PLGA-PEG-PLGA from PolySciTech used in development of thermogel for treatment of corneal injuries.

 

Even relatively minor ocular injuries can lead to downstream blindness due to localized inflammation and overgrowth of blood vessels occurring in response to the injury. This result can be prevented by TNF and VEGF inhibitors however this requires consistent application of the drugs during the healing process. Researchers at Harvard Medical School, Massachusetts Eye and Ear Infirmary, and University of New Mexico School of Medicine utilized PLGA-PEG-PLGA (AK141) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a thermogel for long-acting delivery of adalimumab and aflibercept for ocular injection. This research holds promise to reduce the incidence of blindness by offering a new option for treatment of ocular damage. Read more: Zhou, Chengxin, Fengyang Lei, Pui-Chuen Hui, Natalie Wolkow, Claes Dohlman, Demetrios G. Vavvas, James Chodosh, and Eleftherios I. Paschalis. "A novel sustained release therapy of combined VEGF and TNF-α inhibitors leads to pan-ocular protection for months after severe ocular trauma." bioRxiv (2023): 2023-03. https://www.biorxiv.org/content/10.1101/2023.03.14.531626.abstract

“Purpose: To develop a clinically feasible and practical therapy for multi-ocular protection following ocular injury by using a thermosensitive drug delivery system (DDS) for sustained delivery of TNF-alpha and VEGF inhibitors to the eye. Methods: A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock polymer) loaded with 0.7mg of adalimumab and 1.4 mg of aflibercept was injected subconjunctivally in Dutch-belted pigmented rabbits after corneal alkali injury. The polymer was tuned to transition from liquid to gel upon contact with body temperature without need of a catalyst. Control rabbits received 2mg of IgG loaded DDS or 1.4mg aflibercept loaded DDS. Animals were followed for 3 months and assessed for tolerability and prevention of corneal neovascularization (NV), improvement of corneal re-epithelialization, inhibition of retinal ganglion cell (RGC) and optic nerve axon loss, and inhibition of immune cell infiltration into the cornea. Drug release kinetics was assessed in vivo using aqueous humor protein analysis. Results: A single subconjunctival administration of dual anti-TNF-alpha/anti-VEGF DDS achieved sustained 3-month delivery of antibodies to the anterior chamber, iris, ciliary body, and retina. Administration after corneal alkali burn suppressed CD45+ immune cell infiltration into the cornea, completely inhibited cornea NV for 3 months, accelerated corneal re-epithelialization and wound healing, and prevented RGC and optic nerve axon loss at 3 months. In contrast, anti-VEGF alone or IgG DDS treatment led to persistent corneal epithelial defect, increased infiltration of CD45+ immune cells into the cornea, and significant loss of RGCs and optic nerve axons at 3 months. Aqueous humor protein analysis showed first-order release kinetics without adverse effects at the injection site. Conclusion: Sustained concomitant inhibition of TNF-alpha and VEGF using a biodegradable, slow-release thermosensitive DDS provides significant ocular protection and prevents corneal neovascularization and irreversible damage to retina and optic nerve after corneal alkali injury. This therapeutic approach has the potential to dramatically improve the outcomes of severe ocular injuries in patients.”

Video: https://youtu.be/l9PyjfDNJAk

PLCL from PolySciTech used in development of heart valve replacement for tissue engineering

 

Tissue engineering is a process where a cell scaffold or other structure is provided to allow for damaged or missing parts of the human body to regrow. The bioresorbable scaffold should match the mechanical properties of the tissue to be replaced as well as provide a surface for cells to attach to and grow on. Researchers at University of Missouri used PLCLs with a range of LA:CL ratios (cat# AP147, AP015, AP151, AP262) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a mechanically robust and elastic heart valve replacement. This research holds promise to regrow or replace damaged portions of heart tissue. Read more: Snyder, Yuriy, and Soumen Jana. "Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering." ACS Biomaterials Science & Engineering (2023). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c01430

