Intramuscular injection | EPFL Graph Search

Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption than subcutaneous or intradermal injections. Medication administered via intramuscular injection is not subject to the first-pass metabolism effect which affects oral medications. Common sites for intramuscular injections include the deltoid muscle of the upper arm and the gluteal muscle of the buttock. In infants, the vastus lateralis muscle of the thigh is commonly used. The injection site must be cleaned before administering the injection, and the injection is then administered in a fast, darting motion to decrease the discomfort to the individual. The volume to be injected in the muscle is usually limited to 2–5 milliliters, depending on injection s

Capacitive sensor to monitor the level of drug inside an injector pen

Sylvain Paul Fernand Joly

Diabete is a disease which is spreading faster than ever, impacting now a larger population. Patients suffering from this disease need the injection of insulin to control extracellular sugar levels. Pharmaceutical companies developed injector pens to allow patients to inject themself the right amount of drug. But the dosage depends on many parameters as the previous meal, current blood sugar level... and a wrong dosage can lead to health problem e.g., loss of conciousness at short terms and severe diseases like cardiac pathologies at long terms... To prevent these situations, a smart pen cap has been developed at Valtronic Technologies to follow and log the individual injections by measuring the level of drug in the pen, the temperature, and the relative humidity to allow the patient and the medical staff to have an history of the injections and the climatic conditions.Injector pen and smart pen cap have been firstly presented with a non-exhaustive list of different physics which can be used to measure a level of liquid. For need of precision, the capacitance technique is the best technology choice. Therefore, the smart pen cap is based on a capacitive sensor. Different capacitance converter topologies have been compared through a bibliographic study. It appears that the Lock-in converter gives the best sensitivity and Charge Sensitivity Amplifier has the lowest power consumption. A trade-of was to use a capacitance-to-digital-converter. A chip from Analog device has been selected due to its high resolution below the femto-farad level, its simple interface and its availability on the market which allows a fast development and industrialisation. Then, switch and electronic structure are presented. First tests with an empty device have been conducted to find the noise floor, which is below 0.1fF.Subsequently, a study of different electrodes configuration has been performed. Firstly, an analysis on two parallel flat electrodes has been conducted using theoretical and simulation approaches. Then, two semi-cylindrical electrodes have been analysed. A comparison has been made between two theoretical methods which are: considering an infinite number of parallel flat electrodes following the shape of the semi-cylindrical electrodes and the conformal mapping methods. This last method gives coherent results when comparing real measurements and simulation. The device is equipped with semi-cylindrical electrodes which allow for a small package and a good correlation between capacitance and drug level with a convertion slope of 0.5fF/µL. Tests have been performed which give an error of +-1 IU and +-4 IU for large injection (set point equal to 72 IU).Finally, the study of some parasitic effects is presented in the last section. An important effect is the climatic effect which affects the capacitance due to variation of electric permittivity linked to temperature change and water absorption of certain materials as plastics. To compensate for this effect, reference electrodes and a climatic sensor have been implemented. Another important effect comes from the cartridge position in the non-uniform electric field of the smart pen cap. A four electrodes device has been realized to allow a perpendicular rotation of the electric field to obtain a more constant averaged electric field. As a consequence, the position impact of the cartridge has been reduced. Other effects have been considered. The device can detect a minimum injection of 52uL.

EPFL2021

A new non-toxic chemically cross-linked ELP hydrogel for in situ protein delivery

