scholarly journals Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival

2020 ◽  
Vol 6 (35) ◽  
pp. eaba5573
Author(s):  
María M. Coronel ◽  
Karen E. Martin ◽  
Michael D. Hunckler ◽  
Graham Barber ◽  
Eric B. O’Neill ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Checkpoint Blockade ◽  
Poly Ethylene Glycol ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Synthetic Biomaterial ◽  
Poly Ethylene ◽  
L1 Protein

Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct “reprogramming” of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo. Furthermore, local induction of allograft acceptance is achieved in a murine model of diabetes only when receiving the SA-PD-L1–presenting biomaterial in combination with a brief rapamycin treatment. Immune characterization revealed an increase in T regulatory and anergic cells after SA-PD-L1-microgel delivery, which was distinct from naïve and biomaterial alone microenvironments. Engineering the local microenvironment via biomaterial delivery of checkpoint proteins has the potential to advance cell-based therapies, avoiding the need for systemic chronic immunosuppression.

Exploring the in vivo fates of RGD and PEG modified PEI/DNA nanoparticles by optical imaging and optoacoustic imaging

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112552-112561 ◽  
Author(s):  
Lin Lin ◽  
Jie Chen ◽  
Zhaopei Guo ◽  
Wantong Song ◽  
Dawei Zhang ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Optical Imaging ◽  
Tumor Targeting ◽  
Peptide Ligands ◽  
Poly Ethylene Glycol ◽  
Optoacoustic Imaging ◽  
Dna Nanoparticles ◽  
Poly Ethylene

To improve the abilities of long-term circulation and tumor targeting, poly(ethylene glycol) modified polyethylenimine with or without RGD peptide ligands were synthesized and evaluated in detail.

scholarly journals Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 605
Author(s):  
Marie-Emérentienne Cagnon ◽  
Silvio Curia ◽  
Juliette Serindoux ◽  
Jean-Manuel Cros ◽  
Feifei Ng ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Surface Erosion ◽  
Sustained Delivery ◽  
Trimethylene Carbonate ◽  
Poly Ethylene Glycol ◽  
In Situ Forming ◽  
Poly Ethylene ◽  
Long Acting

This article describes the utilization of (methoxy)poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) ((m)PEG–PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.

scholarly journals Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Amphiphilic Copolymers for Long-Acting Injectables: Synthesis, Non-Acylating Performance and In Vivo Degradation

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1438
Author(s):  
Silvio Curia ◽  
Feifei Ng ◽  
Marie-Emérentienne Cagnon ◽  
Victor Nicoulin ◽  
Adolfo Lopez-Noriega
Keyword(s):  
Ethylene Glycol ◽  
Ring Opening ◽  
Gel Chromatography ◽  
Amphiphilic Copolymers ◽  
Trimethylene Carbonate ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene ◽  
Long Acting ◽  
In Vivo Degradation

This article presents the evaluation of diblock and triblock poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) amphiphilic copolymers (PEG-PTMCs) as excipients for the formulation of long-acting injectables (LAIs). Copolymers were successfully synthesised through bulk ring-opening polymerisation. The concomitant formation of PTMC homopolymer could not be avoided irrespective of the catalyst amount, but the by-product could easily be removed by gel chromatography. Pure PEG-PTMCs undergo faster erosion in vivo than their corresponding homopolymer. Furthermore, these copolymers show outstanding stability compared to their polyester analogues when formulated with amine-containing reactive drugs, which makes them particularly suitable as LAIs for the sustained release of drugs susceptible to acylation.

scholarly journals Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dobrin Draganov ◽  
Zhen Han ◽  
Aamir Rana ◽  
Nitasha Bennett ◽  
Darrell J. Irvine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Synergistic Activity ◽  
Primary Tumors ◽  
T Cell Infiltration ◽  
Cancer Cell Death ◽  
Bona Fide

AbstractWe show that treatment with the FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis which operates in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio. While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p = 0.03) and promoted complete responses (p < 0.01), also leading to immunity against contralateral re-challenge with demonstrated anti-tumor immune responses. Going beyond primary tumors, this combination achieved significant reduction in relapse after neoadjuvant (p = 0.03) and adjuvant treatment (p < 0.001), and potential cures in metastatic disease (p < 0.001). Statistical modeling confirmed bona fide synergistic activity in both the adjuvant (p = 0.007) and metastatic settings (p < 0.001). Ivermectin has dual immunomodulatory and ICD-inducing effects in breast cancer, converting cold tumors hot, thus represents a rational mechanistic partner with checkpoint blockade.