“Heart valve leaflets have a complex trilayered structure with layer-specific orientations, anisotropic tensile properties, and elastomeric characteristics that are difficult to mimic collectively. Previously, trilayer leaflet substrates intended for heart valve tissue engineering were developed with nonelastomeric biomaterials that cannot deliver native-like mechanical properties. In this study, by electrospinning polycaprolactone (PCL) polymer and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet substrates with native-like tensile, flexural, and anisotropic properties and compared them with trilayer PCL leaflet substrates (as control) to find their effectiveness in heart valve leaflet tissue engineering. These substrates were seeded with porcine valvular interstitial cells (PVICs) and cultured for 1 month in static conditions to produce cell-cultured constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity but higher anisotropy and flexibility than PCL leaflet substrates. These attributes contributed to more significant cell proliferation, infiltration, extracellular matrix production, and superior gene expression in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured constructs. Further, the PCL/PLCL constructs showed better resistance to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates with native-like mechanical and flexural properties could significantly improve heart valve tissue engineering. KEYWORDS: elastomer electrospinning trilayer tissue engineering heart valve leaflet calcification”

Video: https://youtu.be/sO_s_RNSTJ8

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research on preventing cardiovascular restenosis

 

Cardiovascular disease is the leading cause of all deaths worldwide. Restenosis is the re-narrowing of a blood vessel after catheterization and can lead to down-stream heart problems even after surgical intervention. Researchers at University of Virginia used PLGA-PEG-PLGA (cat# AK012) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a thermogelling delivery vehicle for EED226 to deliver it in place in the periadventitial space of the injured artery and observe its effects. This research holds promise to further understand and prevent in-stent restenosis. Read more: Zhang, Mengxue, Jing Li, Qingwei Wang, Go Urabe, Runze Tang, Yitao Huang, Jose Verdezoto Mosquera et al. "Gene-repressing epigenetic reader EED unexpectedly enhances cyclinD1 gene activation." Molecular Therapy-Nucleic Acids (2023). https://www.cell.com/molecular-therapy-family/nucleic-acids/pdf/S2162-2531(23)00044-6.pdf

“Epigenetically switched, proliferative vascular smooth muscle cells (SMCs) form neointima, engendering stenotic diseases. Histone-3 lysine-27 trimethylation (H3K27me3) and acetylation (H3K27ac) marks are associated with gene repression and activation, respectively. The polycomb protein embryonic ectoderm development (EED) reads H3K27me3 and also enhances its deposition, hence a canonical gene-repressor. However, herein we found an unexpected role for EED in activating the bona fide pro-proliferative gene Ccnd1 (cyclinD1). EED overexpression in SMCs increased Ccnd1 mRNA, seemingly contradicting its gene-repressing function. Yet consistently, EED co-immunoprecipitated with gene-activating H3K27ac reader BRD4, and they co-occupied at both mitogen-activated Ccnd1 and mitogen-repressed P57 (bona fide anti-proliferative gene), as indicated by chromatin immunoprecipitation-qPCR. These results were abolished by an inhibitor of either the EED/H3K27me3 or BRD4/H3K27ac reader function. In accordance, elevating BRD4 increased H3K27me3. In vivo, while EED was upregulated in rat and human neointimal lesions, selective EED inhibition abated angioplasty-induced neointima and reduced cyclinD1 in rat carotid arteries. Thus, results uncover a previously unknown role of EED in Ccnd1 activation, likely via its cooperativity with BRD4 that enhances each other’s reader function, i.e. activating pro-proliferative Ccnd1 while repressing anti-proliferative P57. As such, this study confers mechanistic implications for the epigenetic intervention of neointimal pathology.”

Video: https://youtu.be/9_6b6nn1MR0

PLGA-PEG-Mal, PLGA-PEG from PolySciTech used in development of cancer diagnosing nanobubbles

 

Ultrasound is a widely applicable and robust imaging technique that can determine internal features of humans in a non-invasive manner. One way to assist clinicians in treating cancer is to render the tumors visible by ultrasound so that they can be readily diagnosed and identified. Researchers at University of Illinois Urbana-Champaign Used PLGA (cat# AP154) as well as PLGA-PEG, and PLGA-PEG-Mal from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create targeted nanoparticles loaded with fluorescent dye and ultrasound contrast agent which attach to prostate cancer by ligand binding. This research holds promise to improve diagnostic techniques for treatment of cancer. Read More: Zhao, Shensheng, Leanne Lee, Yang Zhao, N. Liang, and Y. Chen. "Photoacoustic signal enhancement in dual-contrast gastrin-releasing peptide receptor-targeted nanobubbles." Frontiers in Bioengineering and Biotechnology 11 (2023). https://europepmc.org/article/pmc/pmc9887164

