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Isaac AH, Recalde Phillips SY, Ruben E, Estes M, Rajavel V, Baig T, Paleti C, Landsgaard K, Lee RH, Guda T, Criscitiello MF, Gregory C, Alge DL. Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering. Nat Commun 2024; 15:3283. [PMID: 38637507 PMCID: PMC11026400 DOI: 10.1038/s41467-024-46327-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/22/2024] [Indexed: 04/20/2024] Open
Abstract
While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.
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Affiliation(s)
- Alisa H Isaac
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
- Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio, San Antonio, TX, USA
- Department of Cell Systems and Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA
| | | | - Elizabeth Ruben
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Matthew Estes
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Varsha Rajavel
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Talia Baig
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Carol Paleti
- Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, USA
| | - Kirsten Landsgaard
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Ryang Hwa Lee
- Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, USA
| | - Teja Guda
- Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio, San Antonio, TX, USA
- Department of Cell Systems and Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA
| | - Michael F Criscitiello
- Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA
| | - Carl Gregory
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA
- Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, College Station, TX, USA
| | - Daniel L Alge
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.
- Department of Materials Science and Engineering, Texas A&M University, College Station, TX, USA.
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2
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Park GW, Park N, Kuk JC, Shin EJ, Lim DR. Anaphylactic shock induced by polyethylene glycol after bowel preparation for the colorectal cancer surgery: A case report. World J Clin Cases 2023; 11:5589-5594. [PMID: 37637691 PMCID: PMC10450373 DOI: 10.12998/wjcc.v11.i23.5589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/27/2023] [Accepted: 07/25/2023] [Indexed: 08/16/2023] Open
Abstract
BACKGROUND Polyethylene glycol (PEG) is widely used as an additive because of its hydrophilic and chemically inert properties. However, there are been increasing reports of PEG allergies, including anaphylaxis, although they are still rare. This case report aims to raise awareness, that the commonly used bowel cleansing agent containing PEG can cause serious allergic reactions. CASE SUMMARY Prior to surgery for sigmoid colon cancer, a 63-year-old man was prescribed a bowel cleansing agent containing PEG. Within 30 min of ingestion, he developed symptoms of anaphylactic shock and did not respond to initial intramuscular epinephrine injection. Under diagnosis of anaphylaxis to PEG, he was stabilized with fluid hydration and continuous norepinephrine infusion. CONCLUSION While allergic reactions to PEG are rare, they can be life-threatening. Therefore, it is crucial for clinicians to be aware of this possibility and to diagnose and resuscitate patients immediately.
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Affiliation(s)
- Go Woon Park
- Department of General Surgery, Soonchunhyang Bucheon Hospital, Bucheon 14584, South Korea
| | - Nahyeon Park
- Department of General Surgery, Soonchunhyang Bucheon Hospital, Bucheon 14584, South Korea
| | - Jung Cheol Kuk
- Department of General Surgery, Soonchunhyang Bucheon Hospital, Bucheon 14584, South Korea
| | - Eung Jin Shin
- Department of General Surgery, Soonchunhyang Bucheon Hospital, Bucheon 14584, South Korea
| | - Dae Ro Lim
- Department of General Surgery, Soonchunhyang Bucheon Hospital, Bucheon 14584, South Korea
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3
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Ibrahim M, Ramadan E, Elsadek NE, Emam SE, Shimizu T, Ando H, Ishima Y, Elgarhy OH, Sarhan HA, Hussein AK, Ishida T. Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products. J Control Release 2022; 351:215-230. [PMID: 36165835 DOI: 10.1016/j.jconrel.2022.09.031] [Citation(s) in RCA: 149] [Impact Index Per Article: 49.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/12/2022] [Accepted: 09/14/2022] [Indexed: 11/29/2022]
Abstract
Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.
