Tuesday, December 3, 2019

PLGA from PolySciTech Used in Research on Nanoparticle Generation Methods

There are many methods to generate nanoparticles and they all vary based on the quality of the particles as well as the scalability and control of the method. Recently, researchers at American University of Sharjah (United Arab Emirates) used PLGA (AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles according to several novel microfluidic and electrical methods. They recently published about these methods in a series of manuscripts and presentations. Read more:

Abualsayed, Alsaeed M., Sara A. Abouelmagd, and Mohamed Abdelgawad. "Miniaturised preparation of polymeric nanoparticles using droplet manipulation on open surfaces." Micro & Nano Letters 14, no. 13 (2019): 1312-1316. (https://digital-library.theiet.org/content/journals/10.1049/mnl.2019.0421) “Abstract: A digital microfluidics platform for the preparation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) was developed. Droplets of PLGA in dimethylformamide were merged with droplets of deionised water by electrical actuation on a digital microfluidics device to form PLGA NPs through nanoprecipitation. The developed platform is automated and allows for the preparation of polymeric NPs with small size and high uniformity. Using the platform, the authors were able to prepare monodisperse PLGA NPs as small as 115 nm with a polydispersity index (PDI) of 0.14 which can be challenging with conventional preparation techniques on the macroscale. Size of the prepared NPs can be tuned through proper choice of the volume ratio between the two merged droplets which controls the induced internal convection flow after merging. Concentration of PLGA in the dimethylformamide droplet also had an effect on the size and polydispersity of the formed NPs. These results prove the potential use of digital microfluidics for testing combinatorial synthesis of different polymeric NPs for various applications. This approach allows robust and automated screening of NP preparations using only few microlitres of the reagents used, thus conserving precious and costly NP components and loaded therapeutic agents.”

Abualsayed, Alsaeed, Sara Abouelmagd, and Mohamed Abdelgawad. "Nanoparticles synthesis using digital microfluidics." In 2019 IEEE 14th International Conference on Nano/Micro Engineered and Molecular Systems (NEMS), pp. 201-204. IEEE, 2019. (https://ieeexplore.ieee.org/abstract/document/8915616/) “Abstract: We developed a Digital Microfluidics platform for synthesis of Poly(Lactic-co-glycolic) acid (PLGA) Nanoparticles (NPs). As far as we know, it is the first time droplet manipulation on open surfaces is used in NP synthesis. The platform we developed is automated and allows for synthesis of polymeric NPs with smaller size and higher uniformity. Using our platform, we were able to prepare monodisperse PLGA NPs as small as 115 nm with a polydispersity index (PDI) of 0.14 which can be challenging with conventional preparation techniques on the macroscale. Size of the prepared NPs was found to decrease with increasing the volume ratio between the water droplet and the dimethylformamide-PLGA droplet merged on the device. Increasing the concentration of PLGA resulted in larger particle size and smaller PDI. We believe our results prove the potential use of digital microfluidics for testing combinatorial synthesis of different polymeric NPs for various applications.”

PLGA-PEG-PLGA Thermogel from PolySciTech Used in Development of Spinal Cord Injury Treatment

Traumatic injuries to the spinal column typically occur due to trauma (vehicular/sports accident) which damages or severs the nerves in the spine. Since neural tissue does not repair itself the same way as other tissues, many of these injuries result in a lifetime of paralysis. Recently, researchers at New York University School of Medicine and Qingdao University (China) used PLGA-PEG-PLGA thermogel (AK097) from PolySciTech (www.polyscitech.com) to create a Atsttrin (a progranulin (PGRN) derivative) delivery gel for treatment of spinal cord injury. This research holds promise to repair neural damage and may potentially be used as part of treatment for injury induced paralysis. Read more: Wang, Chao, Lu Zhang, Jean De La Croix Ndong, Aubryanna Hettinghouse, Guodong Sun, Changhong Chen, Chen Zhang, Ronghan Liu, and Chuan-ju Liu. "Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice." Journal of Neuroinflammation 16, no. 1 (2019): 1-12. https://link.springer.com/article/10.1186/s12974-019-1630-1

“Abstract: Purpose: Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI. Methods: PGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins. Results: After SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury. Grn−/− mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated that Grn−/− mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency. Conclusion: PGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury. Keywords: Progranulin Inflammation Apoptosis Spinal cord injury”

Friday, November 22, 2019

PLGA-PEG-PLGA Thermogelling polymers from PolySciTech used In Development of Hyaluronic Acid Delivery System.