“Translatable imaging agents are a crucial element of successful molecular imaging. Photoacoustic molecular imaging relies on optical absorbing materials to generate a sufficient signal. However, few materials approved for human use can generate adequate photoacoustic responses. Here we report a new nanoengineering approach to further improve photoacoustic response from biocompatible materials. Our study shows that when optical absorbers are incorporated into the shell of a gaseous nanobubble, their photoacoustic signal can be significantly enhanced compared to the original form. As an example, we constructed nanobubbles using biocompatible indocyanine green (ICG) and biodegradable poly(lactic-co-glycolic acid) (PLGA). We demonstrated that these ICG nanobubbles generate a strong ultrasound signal and almost four-fold photoacoustic signal compared to the same concentration of ICG solution; our theoretical calculations corroborate this effect and elucidate the origin of the photoacoustic enhancement. To demonstrate their molecular imaging performance, we conjugated gastrin-releasing peptide receptor (GRPR) targeting ligands with the ICG nanobubbles. Our dual photoacoustic/ultrasound molecular imaging shows a more than three-fold enhancement in targeting specificity of the GRPR-targeted ICG nanobubbles, compared to untargeted nanobubbles or prostate cancer cells not expressing GRPR, in a prostate cancer xenograft mouse model in vivo. Keywords: cancer diagnosis, photoacoustic, ultrasound, molecular imaging, multimodal imaging, nanobubbles, GRPR, ICG”

Video: https://youtu.be/nXRUeyuLsoI

Fluorescent PLGA from PolySciTech used in Development of nanoparticles for pancreatic cancer therapy

 

Pancreatic cancer is very difficult to treat and remains the leading cause of cancer-related deaths. Researchers at The Hebrew University of Jerusalem utilized PLGA-CY5 (cat# AV034) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently traceable nanoparticles. They used these for testing the uptake of SiRNA loaded nanoparticles towards pancreatic cancer. This research holds promise to improve therapy against this fatal disease. Read More: Agbaria, Majd, Doaa Jbara-Agbaria, Etty Grad, Meital Ben-David-Naim, Gil Aizik, and Gershon Golomb. "Nanoparticles of VAV1 siRNA combined with LL37 peptide for the treatment of pancreatic cancer." Journal of Controlled Release 355 (2023): 312-326. https://www.sciencedirect.com/science/article/pii/S0168365923000937

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related death, and it is highly resistant to therapy owing to its unique extracellular matrix. VAV1 protein, overexpressed in several cancer diseases including pancreatic cancer (PC), increases tumor proliferation and enhances metastases formation, which are associated with decreased survival. We hypothesized that an additive anti-tumor effect could be obtained by co-encapsulating in PLGA nanoparticles (NPs), the negatively charged siRNA against VAV1 (siVAV1) with the positively charged anti-tumor LL37 peptide, as a counter-ion. Several types of NPs were formulated and were characterized for their physicochemical properties, cellular internalization, and bioactivity in vitro. NPs' biodistribution, toxicity, and bioactivity were examined in a mice PDAC model. An optimal siVAV1 formulation (siVAV1-LL37 NPs) was characterized with desirable physicochemical properties in terms of nano-size, low polydispersity index (PDI), neutral surface charge, high siVAV1 encapsulation efficiency, spherical shape, and long-term shelf-life stability. Cell assays demonstrated rapid engulfment by PC cells, a specific and significant dose-dependent proliferation inhibition, as well as knockdown of VAV1 mRNA levels and migration inhibition in VAV1+ cells. Treatment with siVAV1-LL37 NPs in the mice PDAC model revealed marked accumulation of NPs in the liver and in the tumor, resulting in an increased survival rate following suppression of tumor growth and metastases, mediated via the knockdown of both VAV1 mRNA and protein levels. This proof-of-concept study validates our hypothesis of an additive effect in the treatment of PC facilitated by co-encapsulating siVAV1 in NPs with LL37 serving a dual role as a counter ion as well as an anti-tumor agent.

Video: https://youtu.be/RdZzFuErcbk

PLGA-PEG-Mal from PolySciTech used in development of peptide-based nanoparticle treatment of prostate cancer

 

Prostate cancer is the second most prevalent cause of cancer deaths in males, worldwide. There are many therapies available, however most patients with metastatic prostate cancer suffer relapse. Researchers at Barcelona Institute of Science and Technology, Institute for Advanced Chemistry of Catalonia (Spain), and Eindhoven University of Technology (Netherlands) used PLGA-PEG-Maleimide (cat# AI110) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to conjugate on WQP, a targeting peptide. They created nanoparticles and tested their ability to target towards prostate cells and provide treatment for prostate cancer. This research holds promise to improve therapy against prostate cancer in the future. Read More: Murar, Madhura, Silvia Pujals, and Lorenzo Albertazzi. "Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting." Nanoscale Advances (2023). https://pubs.rsc.org/en/content/articlehtml/2023/na/d2na00601d