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Affiliation(s)
- Mohamed Ibrahim
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Eslam Ramadan
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Nehal E Elsadek
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
| | - Sherif E Emam
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Taro Shimizu
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
| | - Hidenori Ando
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
| | - Yu Ishima
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
| | - Omar Helmy Elgarhy
- Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Hatem A Sarhan
- Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Amal K Hussein
- Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Tatsuhiro Ishida
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
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4
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Anaphylaxis to Excipients in Current Clinical Practice: Evaluation and Management. Immunol Allergy Clin North Am 2022; 42:239-267. [PMID: 35469617 PMCID: PMC9907103 DOI: 10.1016/j.iac.2021.12.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Excipients are the inactive ingredients in a drug or product that help to stabilize, preserve, or enhance the pharmacokinetics and bioavailability of the active ingredients. Excipient allergy is rare and hence often missed or misdiagnosed due to lack of awareness of the need to carefully review all drug ingredients. For the patient, excipient allergy can be frightening and potentially disruptive to health care delivery. This narrative review provides a clinically oriented, international, collaborative perspective on excipient allergy testing, management of future health care safety, limitations in our testing modalities, and barriers to optimal care.
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5
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MacCuaig WM, Fouts BL, McNally MW, Grizzle WE, Chuong P, Samykutty A, Mukherjee P, Li M, Jasinski J, Behkam B, McNally LR. Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic Pancreatic Cancer. ACS APPLIED MATERIALS & INTERFACES 2021; 13:49614-49630. [PMID: 34653338 PMCID: PMC9783196 DOI: 10.1021/acsami.1c09379] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Nanoparticles are widely studied as theranostic vehicles for cancer; however, clinical translation has been limited due to poor tumor specificity. Features that maximize tumor uptake remain controversial, particularly when using clinically relevant models. We report a systematic study that assesses two major features for the impact on tumor specificity, i.e., active vs passive targeting and nanoparticle size, to evaluate relative influences in vivo. Active targeting via the V7 peptide is superior to passive targeting for uptake by pancreatic tumors, irrespective of nanoparticle size, observed through in vivo imaging. Size has a secondary effect on uptake for actively targeted nanoparticles in which 26 nm nanoparticles outperform larger 45 and 73 nm nanoparticles. Nanoparticle size had no significant effect on uptake for passively targeted nanoparticles. Results highlight the superiority of active targeting over nanoparticle size for tumor uptake. These findings suggest a framework for optimizing similar nonaggregate nanoparticles for theranostic treatment of recalcitrant cancers.
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Affiliation(s)
- William M. MacCuaig
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, 73104, USA
- Department of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
| | - Benjamin L. Fouts
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, 73104, USA
| | - Molly W McNally
- Department of Surgery, University of Oklahoma, Oklahoma City, OK, 73104, USA
- Department of Cancer Biology, Wake Forest University, Winston-Salem, NC 27157, USA
| | - William E. Grizzle
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Phillip Chuong
- Department of Surgery, University of Louisville, Louisville, KY 40202, USA
| | - Abhilash Samykutty
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, 73104, USA
- Department of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
- Department of Cancer Biology, Wake Forest University, Winston-Salem, NC 27157, USA
| | | | - Min Li
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, 73104, USA
| | - Jacek Jasinski
- Conn Center Materials Characterization, University of Louisville, Louisville, KY 40202, USA
| | - Bahareh Behkam
- Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA, 24061, USA
| | - Lacey R. McNally
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, 73104, USA
- Department of Surgery, University of Oklahoma, Oklahoma City, OK, 73104, USA
- Department of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
- Department of Cancer Biology, Wake Forest University, Winston-Salem, NC 27157, USA
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6
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Immunization practices and risk of anaphylaxis: a current update, comprehensive of COVID-19 vaccination data. Curr Opin Allergy Clin Immunol 2021; 21:418-425. [PMID: 34269740 DOI: 10.1097/aci.0000000000000769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW This review aims to provide an updated report in regards to the correlation between vaccines and anaphylaxis and the related risk in the population. RECENT FINDINGS Initial reports showed higher incidence of anaphylaxis following messenger RNA COVID-19 vaccines compared with 'routine' vaccinations, likely influenced by the great attention paid to these 'new' vaccines. However, anaphylaxis has still to be considered quite rare and its incidence will be systematically reconsidered in the light of additional data collected. SUMMARY Adverse reactions to vaccines are commonly reported but most of them are nonspecific mild events, whereas vaccine-related anaphylaxis is considered a rare event, with an incidence rate equal to 1.3 cases per million vaccine doses administered. As anaphylaxis reports usually start to be reported to passive pharmacovigilance during postmarketing surveillance, the first data are used to be influenced by under- and over-reporting and lack of denominators and following studies are needed to confirm the causal relationship. This might create an initial overcautiously approach to new immunization practices but, being anaphylaxis a potential life-threatening event, every suspected contraindication has to be deepened to maximize effectiveness and safety profile and constantly redefined not to exclude an overestimated population group who could receive the vaccine uneventfully.