Karine Ciapala

Proteins play an essential role in all biological processes and have been attracting more and more attention as drug candidates due to their high specificity and activity. However, their use as therapeutics has been seriously held back given that their ability to be effectively and conveniently delivered is problematic. Indeed, simple oral administration is ineffective since proteins are degraded in the digestive tract. Until now, these therapeutic agents were delivered by infusions or frequent injections. But this causes serious problems, as the compound does not get delivered in a prolonged continuous manner. Additionally, injections are also problematic as patients are reluctant to use needles unless there illness is life threatening. That is why focus has grown over the last years on developing novel delivery systems for proteins. Amongst the various types of delivery systems that exist, hydrogel based ones are very promising, as they possess remarkable biomimetic properties. The hydrogels that are chemically cross-linked are stronger than their counterparts, the physical hydrogels. An appealing approach to protein delivery that is more and more sought is to form the hydrogel in situ from an injected aqueous polymer solution and to use the formed gel as a depot for the sustained release of the protein. Oxygen sensitive gellation is an interesting stimulus to form these gels, but has not been successfully developed, as the gelling kinetics are too slow. Therefore, research groups have turned to the use of toxic chemicals to speed up the reaction. Elastin-like poylpeptides (ELP) are artificial biopolymers that are composed of a pentapeptide repeat. This repeat consists of Val-Pro-Gly-Xaa-Gly, where Xaa denotes a guest residue. An interesting characteristic of ELPs is that they are thermally responsive. Meaning, that when in solution they go through a lower critical solution temperature (LCST) transition. Below their LCST they are soluble in water and above their LCST they are insoluble. ELPs are well suited for drug delivery applications for many reasons such as their biocompatibility. The ELP that is studied is ELP9 Gel. Its guest residues are Val, Ala and Cys in a ratio of 1:14:1 respectively. As this ELP has cysteines it has the capacity to form a gel via cross-linking of the thiols groups by oxidation. The rheological tests that were carried out showed that this ELP9 Gel has all the characteristics of a gel. Furthermore, its gelling kinetics were greatly increased by heating it, but still remain too long for in situ applications. This suggests that the LCST behaviour of ELPs seems to play some role in favouring the cross-linking. But further controls remain to be done to confirm this hypothesized tandem process. A delivery strategy that involved this ELP9 Gel and Blue Fluorescent Proteins (BFP) with added cysteines was not successful as the molecular biology to obtain the modified proteins failed. However, the elaboration of a fusion peptide between Glucagon-Like-Peptide-1 (GLP-1) and ELP9 Gel was accomplished. The preliminary activity assay showed a reduced activity in comparison to the GLP-1 peptide alone. Unfortunately this ELP9 Gel has a setback due to its slow gelling time. Therefore, before continuing the research on the delivery strategies, it would be wiser to create a better ELP. If a new ELP with a higher cysteine concentration and lower transition temperature can be created, its gelling kinetics may be favourable for in situ protein delivery applications and thus, a chemically cross-linked hydrogel that does not require any toxic cross-linker would be available. This would be a big step in creating a very robust hydrogel for protein delivery applications but also for tissue regeneration

2009

Protein engineering approaches for direct antigen targeting in CD8+ T cell inducing vaccines

Vasiliki Panagiotou

Effective vaccine design and public vaccination programs have led to the eradication of several diseases and protected millions of people from deadly infections. However, intracellular infections remain a challenge and their eradication requires the activation of cytolytic mechanisms. CD8+ T cells promote effector mechanisms for infected cell killing subsequent to their priming by antigen-presenting cells. Their activation occurs upon detection of intracellular antigen in a pathway that many current subunit vaccine technologies are trying to approach by cross-presentation. Advances in CD8+ T cell-inducing subunit vaccines include direct targeting of antigens to cross-presenting cells and are studied in this thesis. Antigen delivery to the appropriate cell type for cross-presentation to CD8+ T cells can occur with fusion antibodies. Our laboratory has previously demonstrated that antigens bearing an erythrocyte-binding antibody domain (TER119) target the liver. We used this technology to fuse TER119 and ovalbumin (OVA) antigen with the BBOX domain of the high mobility group box 1 (HMGB1) danger signal and co-administer it with CpG-B adjuvant in a hepatic vaccine context. In liver vaccines, activation of local cytotoxic responses represents an important challenge. Erythrocyte-mediated OVA delivery with adjuvants resulted in cytotoxic CD8+ T lymphocyte (CTL) activation with memory formation in the liver and protection was provided after infection with Listeria monocytogenes. Another method for antigen targeting is through a cross-presenting dendritic cell (DC) subset, called CD8+ DCs. Recent studies in mice showed successful vaccination against OVA fused to XCL1 ligand, which binds CD8+ DCs. To attract CD8+ DCs to the site of injection for increased antigen uptake, we co-injected XCL1-OVA with a fusion protein consisting of XCL1 and the extracellular matrix (ECM) binding domain of placenta growth factor-2 (PlGF-2123-144), called XCL1-PlGF. XCL1-PlGF binds extracellular matrix at the injection site and attracts CD8+ DCs locally. In the context of prophylactic and therapeutic vaccination, the combination of two fusion proteins (XCL1-OVA and XCL1-PlGF) enhanced cytotoxicity and prolonged survival against B16-OVA melanoma. Finally, antigen transport via biomaterial delivery platforms was evaluated as an alternative method to deliver antigens to immunologically relevant sites. Our laboratory and others have shown that nanoscale carriers promote CTL responses in vaccination. Here we present a cationic micelle vaccination platform in which OVA and adjuvant (CpG-B and/or MPLA) loading is mediated by non-covalent molecular encapsulation and adsorption. Following a prime and double boost vaccination, CTL responses were raised in the spleen and lymph nodes of vaccinated mice, along with antigen-specific antibody production. These findings highlight the advantages of the micelle carrier platform in vaccine applications. Overall, this thesis presents novel techniques to target antigens to the appropriate cell compartments, facilitating CTL activation in vaccination either by direct targeting of antigen fused to antibodies and chemokines, or antigen delivery with polymeric vehicles. These platforms for optimized delivery seek to improve current approaches and impact the design of new strategies in CD8+ T cell inductive vaccination.

EPFL2016