Tuesday, November 23, 2021

mPEG-PLGA from PolySciTech used in research on the effect of LA:GA Sequencing


During the normal ring-opening polymerization of PLGA, the glycolide monomer typically reacts faster and more readily than the lactide monomer leading to non-random distribution of monomers along the polymer chain. This process competes with transesterification and other reactive processes in polymer manufacturing which act to improve randomness along the chain. Recently, researchers at Purdue University developed a novel method to make small quantities of mPEG-PLGA with precisely controlled monomer distribution. They used mPEG-PLGA (Cat# AK010) from PolySciTech (www.polyscitech.com) (manufactured using conventional bulk-melt ring-opening polymerization) to compare the various batches they had made. In addition to traditional PLGA offerings, Akina has recently begun adding products of PLGA alternating LA:GA based on 3-methylglycolide monomer (e.g. cat# AP279 – AP281). This research holds promise to provide a more mechanistic understanding of PLGA sequencing effect on the polymer properties. Read more: Yoo, Jin, Dhushyanth Viswanath, and You-Yeon Won. "Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties." ACS Macro Letters 10 (2021): 1510-1516. https://pubs.acs.org/doi/abs/10.1021/acsmacrolett.1c00637

“Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic-co-glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled “uniform PLGA” polymers through control of the rate of comonomer addition. Using this method, a series of PEG–PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol–gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.”

Tuesday, November 16, 2021

PLGA-PEG-COOH from PolySciTech used in development of carborane-loaded nanoparticles for prostate cancer treatment

PSMA is a marker which is overexpressed on cancer cells and can provide an attractive target for ligand-based therapies. Recently researchers at University of California San Francisco used PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create PSMA-targetting nanoparticles loaded with carborane for boron neutron capture therapy against prostate cancer. This research holds promise to improve therapeutic options for cancer. Read more: Meher, Niranjan, Kyounghee Seo, Sinan Wang, Anil P. Bidkar, Miko Fogarty, Suchi Dhrona, Xiao Huang et al. "Synthesis and Preliminary Biological Assessment of Carborane-Loaded Theranostic Nanoparticles to Target Prostate-Specific Membrane Antigen." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c16383

“Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA-b-PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [89Zr]DFB(25) NPs and [89Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(−) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo. In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA-b-PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo.”

PLGA-NH2 from PolySciTech used in testing nanoparticles for platinum-based anticancer therapy


Cisplatin is the first FDA approved metal-based drug for treatment of solid tumors as it uses platinum as an active agent. In the blood stream, however, it reacts with glutathione which diminishes its effectiveness. Recently, researchers at City University of New York used PLGA-NH2 (AI010) to make Cy5.5 labeled nanoparticles for tracking purposes as part of their research in making nanoparticles for delivery of cisplatin. This research holds promise for improving treatments against cancer. Read more: Marek T. Wlodarczyk “Enhanced Platinum (II) Drug Delivery for Anti-cancer Therapy” PhD Dissertation City University of New York, 2021 https://academicworks.cuny.edu/cgi/viewcontent.cgi?article=5668&context=gc_etds

“Over the years, anti-cancer therapies have improved the overall survival rate of patients. Nevertheless, the traditional free drug therapies still suffer from side effects and systemic toxicity, resulting in low drug dosages in the clinic. This often leads to suboptimal drug concentrations reaching cancer cells, contributing to treatment failure and drug resistance. Among available anticancer therapies, metallodrugs are of great interest. Platinum (II)-based agents are highly potent and are used to treat many cancers, including ovarian cancer (OC). Cisplatin (cisdiaminedichloroplatinum (II)) is the first Food and Drug Administration (FDA)-approved metallodrug for treatment of solid tumors, and its mechanism of action is based on inhibition of cancer cell replication via binding to nuclear DNA. However, circulating cisplatin binds to glutathione and other proteins in the blood compartment, diminishing the concentration of the free drug available for therapy. Also, highly potent cisplatin is associated with severe side effects, limiting the dosage of Pt(II) that can be administered in the clinic. The next generation Pt(II) drugs aim at sustaining the same effectiveness while improving systemic toxicity. Carboplatin is a second-generation Pt-based agent approved by the Food and Drug Administration (FDA). Slower hydrolysis times for carboxylate ligands in carboplatin, compared to rather fast times for chlorine ligands in cisplatin, lead to longer blood circulation times and lesser side effects. The therapeutic effect of carboplatin is comparable with cisplatin in some tumors, but it requires higher drug dosages, and the survival rate did not improve.”