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7
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Caballero ML, Krantz MS, Quirce S, Phillips EJ, Stone CA. Hidden Dangers: Recognizing Excipients as Potential Causes of Drug and Vaccine Hypersensitivity Reactions. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2021; 9:2968-2982. [PMID: 33737254 PMCID: PMC8355062 DOI: 10.1016/j.jaip.2021.03.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/22/2021] [Accepted: 03/03/2021] [Indexed: 12/18/2022]
Abstract
Excipients are necessary as a support to the active ingredients in drugs, vaccines, and other products, and they contribute to their stability, preservation, pharmacokinetics, bioavailability, appearance, and acceptability. For both drugs and vaccines, these are rare reactions; however, for vaccines, they are the primary cause of immediate hypersensitivity. Suspicion for these "hidden dangers" should be high, in particular, when anaphylaxis has occurred in association with multiple chemically distinct drugs. Common excipients implicated include gelatin, carboxymethylcellulose, polyethylene glycols, and products related to polyethylene glycols in immediate hypersensitivity reactions and propylene glycol in delayed hypersensitivity reactions. Complete evaluation of a suspected excipient reaction requires detailed information from the product monograph and package insert to identify all ingredients that are present and to understand the function and structure for these chemicals. This knowledge helps develop a management plan that may include allergy testing to identify the implicated component and to give patients detailed information for future avoidance of relevant foods, drugs, and vaccines. Excipient reactions should be particularly considered for specific classes of drugs where they have been commonly found to be the culprit (eg, corticosteroids, injectable hormones, immunotherapies, monoclonal antibodies, and vaccines). We provide a review of the evidence-based literature outlining epidemiology and mechanisms of excipient reactions and provide strategies for heightened recognition and allergy testing.
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Affiliation(s)
| | - Matthew S Krantz
- Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn
| | - Santiago Quirce
- Department of Allergy, La Paz University Hospital, IdiPAZ, Madrid, Spain; Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
| | - Elizabeth J Phillips
- Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pharmacology, Vanderbilt School of Medicine, Nashville, Tenn; Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia
| | - Cosby A Stone
- Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
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8
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Frickenstein AN, Hagood JM, Britten CN, Abbott BS, McNally MW, Vopat CA, Patterson EG, MacCuaig WM, Jain A, Walters KB, McNally LR. Mesoporous Silica Nanoparticles: Properties and Strategies for Enhancing Clinical Effect. Pharmaceutics 2021; 13:570. [PMID: 33920503 PMCID: PMC8072651 DOI: 10.3390/pharmaceutics13040570] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/15/2021] [Accepted: 04/07/2021] [Indexed: 12/13/2022] Open
Abstract
Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations.
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Affiliation(s)
- Alex N. Frickenstein
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (C.A.V.); (W.M.M.)
