Monthly Archives: May 2015

PolySciTech PLGA used for development of nanofiber diameter measurement tool

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including poly(lactide-co-glycolide).  Recently PolySciTech PLGA (AP082) was dissolved 25% w/v in hexafluoroisopropanol and electrospun through a 25Ga needle to form reference fibers used in the development of a nanofiber measurement tool. Read more: Hotaling, Nathan A., Kapil Bharti, Haydn Kriel, and Carl G. Simon. “DiameterJ: A Validated Open Source Nanofiber Diameter Measurement Tool.” Biomaterials (2015). http://www.sciencedirect.com/science/article/pii/S0142961215004652

“Abstract: Despite the growing use of nanofiber scaffolds for tissue engineering applications, there is not a validated, readily available, free solution for rapid, automated analysis of nanofiber diameter from scanning electron microscope (SEM) micrographs. Thus, the goal of this study was to create a user friendly ImageJ/FIJI plugin that would analyze SEM micrographs of nanofibers to determine nanofiber diameter on a desktop computer within 60 seconds. Additional design goals included 1) compatibility with a variety of existing segmentation algorithms, and 2) an open source code to enable further improvement of the plugin. Using existing algorithms for centerline determination, Euclidean distance transforms and a novel pixel transformation technique, a plugin called “DiameterJ” was created for ImageJ/FIJI. The plugin was validated using 1) digital synthetic images of white lines on a black background and 2) SEM images of nominally monodispersed steel wires of known diameters. DiameterJ analyzed SEM micrographs in 20 seconds, produced diameters not statistically different from known values, was over 10-times closer to known diameter values than other open source software, provided hundreds of times the sampling of manual measurement, and was hundreds of times faster than manual assessment of nanofiber diameter. DiameterJ enables users to rapidly and thoroughly determine the structural features of nanofiber scaffolds and could potentially allow new insights to be formed into fiber diameter distribution and cell response. Keywords: ImageJ; image analysis; FIJI; scaffold; morphology; structure”

PLGA-PEG-PLGA used for simvastatin delivery thermogel

PolySciTech (www.polyscitech.com) provides a wide array of PLGA-PEG-PLGA thermogel polymers used for a wide variety of research applications. Recently, researchers have utilized PLGA-PEG-PLGA thermogels for delivery of simvastatin for bone tissue regeneration. Read more: Yan, Qi, Li‐Qun Xiao, Lei Tan, Wei Sun, Tao Wu, Liang‐Wen Chen, Yan Mei, and Bin Shi. “Controlled release of simvastatin‐loaded thermo‐sensitive PLGA‐PEG‐PLGA hydrogel for bone tissue regeneration: In vitro and in vivo characteristics.” Journal of Biomedical Materials Research Part A (2015). http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.35499/abstract

“Abstract: Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation were analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing. Keywords: PLGA-PEG-PLGA;simvastatin;drug delivery;thermo-sensitive;bone”

PolySciTech PLGA used for development of episcleral drug delivery

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers. Recently, a PLGA 85:15 (cat# AP087) was utilized by University of Cincinnati as part of their research for development of an adhesive ocular drug release system. Read more: Wen, He, and S. Kevin Li. “Characterization of silicone pressure-sensitive adhesive episcleral implant for drug delivery.” Drug Development and Industrial Pharmacy 0 (2015): 1-9. http://informahealthcare.com/doi/abs/10.3109/03639045.2015.1035280

“Abstract: The development of an effective sustained ocular drug delivery system remains a challenging task. The objective of the present study was to characterize a silicone pressure sensitive adhesive (PSA) episcleral implant system for transscleral drug delivery. Silicone PSA implants for dexamethasone, atenolol, and bovine serum albumin (BSA) were prepared at different polymer-to-drug mass ratios. Implant adhesion to human cadaver sclera was measured. Drug release experiments were conducted in well-stirred containers in vitro. The results were then analyzed using a pharmacokinetic model and in vitro–in vivo data comparison from previous studies. The silicone PSA episcleral implants in the present study had an average diameter of 3.5 mm and a thickness of 0.8 mm. Drug release from the silicone PSA implants was influenced by drug solubility, implant polymer content, and implant coating. Drug release from the implants was observed to follow the receding boundary release mechanism and was solubility dependent with the higher water solubility drug showing higher release rate than the low-solubility drug. Increasing polymer content in the implants led to a significant decrease in the drug release rate. Coated implants reduced the initial burst effect and provided lower release rates than the uncoated implants. These implants provided sustained drug release that could last up to several months in vitro and demonstrated the potential to offer drug delivery for chronic ocular diseases via the transscleral route. Keywords: Controlled release, episcleral implant, macromolecules, silicone adhesive, transscleral delivery”