Thursday, October 28, 2021

PLGA from PolySciTech used in development of technetium-loaded nanoparticles for theranostic applications


The primary benefit and complication of nanoparticles is that they are small. The same diminutive size which allows them to flow freely through the circulatory system also makes their detection and localization difficult. Recently, researchers at University of Rome (Italy) used PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create technetium-labelled nanoparticles. These radio-labelled nanoparticles enabled discrete and accurate imaging of the localization of particles in an animal model. This research holds promise to improve nanobased therapies against several disease states including cancer. Read More: Varani, Michela, Giuseppe Campagna, Valeria Bentivoglio, Matteo Serafinelli, Maria Luisa Martini, Filippo Galli, and Alberto Signore. "Synthesis and Biodistribution of 99mTc-Labeled PLGA Nanoparticles by Microfluidic Technique." Pharmaceutics 13, no. 11 (2021): 1769. https://www.mdpi.com/1999-4923/13/11/1769

“The aim of present study was to develop radiolabeled NPs to overcome the limitations of fluorescence with theranostic potential. Synthesis of PLGA-NPs loaded with technetium-99m was based on a Dean-Vortex-Bifurcation Mixer (DVBM) using an innovative microfluidic technique with high batch-to-batch reproducibility and tailored-made size of NPs. Eighteen different formulations were tested and characterized for particle size, zeta potential, polydispersity index, labeling efficiency, and in vitro stability. Overall, physical characterization by dynamic light scattering (DLS) showed an increase in particle size after radiolabeling probably due to the incorporation of the isotope into the PLGA-NPs shell. NPs of 60 nm (obtained by 5:1 PVA:PLGA ratio and 15 mL/min TFR with 99mTc included in PVA) had high labeling efficiency (94.20 ± 5.83%) and > 80% stability after 24 h and showed optimal biodistribution in BALB/c mice. In conclusion, we confirmed the possibility of radiolabeling NPs with 99mTc using the microfluidics and provide best formulation for tumor targeting studies. Keywords: radiolabeled nanoparticles; poly (lactic-co-glycolic acid) (PLGA); nuclear medicine; microfluidics”

PLGA from PolySciTech used in research on 3D printed graphene based on a temporary nickel scaffold


Typically, the biodegradability of PLGA is utilized in a medical sense to create structures which slowly break down over time in the human body in a non-toxic manner for tissue engineering or drug-delivery applications. PLGA’s degradation, however, is hydrolysis and occurs in general upon contact with any water proceeding faster in acid or alkali conditions. This allows PLGA to be used in engineering applications as a temporary structure. Recently, researchers at University of Cincinnati and A&T North Carolina State University used PLGA (PolyVivo cat# AP234) from PolySciTech (www.polyscitech.com) as a temporary binder for nickel particles as part of development of a novel 3D-printed catalyst system for graphene structure creation. This research holds promise to improve capabilities of forming complex structures from reinforced materials. Read more: Kondapalli, Vamsi Krishna Reddy, Xingyu He, Mahnoosh Khosravifar, Safa Khodabakhsh, Boyce Collins, Sergey Yarmolenko, Ashley Paz y Puente, and Vesselin Shanov. "CVD Synthesis of 3D-Shaped 3D Graphene Using a 3D-Printed Nickel–PLGA Catalyst Precursor." ACS Omega (2021). https://pubs.acs.org/doi/abs/10.1021/acsomega.1c04072

“Earlier, various attempts to develop graphene structures using chemical and nonchemical routes were reported. Being efficient, scalable, and repeatable, 3D printing of graphene-based polymer inks and aerogels seems attractive; however, the produced structures highly rely on a binder or an ice support to stay intact. The presence of a binder or graphene oxide hinders the translation of the excellent graphene properties to the 3D structure. In this communication, we report our efforts to synthesize a 3D-shaped 3D graphene (3D2G) with good quality, desirable shape, and structure control by combining 3D printing with the atmospheric pressure chemical vapor deposition (CVD) process. Direct ink writing has been used in this work as a 3D-printing technique to print nickel powder–PLGA slurry into various shapes. The latter has been employed as a catalyst for graphene growth via CVD. Porous 3D2G with high purity was obtained after etching out the nickel substrate. The conducted micro CT and 2D Raman study of pristine 3D2G revealed important features of this new material. The interconnected porous nature of the obtained 3D2G combined with its good electrical conductivity (about 17 S/cm) and promising electrochemical properties invites applications for energy storage electrodes, where fast electron transfer and intimate contact with the active material and with the electrolyte are critically important. By changing the printing design, one can manipulate the electrical, electrochemical, and mechanical properties, including the structural porosity, without any requirement for additional doping or chemical postprocessing. The obtained binder-free 3D2G showed a very good thermal stability, tested by thermo-gravimetric analysis in air up to 500 °C. This work brings together two advanced manufacturing approaches, CVD and 3D printing, thus enabling the synthesis of high-quality, binder-free 3D2G structures with a tailored design that appeared to be suitable for multiple applications.”