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (J.M.H.); (M.W.M.)
| | - Jordan M. Hagood
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (J.M.H.); (M.W.M.)
| | - Collin N. Britten
- School of Chemical, Biological, and Materials Engineering, University of Oklahoma, Norman, OK 73019, USA; (C.N.B.); (B.S.A.); (K.B.W.)
| | - Brandon S. Abbott
- School of Chemical, Biological, and Materials Engineering, University of Oklahoma, Norman, OK 73019, USA; (C.N.B.); (B.S.A.); (K.B.W.)
| | - Molly W. McNally
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (J.M.H.); (M.W.M.)
| | - Catherine A. Vopat
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (C.A.V.); (W.M.M.)
| | - Eian G. Patterson
- Department of Biology, University of Oklahoma, Norman, OK 73019, USA;
| | - William M. MacCuaig
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA; (A.N.F.); (C.A.V.); (W.M.M.)
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (J.M.H.); (M.W.M.)
| | - Ajay Jain
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA;
| | - Keisha B. Walters
- School of Chemical, Biological, and Materials Engineering, University of Oklahoma, Norman, OK 73019, USA; (C.N.B.); (B.S.A.); (K.B.W.)
| | - Lacey R. McNally
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (J.M.H.); (M.W.M.)
- Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA;
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9
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Anaphylactic reactions to mRNA COVID-19 vaccines: A call for further study. Vaccine 2021; 39:2605-2607. [PMID: 33846043 PMCID: PMC8023205 DOI: 10.1016/j.vaccine.2021.03.073] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 03/20/2021] [Indexed: 11/02/2022]
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10
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Rossi A, Osborn L. A Case Report of Angioedema and Anaphylactic Shock Induced by Ingestion of Polyethylene Glycol. Clin Pract Cases Emerg Med 2020; 4:189-192. [PMID: 32426669 PMCID: PMC7219999 DOI: 10.5811/cpcem.2020.3.45218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 02/27/2020] [Accepted: 03/06/2020] [Indexed: 12/04/2022] Open
Abstract
Introduction We report one of few documented cases of a severe anaphylactic reaction with angioedema to polyethylene glycol (PEG). Case Report The patient presented 30 minutes after onset of his symptoms and quickly developed hypoxia and hypotension refractory to intramuscular epinephrine, intravenous fluids, methylprednisolone, and supplemental oxygen via non-rebreather mask. He ultimately required intubation, an epinephrine infusion, and admission to the medical intensive care unit. Discussion This case depicts a clinical reaction to PEG, a medication rarely implicated in severe anaphylaxis or angioedema. Conclusion The allergenic potential of PEG-containing products should be raised, and providers should have a heightened awareness of these potential side effects.
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Affiliation(s)
- Amy Rossi
- University of Texas at Houston, McGovern Medical School, Department of Emergency Medicine, Houston, Texas
| | - Lesley Osborn
- University of Texas at Houston, McGovern Medical School, Department of Emergency Medicine, Houston, Texas
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11
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Civit L, Theodorou I, Frey F, Weber H, Lingnau A, Gröber C, Blank M, Dambrune C, Stunden J, Beyer M, Schultze J, Latz E, Ducongé F, Kubbutat MHG, Mayer G. Targeting hormone refractory prostate cancer by in vivo selected DNA libraries in an orthotopic xenograft mouse model. Sci Rep 2019; 9:4976. [PMID: 30899039 PMCID: PMC6428855 DOI: 10.1038/s41598-019-41460-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 03/08/2019] [Indexed: 12/11/2022] Open
Abstract
The targeting of specific tissue is a major challenge for the effective use of therapeutics and agents mediating this targeting are strongly demanded. We report here on an in vivo selection technology that enables the de novo identification of pegylated DNA aptamers pursuing tissue sites harbouring a hormone refractory prostate tumour. To this end, two libraries, one of which bearing an 11 kDa polyethylene glycol (PEG) modification, were used in an orthotopic xenograft prostate tumour mouse model for the selection process. Next-generation sequencing revealed an in vivo enriched pegylated but not a naïve DNA aptamer recognising prostate cancer tissue implanted either subcutaneous or orthotopically in mice. This aptamer represents a valuable and cost-effective tool for the development of targeted therapies for prostate cancer. The described selection strategy and its analysis is not limited to prostate cancer but will be adaptable to various tissues, tumours, and metastases. This opens the path towards DNA aptamers being experimentally and clinically engaged as molecules for developing targeted therapy strategies.
