Vaccine Adjuvants in Immunotoxicology
Mesut Karahan in Synthetic Peptide Vaccine Models, 2021
The most important side effect of aluminum-derived adjuvants is the formation of local granulomas at the injection site. This situation develops especially when an intradermal or subcutaneous injection is administered instead of intramuscular. Local pain, inflammation, swelling, ulcer, and necrosis at the injection site may also be observed (Maughan, Preston, and Williams 2015). Other important side effects are tendency to allergy and potential neurotoxicities with increased IgE production. Aluminum is usually excreted from the body through the kidneys. In kidney dysfunction, aluminum accumulates in the body. High levels of aluminum affect the brain and bone tissues in particular. Aluminum intoxication has also been associated with Alzheimer’s disease. Magnesium hydroxide (Mg(OH)2), zinc sulphate (ZnSO4), calcium phosphate (Ca3(PO4)2), and iron and zirconium salts are used as alternative mineral salts (Yurdakök and İnce 2008; Maughan, Preston, and Williams 2015).
Tuberculosis in Childhood
Peter D O Davies, Stephen B Gordon, Geraint Davies in Clinical Tuberculosis, 2014
The Mantoux test is the standard TST currently in use and involves the intradermal injection of two standardised tuberculin units of purified protein derivative solution. Subsequent induration, rather than erythema, is measured in millimetres after 48–72 hrs. In some countries with low TB incidence such as the United Kingdom, a TST is regarded as positive with induration of more than 5 mm in those without prior Bacille Calmette–Guerin (BCG) vaccination and more than 15 mm for those who have received BCG vaccination. WHO guidelines differ slightly in that a positive TST is regarded as positive with induration more than 10 mm for those without prior BCG vaccination and more than 15 mm for those with BCG vaccination history [101]. The US guidelines utilise a risk categorisation based on epidemiologic and clinical factors: more than 5 mm (close contacts, TB disease, immunosuppression), more than 10 mm (increased risk of disseminated disease or increased exposure to TB disease) and more than 15 mm (children > 4 years of age with no risk factors) [102].
Venous anatomy and pathophysiology
Helane S Fronek in The Fundamentals of Phlebology: Venous Disease for Clinicians, 2007
Tissue irritation and pain with local anesthetics is due to many factors. Most anesthetic solutions are acidic (pH 6.5), especially those containing epinephrine (pH 4.5). Neutralizing epinephrine-containing solutions to a more physiologic pH by adding 1 mL of 8.4% sodium bicarbonate to every 10 mL of anesthetic may reduce the pain of injection. Alternatively, plain solutions can be mixed with epinephrine 1:1000 and the pH of the original solution (pH 6.5) retained, or plain and epinephrine-containing solutions can be mixed to make them less acidic. Slow injection allows more time for the stretch receptors to become accustomed to the volume being injected. This may explain why intradermal injections are more painful than subcutaneous injections. Warming of the solutions has also been credited with decreased pain.
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
Another important consideration when discussing clinically approved subunit vaccines is the many routes of administration used to deliver them. Most clinically approved vaccines are delivered parenterally which includes intradermal, intramuscular (IM), intravenous, and subcutaneous. Intravenous administration for vaccines is generally not preferred given that this route requires administration by a healthcare provider which can reduce patient compliance. Intravenous vaccination also carriers the risk of causing anaphylactic shock [49]. Intradermal administration is advantageous in that it stimulates specialized immune cells in the skin such as Langerhans cells to present antigen. However, one issue with this method is limited by reliable methods of intradermal administration [50]. The subcutaneous route has the benefit of providing increased drainage to local lymph nodes. This route is also limited in that there are more local adverse reactions following immunization than with the IM route [51]. IM is the most widely used route of administration for vaccines. The IM route causes the least amount of local adverse reactions but may not be as immunogenic as the intradermal route likely due to the absence of the specialized immune cells in the skin [49].
Biopredictive tools for the development of injectable drug products
Published in Expert Opinion on Drug Delivery, 2022
Mônica Villa Nova, Kennard Gan, Matthias G. Wacker
Injectable drug products cover a wide variety of potential injection sites involving different physiologies and formulations. Most frequently, intravenous, subcutaneous, intramuscular, and intradermal injections are being used. Additionally, there are several less common injection sites including the intracranial [46], intrathecal [47–49], intra-articular [50], or intraosseous [51] route of administration. A formulation-centric approach requires the material and quality attributes of the delivery system to be considered. Most injectables are liquids with the drug being dissolved or dispersed in a vehicle. Their absorption kinetics is affected by a variety of physiological parameters responsible for the distribution of the drug after the injection. They include the vascularization and structure of the injection site as well as the access to other tissues, such as the lymphatic system [52]. Regarding the subcutaneous route of administration, the preferred injection site varies between Asian and Western countries, leading to differences in the absorption rate as well [6].
Role of the Cadaver Lab in Lymphatic Microsurgery Education: Validation of a New Training Model
Published in Journal of Investigative Surgery, 2022
Lucian P. Jiga, Corrado C. Campisi, Zaher Jandali, Melissa Ryan, Michele Maruccia, Luigino Santecchia, Mario Cherubino, Janniko Georgiadis
Intradermal injections of either 25 mg/ml PBV (Guerbet GmbH, Sulzbach, Germany) or 5 mg/ml ICG (Verdeye, Diagnostic Green GmbH, Aschheim-Dornbach, Deutschland) were performed 30 minutes before lymphatic vessel mapping and dissection in both the upper and lower limbs of each cadaver. Dissection was performed using prismatic loupe magnification and operative microscope (Zeiss, Oberkochen, Germany), surgical instruments (Aesculap, Tuttlingen, Germany) and if appropriate, supermicrosurgical instrumentation (S&T AG, Schaffhausen, Switzerland). Intradermal injections were performed in the dorsum of the hand, medial upper arm, dorsum of the foot and the medial proximal thigh respectively. To assure consistency, all injections were performed using the same protocol. A total of 0.2 ml PBV and ICG (per injection site) were performed on the dorsum of the hand. The same PBV and ICG volume was injected approximately 14 cm distal from the axilla, along the proximal third of the bicipital groove, followed by the dorsum of the foot (2 cm proximally to the 2nd interdigital space) and 20 cm distal to the mid-inguinal point toward the groin.
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