Solubility of PLLA type polymers

PolySciTech (www.polyscitech.com) provides a wide array of polymers of many different types. Often I receive questions about why PLLA and related PEG-PLLA lacks solubility in some organic solvents such as acetone or THF. This is due to chirality. The PLLA type polymers have relatively poor solubility in solvents such as THF and acetone because the PLLA polymer chains pack into crystaline domains that THF can not dissolve well. They do have good solubility in other solvents such as DCM. Conversely, P(DL)La type polymers have good solubility in acetone and THF as well as DCM. PST has a handy solubility chart for polymers here (http://akinainc.com/pdf/Polymer%20Solubility%2040624.pdf)

Technical Note: AK097 Dissolution

PolySciTech (www.polyscitech.com) provides a wide array of PLGA-PEG-PLGA thermogels. Several of these thermogels (AK12 and AK24) have optimal dissolution in cold water (5-10C) due to a low LCST of about 20C. Recently, in-house testing has shown that PLGA-PEG-PLGA thermogels which have a higher LCST ~30C such as AK97 and some others dissolve best at room temperature and dissolve very slowly to not at all when in cold condition. For the use of AK097 thermogels in your lab dissolve at room temperature for a few days prior to injecting. For use of AK12/AK24 type thermogels dissolve in cold condition (5-10C).

mPEG-PLGA used as part of nanogel intraocular drug delivery system

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable block copolymers including mPEG-PLGA. Recently these types of polymers were used as a precursor for a 2,2-bis(2-oxazoline) crosslinked nanogel designed for ocular delivery of bevacizumab. Read more: Hu, Chao-Chien, Jen-Ray Chaw, Yu-Chih Chen, Chin-Fu Chen, and Hsia-Wei Liu. “A Novel Thermo-Responsive Nanogel for Intraocular Drug Delivery.” Journal of Computational and Theoretical Nanoscience 12, no. 5 (2015): 762-768. http://www.ingentaconnect.com/content/asp/jctn/2015/00000012/00000005/art00012

“Abstract: The novel amphiphilic hydrophilic–hydrophobic block copolymers of methoxy-poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (mPEG-PLGA) were synthesized by the ring-opening polymerization, cross-linked with 2,2-bis(2-oxazoline) (BOX) and the chemical structures were characterized by 1H nuclear magnetic resonance (1H-NMR). Cross-linked mPEG-PLGA-BOX block copolymers formed a core–shell micellar structure with a critical micelle concentration of 9.21 × 10–4 mg/mL. The mPEG-PLGA-BOX micelles were spherical with a hydrodynamic diameter of between 26.10 nm to 39.70 nm. A solution containing mPEG-PLGA-BOX micelles exhibited a fast and reversible sol–gel phase transition behavior that could convert into nanogels at body temperature. The pharmacokinetic release rate of anti-vascular endothelial growth factor (VEGF) entrapped in nanogels were examined in vitro. Release profiles of the anti-VEGF agents (bevacizumab) showed that there was sustained release for approximately 30 days. Released bevacizumab inhibited the RF6A cells growth, which showed drug delivery system may provide localized and sustained release of bevacizumab over an extended period. The mPEG-PLGA-BOX nanogel has been successfully synthesized and determined as thermosensitive and biocompatible. This suggests that the nanogel may be considered as a novel biomaterial with potential as the form of injectable dilute dispersions or as in situ gelling carrier for extended anti-VEGF drug release to treat intraocular neovascular diseases.”

Folic acid targeted PLGA-PEG polymer used for chemotherapeutic curcumin delivery

PolySciTech (www.polyscitech.com) provides a wide array of PLGA-PEG block copolymers. Included with this are various activated polymers useful for generating PLGA-PEG-folate conjugates. Recently these kinds of polymers were used for nanoparticle delivery of chemotherapeutic curcumin. Read more: Pillai, Jisha J., Arun Kumar T. Thulasidasan, Ruby John Anto, Nandan C. Devika, N. Ashwanikumar, and GS Vinod Kumar. “Curcumin entrapped folic acid conjugated PLGA–PEG nanoparticles exhibit enhanced anticancer activity by site specific delivery.” RSC Advances 5, no. 32 (2015): 25518-25524. http://pubs.rsc.org/en/content/articlehtml/2015/ra/c5ra00018a

 

“Abstract: Herein we report curcumin entrapped nanoparticles of PLGA–PEG copolymer which were conjugated with folic acid (PPF copolymer) for site specific targeting since many cancer cells exhibit external folic acid binding receptors. The PPF copolymer was synthesised by two steps using DCC/NHS chemistry and characterized by FT-IR and 1H-NMR techniques. The curcumin was encapsulated in PPF by single emulsion-solvent evaporation method. The nanoparticles were characterised by TEM and DLS for their size and morphology. The thermal properties were assessed by DSC data. In vitro release kinetics measurements of the drug from the nanoparticles showed a controlled release pattern over a period of time. The MTT assay depicted a high amount of cytotoxicity of PPF nanocurcumin in HeLa cells. Cellular uptake studies demonstrated the efficacy of surface engineering with folate over free nanoparticles. Furthermore, the biological evaluations, for example AO/EB staining, DAPI staining, and clonogenic assay of the nanoparticles confirm the efficacy and mechanism by which the cytotoxicity was induced.”

Pillai, 2015 PLGA-PEG-Folate