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Affiliation(s)
- Laia Civit
- Chemical Biology and Chemical Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany
| | - Ioanna Theodorou
- CEA, DRT, Institut de biologie François-Jacob, Molecular Imaging Research Center (MIRCen), UMR CNRS 9199, 18 Route du Panorama, 92260, Roses, France
| | - Franziska Frey
- Chemical Biology and Chemical Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany
| | - Holger Weber
- KTB Tumorforschungsgesellschaft mbH, Research Division ProQinase, Breisacher Str. 117, 79106, Freiburg, Germany.,ProQinase GmbH, Breisacher Straße 117, 79106, Freiburg, Germany
| | - Andreas Lingnau
- KTB Tumorforschungsgesellschaft mbH, Research Division ProQinase, Breisacher Str. 117, 79106, Freiburg, Germany.,Genmab B.V., Yalelaan 60, 3584 CM, Utrecht, The Netherlands
| | - Carsten Gröber
- AptaIT GmbH, Am Klopferspitz 19a, 82152, Planegg, Martinsried, Germany
| | - Michael Blank
- AptaIT GmbH, Am Klopferspitz 19a, 82152, Planegg, Martinsried, Germany
| | - Chloé Dambrune
- CEA, DRT, Institut de biologie François-Jacob, Molecular Imaging Research Center (MIRCen), UMR CNRS 9199, 18 Route du Panorama, 92260, Roses, France
| | - James Stunden
- Institute of Innate Immunity, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - Marc Beyer
- Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115, Bonn, Germany.,Platform for Single Cell Genomics and Epigenomics at the DZNE and the University of Bonn, Sigmund-Freud-Str. 27, 53127, Bonn, Germany.,Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 27, 53127, Bonn, Germany
| | - Joachim Schultze
- Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115, Bonn, Germany.,Platform for Single Cell Genomics and Epigenomics at the DZNE and the University of Bonn, Sigmund-Freud-Str. 27, 53127, Bonn, Germany
| | - Eicke Latz
- Institute of Innate Immunity, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - Frédéric Ducongé
- CEA, DRT, Institut de biologie François-Jacob, Molecular Imaging Research Center (MIRCen), UMR CNRS 9199, 18 Route du Panorama, 92260, Roses, France
| | - Michael H G Kubbutat
- KTB Tumorforschungsgesellschaft mbH, Research Division ProQinase, Breisacher Str. 117, 79106, Freiburg, Germany.,ProQinase GmbH, Breisacher Straße 117, 79106, Freiburg, Germany
| | - Günter Mayer
- Chemical Biology and Chemical Genetics, Life and Medical Sciences (LIMES) Institute, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany. .,Center of Aptamer Research and Development (CARD), University of Bonn, Gerhard-Domagk Str. 1, 53121, Bonn, Germany.
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12
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Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy 2017; 46:907-22. [PMID: 27196817 DOI: 10.1111/cea.12760] [Citation(s) in RCA: 249] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 05/10/2016] [Accepted: 05/14/2016] [Indexed: 01/29/2023]
Abstract
Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management.