“The concept of selective tumor targeting using nanomedicines has been around for decades; however, no targeted nanoparticle has yet reached the clinic. A key bottleneck is the non-selectivity of targeted nanomedicines in vivo, which is attributed to the lack of characterization of their surface properties, especially the ligand number, thereby calling for robust techniques that allow quantifiable outcomes for an optimal design. Multivalent interactions comprise multiple copies of ligands attached to scaffolds, allowing simultaneous binding to receptors, and they play an important role in targeting. As such, ‘multivalent’ nanoparticles facilitate simultaneous interaction of weak surface ligands with multiple target receptors resulting in higher avidity and enhanced cell selectivity. Therefore, the study of weak binding ligands for membrane-exposed biomarkers is crucial for the successful development of targeted nanomedicines. Here we carried out a study of a cell targeting peptide known as WQP having weak binding affinity for prostate specific membrane antigen, a known prostate cancer biomarker. We evaluated the effect of its multivalent targeting using polymeric NPs over its monomeric form on the cellular uptake in different prostate cancer cell lines. We developed a method of specific enzymatic digestion to quantify the number of WQPs on NPs having different surface valencies and observed that increasing valencies resulted in a higher cellular uptake of WQP-NPs over the peptide alone. We also found that WQP-NPs showed higher uptake in PSMA over-expressing cells, attributed to a stronger avidity for selective PSMA targeting. This kind of strategy can be useful for improving the binding affinity of a weak ligand as a means for selective tumor targeting.”

Video: https://youtu.be/nnzHrU3gjlw

PLGA from PolySciTech used in development of genipin modified sutures for surgical repair of tendons

 

Sutures mechanically hold tissue closed in place so that wounds or surgical incisions can heal. They can also provide a platform for drug release or bioactive surface which can have additional therapeutic effects. Researchers at Balgrist University Hospital, ETH Zurich, and Cantonal Hospital Lucerne used PLGA (AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create coated genipin-coated sutures for tendon repair. They applied this modified suture to repairing tendons which typically do not heal well after injury. This research holds promise to improve surgical repairs for traumatic injuries. Read more: Götschi, Tobias, Anne-Gita Scheibler, Patrick Jaeger, Karl Wieser, Claude Holenstein, Jess G. Snedeker, and Roland S. Camenzind. "Improved suture pullout through genipin-coated sutures in human biceps tendons with spatially confined changes in cell viability." Clinical Biomechanics (2023): 105907. https://www.sciencedirect.com/science/article/pii/S0268003323000384

“Highlights: Suture cut-through is a common cause of rotator cuff repair failure. Coating the suture with collagen cross-linker enhances strength of suture-tendon interface. Short-term in vitro culturing reduces tenocyte viability near suture. No difference in cell viability between treatment groups at 3 mm + from suture. Abstract: The suture-tendon interface often constitutes the point of failure in tendon suture repair. In the present study, we investigated the mechanical benefit of coating the suture with a cross-linking agent to strengthen the nearby tissue after suture placement in human tendons and we assessed the biological implications regarding tendon cell survival in-vitro. Freshly harvested human biceps long head tendons were randomly allocated to control (n = 17) or intervention (n = 19) group. According to the assigned group, either an untreated or a genipin-coated suture was inserted into the tendon. 24 h after suturing, mechanical testing composed of cyclic and ramp-to-failure loading was performed. Additionally, 11 freshly harvested tendons were used for short-term in vitro cell viability assessment in response to genipin-loaded suture placement. These specimens were analyzed in a paired-sample setting as stained histological sections using combined fluorescent/light microscopy. Tendons stitched with a genipin-coated suture sustained higher forces to failure. Cyclic and ultimate displacement of the tendon-suture construct remained unaltered by the local tissue crosslinking. Tissue crosslinking resulted in significant cytotoxicity in the direct vicinity of the suture (<3 mm). At larger distances from the suture, however, no difference in cell viability between the test and the control group was discernable. The repair strength of a tendon-suture construct can be augmented by loading the suture with genipin. At this mechanically relevant dosage, crosslinking-induced cell death is confined to a radius of <3 mm from the suture in the short-term in-vitro setting. These promising results warrant further examination in-vivo. Keywords: Tendon Suture Soft tissue repair Collagen crosslinking Mechanical testing Cell viability”

Video: https://youtu.be/GWGbUs5gaF4