaterials science (2015). http://pubs.rsc.org/en/content/articlehtml/2015/bm/c5bm00175g

 

“Abstract: Severe injuries in the craniofacial complex, resulting from trauma or pathology, present several challenges to functional and aesthetic reconstruction. The anatomy and position of the craniofacial region make it vulnerable to injury and subsequent local infection due to external bacteria as well as those from neighbouring structures like the sinuses, nasal passages, and mouth. Porous polymethylmethacrylate (PMMA) “space maintainers” have proven useful in staged craniofacial reconstruction by promoting healing of overlying soft tissue prior to reconstruction of craniofacial bones. We describe herein a method by which the porosity of a prefabricated porous PMMA space maintainer, generated by porogen leaching, can be loaded with a thermogelling copolymer-based drug delivery system. Porogen leaching, space maintainer prewetting, and thermogel loading all significantly affected the loading of a model antibiotic, colistin. Weeks-long release of antibiotic at clinically relevant levels was achieved with several formulations. In vitro assays confirmed that the released colistin maintained its antibiotic activity against several bacterial targets. Our results suggest that this method is a valuable tool in the development of novel therapeutic approaches for the treatment of severe complex, infected craniofacial injuries.”

 

Article from PolySciTech regarding polymer analysis

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers and related block copolymers. In addition to this, contract analysis is also offered for a variety of polymer-based and other samples. Recently our group has published a paper detailing methodology of polymer analysis post-formulation in parental products. Read more: Garner, John, Sarah Skidmore, Haesun Park, Kinam Park, Stephanie Choi, and Yan Wang. “A Protocol for Assay of Poly (lactide-co-glycolide) in Clinical Products.” International Journal of Pharmaceutics (2015). http://www.sciencedirect.com/science/article/pii/S0378517315301605

“Abstract: Poly(lactide-co-glycolide) (PLGA) is the key component of long acting drug products responsible for providing sustained release in a controlled manner. The objective of the current study was to develop and validate an analytical protocol to determine key properties of PLGA used in commercial long-acting drug products. Procedures to isolate PLGA from commercial products have been established and the key properties of PLGA, such as polymer molecular weight, lactide:glycolide (L:G) ratio, and nature of polymer end-cap, have been determined. Identification of the polymer end-cap was confirmed by using two PLGA polymers with acid and ester end-caps. Trelstar® and Risperdal Consta® were chosen as model products. The calculated L:G ratios of PLGA used in Trelstar® and Risperdal® are 52:48 and 78:22, respectively. PLGAs from both Trelstar® and Risperdal Consta® possess ester end-caps. Since the properties of specific PLGA in clinically used formulations are not readily available, this protocol will be useful in developing PLGA-based long acting drug products.”