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Affiliation(s)
- E Wenande
- Danish Anaesthesia Allergy Centre, Allergy Clinic, Copenhagen University Hospital Gentofte, Hellerup, Denmark
| | - L H Garvey
- Danish Anaesthesia Allergy Centre, Allergy Clinic, Copenhagen University Hospital Gentofte, Hellerup, Denmark
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Hoshi S, Okamoto F, Arai M, Hirose T, Fukuda S, Sugiura Y, Oshika T. Polyethylene Glycol-Based Synthetic Hydrogel Sealant for Closing Vitrectomy Wounds: An In Vivo and Histological Study. Transl Vis Sci Technol 2016; 5:7. [PMID: 27226931 PMCID: PMC4874449 DOI: 10.1167/tvst.5.3.7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 04/03/2016] [Indexed: 11/25/2022] Open
Abstract
Purpose We conducted an in vivo study using Dutch pigmented rabbit eyes to test the usefulness of polyethylene glycol (PEG) sealant for the closure of sutureless sclerotomies in microincisional vitrectomy surgery (MIVS). Methods Three-port, 23-gauge vitrectomy was performed on rabbit eyes. After air leakage was confirmed by the application of 0.625% povidone–iodine at the sclerotomy site, PEG sealant was subconjunctivally injected using a 27-gauge needle through conjunctival incisions to cover the sclerotomy wounds, following which it was polymerized by the application of xenon light for 60 seconds. Ophthalmological examinations and intraocular pressure measurements were conducted the day before and 1, 3, 5, and 7 days after surgery. The eyes were enucleated for histological evaluation 7 days after surgery. Results PEG sealant was rapidly polymerized by the application of xenon light after subconjunctival injection, and it firmly sealed the sclerotomies without air leakage, as confirmed by povidone–iodine dropping, in all cases. Conjunctival and scleral wounds closed with PEG sealant were successfully attached and remained intact till the end of the follow-up period. There was no sign of postoperative hypotony or infection in any eye, and no adverse effects of PEG sealant were found. In histological examination, linear scar formation and eosinophilic staining of collagen fibers were observed at the sclerotomy sites, while the sclerotomy tunnels appeared tightly closed. Conclusions PEG sealant can be useful for the closure of sutureless 23-gauge vitrectomy incisions in rabbits. Translational Relevance The PEG sealant may become an effective option for closing vitrectomy incisions including pediatric cases.
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Affiliation(s)
- Sujin Hoshi
- Department of Ophthalmology Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Fumiki Okamoto
- Department of Ophthalmology Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Mikki Arai
- Arai Eye Clinic, Fukuoka, Japan ; The Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA
| | - Tatsuo Hirose
- The Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA ; Boston Eye Group, Brookline, MA, USA
| | - Shinichi Fukuda
- Department of Ophthalmology Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Yoshimi Sugiura
- Department of Ophthalmology Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Tetsuro Oshika
- Department of Ophthalmology Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
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Jakubovic BD, Saperia C, Sussman GL. Anaphylaxis following a transvaginal ultrasound. Allergy Asthma Clin Immunol 2016; 12:3. [PMID: 26807134 PMCID: PMC4722759 DOI: 10.1186/s13223-015-0106-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Accepted: 12/10/2015] [Indexed: 11/24/2022] Open
Abstract
Polyethylene glycol is a ubiquitous, water-soluble, organic compound found in a wide variety of commercially available products. While generally a benign substance, in rare instances, it can induce hypersensitivity reactions. Herein, we describe a case of anaphylaxis to polyethylene glycol-containing lubricating gel used for a transvaginal ultrasound. This case highlights the importance of early recognition of a rare cause of anaphylaxis that may occur in the health-care setting. It is of particular importance given the widespread use of similar lubricating materials in multiple practice settings for the use of internal examinations and ultrasonography.
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Affiliation(s)
- Baruch D Jakubovic
- Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue-D416, Toronto, ON M4N 3M5 Canada
| | - Corey Saperia
- Division of Allergy and Immunology, Department of Medicine, St. Michael's Hospital, Toronto, ON Canada
| | - Gordon L Sussman
- Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue-D416, Toronto, ON M4N 3M5 Canada ; Division of Allergy and Immunology, Department of Medicine, St. Michael's Hospital, Toronto, ON Canada
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