Block copolymers can be used to develop thermogelling systems which are liquid at cold temperatures and turn solid when the temperature increases. One practical application of this phenomenon is drug delivery in which a cold solution of the polymer and a drug are injected into a patient and then the polymer solidifies around the drug upon heating to the patient’s body temperature (37C/98.6F) to delay and control its release rate. Recently, researchers at Rowan University used several PLGA-PEG-PLGA polymers (AK097, AK088, AK085, AK091, etc.) from PolySciTech (www.polyscitech.com) to develop a thermogelling system for the ocular delivery of hyaluronic acid. This research holds promise for the development of thermogelling drug-delivery systems. Read more: Osorno, Laura L., Daniel E. Maldonado, Ricky J. Whitener, Alyssa N. Brandley, Alex Yiantsos, Jamie DR Medina, and Mark E. Byrne. "Amphiphilic PLGA‐PEG‐PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid." Journal of Applied Polymer Science (2019). https://onlinelibrary.wiley.com/doi/abs/10.1002/app.48678

“ABSTRACT: Different compositional parameters of poly(D,L‐lactic‐co‐glycolic acid)‐b‐poly(ethylene glycol) triblock copolymers (PLGA‐PEG) were varied to analyze their effect on gel formation and mechanical properties. Parameters such as hydrophilic/hydrophobic ratio (PLGA/PEG ratio), lactic acid/glycolic acid ratio (LA/GA ratio), PEG molecular weight (PEG Mw), polymer solution concentration, copolymer molecular weight (Mw), and polydispersity index (PDI) were studied in this work. For copolymers with PEG Mw of 1500 Da, gelation temperature (34–37 °C) was affected by D,L‐LA/GA ratio and Mw; while modulus was affected by LA/GA ratio, Mw, and Mn. Based on the parametric study, an injectable, thermoresponsive hyaluronic acid (HA) delivery platform was designed for ocular applications. PLGA‐PEG copolymers with D,L‐LA/GA ratio of 15/1, PLGA/PEG ratio of 2/1, PEG Mw of 1500 Da, and Mw of about 6 KDa gelled at 35 °C, were optically transparent, had a modulus less than 350 Pa and were used for HA release studies. This work also demonstrates, for the first time, an extended and controlled release of HA, beyond 2 weeks, from injectable hydrogels modified with a noncovalent interacting agent, poly(L‐lysine). Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the nonmodified hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48678.”

Technical White-Paper on PLGA/PLA/PLCL degradation properties available from PolySciTech

Biodegradable polymers such as PLGA are all alkyl polyesters which undergo hydrolysis to break down into residues and oligomers. The time over which this process occurs varies widely based on the molecular weight and chemical makeup (LA:GA ratio, etc.) of the polymers. Recently, PolySciTech (www.polyscitech.com) concluded a 9-month study on select polymers (AP081, AP086, AP089, AP091, AP120, AP136, AP178, and AP190) tracking their mass loss and molecular weight changes as they degraded in water at 37 ⁰C. The results of this degradation study can be seen on the technical white-paper here (http://akinainc.com/pdf/Whitepaper-polymer-degradation.pdf).

Tuesday, November 12, 2019

PLGA from PolySciTech used in optimization of nanoparticle encapsulation of chemotherapeutic agent.

The single-emulsion technique is a widely used methodology to form nanoparticles when the drug to be loaded is hydrophobic enough to be directly dissolved into the organic solvent along with the polymer. The exact size and loading efficiency of these particles varies based on the manufacturing parameters and these can be optimized to provide for the highest quality nanoparticles. Recently, researchers at University of Houston used PLGA (AP041) from PolySciTech (www.polyscitech.com) and single-emulsion based techniques to optimize the nanoparticle encapsulation method for a chemotherapy drug. This research holds promise for improved therapy against cancer. Read more: Holley, Claire K., Bridgett Sinquefield, and Sheereen Majd. "Optimization of the Single Emulsion Method for Encapsulation of a Cancer Drug in Nanoparticles." In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 1078-1081. IEEE, 2019. https://ieeexplore.ieee.org/abstract/document/8857458/