Hierarchical Self-Assembly of Microgel-Modified Biomaterials Surfaces

2014 ◽  
Vol 1622 ◽  
pp. 1-6
Author(s):  
Yong Wu ◽  
Jing Liang ◽  
Qichen Wang ◽  
Matthew Libera
Keyword(s):  
Self Assembly ◽  
Scale Effects ◽  
Control Surface ◽  
Poly Ethylene Glycol ◽  
Hydrogel Particles ◽  
Network Properties ◽  
Tissue Cells ◽  
Poly Ethylene ◽  
Non Line Of Sight

ABSTRACTMicrogels are hydrogel particles with micron and sub-micron diameters. They have beendeveloped, studied, and exploited for a broad range of applications because of their uniquecombination of size, soft mechanical properties, and controllable network properties. We havebeen using microgels to modulate the properties of surfaces to differentially control theirinteractions with tissue cells and bacteria. The long-term goal is to create biomaterials thatpromote healing while simultaneously inhibiting infection. Because poly(ethylene glycol) [PEG]is used in a number of FDA-approved products and has well-known antifouling properties, wework primarily with PEG-based microgels. We render these anionic either by copolymerizationwith monomeric acids or by blending with polyacids. Both methods produce pH-dependentnegative charge. Surfaces, both planar 2-D surfaces as well as topographically complex 3-Dsurfaces, can be modified using a hierarchy of non-line-of-sight electrostatic depositionprocesses that create biomaterials surfaces whose cell adhesiveness is modulated by a submonolayerof microgels. Average inter-microgel spacings of 1-2 microns exploit naturaldifferences between staphylococcal bacteria and tissue cells, which open the opportunity todifferentially control surface interactions with them based on length-scale effects. Afterdeposition, the microgels can be loaded with a variety of small-molecule, cationic antimicrobials.The details of loading depend on the relative sizes of the antimicrobials and the microgelnetwork structure as well as on the amount and spatial distribution of electrostatic charge withinboth the microgel and on the antimicrobial. The exposed surface between microgels can befurther modified by the adsorption of adhesion-promoting proteins such as fibronectin viaelectrostatic interaction. This approach combines a rich interplay of microgel structure andchemistry as a key component in a simple and translatable approach to modulate the surfaceproperties of next-generation biomaterials.

scholarly journals Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

2018 ◽  
Vol 47 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Sivan Yogev ◽  
Ayelet Shabtay-Orbach ◽  
Abraham Nyska ◽  
Boaz Mizrahi
Keyword(s):  
Block Copolymer ◽  
Ethylene Glycol ◽  
Medical Devices ◽  
Poly Lactic Acid ◽  
Poly Ethylene Glycol ◽  
Thermoresponsive Polymers ◽  
Wide Range ◽  
Poly Ethylene

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

In vivo and in vitro degradation of poly(ether ester) block copolymers based on poly(ethylene glycol) and poly(butylene terephthalate)

Biomaterials ◽  
2004 ◽  
Vol 25 (2) ◽  
pp. 247-258 ◽  
Author(s):  
A.A. Deschamps ◽  
A.A. van Apeldoorn ◽  
H. Hayen ◽  
J.D. de Bruijn ◽  
U. Karst ◽  
...  
Keyword(s):  
Block Copolymers ◽  
Ethylene Glycol ◽  
Poly Ethylene Glycol ◽  
In Vitro Degradation ◽  
Butylene Terephthalate ◽  
Poly Ethylene ◽  
Ether Ester

In vitro and in vivo study of poly(ethylene glycol) conjugated ketoprofen to extend the duration of action

2007 ◽  
Vol 341 (1-2) ◽  
pp. 50-57 ◽  
Author(s):  
Hoo-Kyun Choi ◽  
Myung-Kwan Chun ◽  
Se Hee Lee ◽  
Mee Hee Jang ◽  
Hee Doo Kim ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
In Vivo Study ◽  
Poly Ethylene Glycol ◽  
Duration Of Action ◽  
Poly Ethylene

Poly(ethylene glycol)-Conjugation and Deoxygenation Enable Long-Term Preservation of Hemoglobin-Vesicles as Oxygen Carriers in a Liquid State

2000 ◽  
Vol 11 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Hiromi Sakai ◽  
Ken-ichi Tomiyama ◽  
Keitaro Sou ◽  
Shinji Takeoka ◽  
Eishun Tsuchida
Keyword(s):  
Ethylene Glycol ◽  
Liquid State ◽  
Oxygen Carriers ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene ◽  
Long Term Preservation
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