Monday, October 25, 2021

PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy


PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy

Galbanic acid (compound extracted from Asafoetida herb) has demonstrated apoptotic activity against cancer cells in the past. Recently, researchers at Mashhad University of Medical Sciences utilized PEG-PLA (PolyVivo cat# AK054) to create galbanic acid-loaded nanoparticles. They tested these for efficacy and safety both in-vitro as well as in an in-vivo model. This research may provide for improved treatments of colon cancer in the future. Read more: Hashemi, Maryam, Maryam Afsharzadeh, Maryam Babaei, Mahboubeh Ebrahimian, Khalil Abnous, and Mohammad Ramezani. "Enhanced anticancer efficacy of docetaxel through galbanic acid encapsulated into PLA-PEG nanoparticles in treatment of colon cancer, in vitro and in vivo study." Journal of Bioactive and Compatible Polymers (2021): 08839115211053922. https://journals.sagepub.com/doi/abs/10.1177/08839115211053922

“Abstract: Cancer is one of the most leading causes of human mortality and despite outstanding breakthrough in introducing new therapeutic approaches, the clinical outcomes are disappointing. Therefore, extensive research in design and preparation of more efficient drug delivery systems can open a window to shine light into the therapeutic modality. In this study, we evaluated the effect of galbanic acid (GBA) encapsulated into PLA-PEG nanoparticles (NPs) to enhanced anticancer efficacy of docetaxel (DOC) for the treatment of colon cancer. Prepared NPs were characterized by different methods in terms of size, zeta potential, and drug loading capacity. MTT assay was used to investigate the anti-proliferation of GBA-loaded PEG-PLA NPs along with DOC. The therapeutic efficacy of PEG-PLA@GBA NPs & DOC was further investigated in C26 tumor-bearing BALB/c mice model. The resulting NPs were narrowly distributed (PDI = 0.06) with the mean diameter of 148 ± 9 nm with somewhat negative charge. GBA were efficiently loaded into mPEG-PLA NPs with encapsulation efficiency of about 40% ± 3. Cytotoxicity studies showed that NPs loaded with GBA and fixed concentration of docetaxel (20 nM) have higher toxicity (IC50 = 6 ± 1.8 µM) than either PEG-PLA@GBA (IC50 = 8 ± 1.2 µM) or free GBA (IC50 = 15 ± 3.5 µM) in C26 cells. In vivo studies revealed a synergistic effect of PEG-PLA@GBA NPs and DOC on tumor growth inhibition and survival rate in comparison with monotherapy approach. Keywords: Galbanic acid, docetaxel, PEG-PLA nanoparticles, colon cancer, combination therapy”

Tuesday, October 5, 2021

PLGA from PolySciTech used in development of microelectrode array for non-opioid pain management


Current pain management strategies typically rely on opioid medications which have a high propensity to lead to addiction. Opioid addiction has become a world-wide societal problem in recent years requiring research into opioid-free pain relief strategies. Recently, researchers at University of Washington used mPEG-PLGA (Cat# AK106) and PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create curcumin-loaded nanoparticles as part of development of nanoparticle loaded microelectrode array for pain management. This research holds promise to improve pain management strategies in the future. Read more: Xu, Nuo. "Nanoparticle loaded implantable flexible microelectrode arrays for pain management after spinal cord surgery." PhD diss., University of Washington, 2021. https://search.proquest.com/openview/530e9f32e470658b868b55aabf7b6312/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract: The health care system currently faces significant burden with abuse of opioids and an unmet market need for pain management after surgery and injury. A drug delivery device that can improve drug delivery efficiency, increase drug duration of action, and deliver anesthetics topically with low toxicity is needed. Implantable flexible microelectrode arrays are widely used after spinal cord injury for pain mainagement, but they have limitations in improving the solubility, bioavailability, and permeability of drug. Biodegradable polymeric nanoparticles have highly tailorable physicochemical properties, and with incorporation on microelectrode arrays (MEAs), may increase the physical and chemical properties of therapeutic agents such as permeability, solubility and bioavailability. However, drug-loaded biodegradable nanoparticle-polypyrrole coated MEA for drug delivery has not been reported in literature. Therefore, we investigate the use of biodegradable nanoparticles for controlled release of bupivacaine hydrochloride from MAEs for pain management following spinal cord surgery. Bupivacaine hydrochloride, a commonly used FDA-approved anesthetic, is chosen as the model drug due to its nerve block and anti-inflammatory effects. This work starts with the exploration of the relationship between the formulation parameters of biodegradable nanoparticles and their physicochemical properties. Then, the bupivacaine hydrochloride loaded nanoparticles are formulated, and the drug loading of the nanoparticles is explored through iterating formulation parameters. Thereafter, nanoparticles with different surface charges are loaded on the MAEs to determine the relationship between the surface charge of nanoparticles and the release behavior of these nanoparticles. Finally, the release behavior of the nanoparticles from the MAEs is used as a guide to further optimize the bupivacaine hydrochloride loaded nanoparticle formulation.”