“Abstract: The goal of this study is to apply and optimize the single emulsion technique for encapsulation of an anti-tumor drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), as a step towards targeted delivery of this drug. We previously showed that the nanoprecipitation technique can effectively produce PLGA NPs carrying this drug. Here, we aim to examine the single emulsion technique as an alternative for the preparation of these NPs and to compare the resultant NPs to those from nanoprecipitation. We fabricated NPs with variations in (i) injection rate, (ii) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (iii) concentration of PLGA in the organic phase. These NPs were characterized for size, surface potential, and encapsulation efficiency. The results revealed that increasing the injection rate (from manual addition to 90 mL/hr via syringe pump) greatly reduced the size of NPs (by 48%) and decreasing the PVA concentration in the aqueous phase (from 5 to 1% w/v) further reduced the NP size (by 32%) to 329 nm. All tested NP formulations had negative surface potential, suggesting good colloidal stability for these NPs. Focusing on the optimal injection rate and PVA percentage, we found that reducing the concentration of PLGA, from 100 to 1 mg/mL, significantly reduced the NP size to 136 nm, which is close to the optimal range for cancer therapeutic delivery. NPs produced by this method had a high encapsulation efficiency of 77% for Dp44mT and reducing the PLGA concentration slightly lowered this value to 74%. Overall, these NPs were comparable to those produced by nanoprecipitation and can thus, serve as an effective alternative for delivery of Dp44mT to cancer cells.”

mPEG-PLA and PLA-PEG-COOH from PolySciTech used in development of prostate cancer therapy

Ensuring appropriate delivery of drug molecules to the location of action is critical for their efficacy. Prostate cancer is one of the most common types of cancer in men and can be aggressive and spread. This type of cancer can be targeted by a specific antigen. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (AK054) and PLA-PEG-COOH (AI030) from PolySciTech (www.polyscitech.com) to create galbanic acid/docetaxel loaded nanoparticles decorated with a targeting molecule for prostate cancer treatment. This research holds promise to provide for improved therapies against this common type of cancer. Read more: Afsharzadeh, Maryam, Maryam Hashemi, Maryam Babaei, Khalil Abnous, and Mohammad Ramezani. "PEG‐PLA nanoparticles decorated with small‐molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells." Journal of cellular physiology (2019). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29339

“Abstract: Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy.”

Friday, November 1, 2019

mPEG-PLA from PolySciTech used in development of continuous nanoparticle generation system for large-scale nanoparticle production

Nanoparticles are generated by the carefully controlled solvent extraction of a polymer solution under emulsifying conditions which causes the polymer to self-form into small spheres (nanoparticles). There are many ways to generally accomplish this, however most have to be done in batch mode and are limited in scale. Recently, researchers at ETH Zurich (Switzerland) used mPEG-PLA (AK056) from PolySciTech (www.polyscitech.com) for generation of nanoparticles using a novel coaxial mixing system which can rapidly generate large quantities of particles. This research holds promise to enable large-scale production of nanoparticles. Read more: Bovone, Giovanni, Elia A. Guzzi, and Mark W. Tibbitt. "Flow‐based reactor design for the continuous production of polymeric nanoparticles." AIChE Journal (2019). https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/aic.16840

“Abstract: Polymeric nanoparticles (NPs) are versatile and effective drug delivery systems (DDS) that can be produced via nanoprecipitation of block copolymers. Yet, translation into clinical products has been limited. Thus, methods for NP production that enable rapid formulation screening and continuous production are needed. Toward this end, we engineered a coaxial jet mixer (CJM) for controlled and continuous nanoprecipitation in flow. The CJM enabled continuous assembly of poly(ethylene glycol)‐block‐polylactide NPs with various co‐solvents and was compared to batch nanoprecipitation. Other fabricated microfluidic devices were suitable for small scale formulation screening but more limited in scalable and continuous processes. In contrast, the CJM was tolerant to all water‐miscible solvents tested, enabled formulation screening, and scalable production of NPs and DDS. In total, the CJM provides a complementary approach to the process engineering of polymeric NP formation that can be used broadly for formulation screening and production.”