Use Of Subcutaneous Injections Research Articles

Modeling drug transport and absorption in subcutaneous injection of monoclonal antibodies: Impact of tissue deformation, devices, and physiology

The pharmaceutical industry has experienced a remarkable increase in the use of subcutaneous injection of monoclonal antibodies (mAbs), attributed mainly to its advantages in reducing healthcare-related costs and enhancing patient compliance. Despite this growth, there is a limited understanding of how tissue mechanics, physiological parameters, and different injection devices and techniques influence the transport and absorption of the drug. In this work, we propose a high-fidelity computational model to study drug transport and absorption during and after subcutaneous injection of mAbs. Our numerical model includes large-deformation mechanics, fluid flow, drug transport, and blood and lymphatic uptake. Through this computational framework, we analyze the tissue material responses, plume dynamics, and drug absorption. We analyze different devices, injection techniques, and physiological parameters such as BMI, flow rate, and injection depth. Finally, we compare our numerical results against the experimental data from the literature.

Advancements in oral insulin: A century of research and the emergence of targeted nanoparticle strategies

AbstractWith the growing prevalence of diabetes, there is an urgent demand for a user‐friendly treatment option that minimizes side effects related to the use of subcutaneous injections. Scientists have dedicated over a century to developing an oral dosage form of insulin that can be administrated orally. The oral route of administration is the most desirable route for regularly dosed drugs in terms of safety and patient compliance. However, oral delivery of insulin remains a formidable challenge due to its intrinsically limited ability to cross the intestinal epithelium membrane and susceptibility to enzymatic degradation. This article reviews oral insulin research over the past decade, with a particular focus on surface modifications of nanoparticles (NPs). Various strategies involving controlling surface charges, utilizing protective proteins, and targeting specific receptors with ligands have been explored. Notably, surface modifications of the NPs for targeting specific intestinal receptors have shown promise in enhancing insulin oral absorption and bioavailability. Advanced technologies such as oral microneedles and gene therapy have also been developed, but their safety requires further assessment. Despite encouraging preclinical results across numerous strategies, the current clinical evidence is less optimistic. In summary, the present findings highlight the substantial journey that still lies ahead before achieving successful oral delivery of insulin.Practical Applications: This review provides a summary of recent progress in oral insulin delivery, particularly highlighting surface‐modified functional nanoparticles serving as an effective drug delivery system, which offers valuable information to the researchers. Due to the limited effectiveness of oral protein drugs caused by biological barriers, innovative technologies and drug delivery systems have been developed to overcome these obstacles and achieve therapeutic goals. This review concluded that surface modifications to nanoparticles can improve insulin stability and permeability, thereby enhancing oral bioavailability. It could assist researchers in developing more effective and patient‐friendly oral drug delivery systems.

Tanning Melanotan Jabs and Nasal Spray: Safe or Not?

Cultural values among young population are focused on the concept of skin tanning as a perception of health and attractiveness. This has populated the development of using synthetic tanning agents especially with the advertisement coming from the social media. Synthetic tanning agents in forms of nasal spray or injections have gained publicity of use within society through the web and other uncontrolled sourcing routes. Warnings have been issued by UK Medicines and Healthcare products Regulatory Agency, and Irish Medicines Board against the use of subcutaneous injections labelled as Melanotan, after the upsurge in consuming tanning injections that has noticed in recent years [1].

Use of Subcutaneous Injection of Epinephrine and Triamcinolone with Tranexamic Acid Reduces Blood Loss, Transfusion Rates, and Length of Stay in Open Sagittal Craniosynostosis Repair.

In 2017, we adopted the use of triamcinolone/epinephrine (TAC/Epi) scalp injection and later added tranexamic acid (TXA) in open sagittal synostosis surgery. We believe that this reduced blood loss and transfusion rates. A total of 107 consecutive patients operated for sagittal synostosis aged <4 months from 2007 to 2019 were retrospectively reviewed. We collected demographics [age, sex, weight at surgery, and length of stay (LOS)], intraoperative information [estimated blood loss (EBL)], administration of packed red blood cell, transfusion of plasmalyte/albumen, operating time, baseline hemoglobin (Hb) and hematocrit (Hct), type of local anesthetic (1/4% bupivacaine vs. TAC/Epi), and use/volume of TXA. Hb, Hct, coagulation studies, and platelets at 2 hours postoperatively and postoperative day (POD) 1 were recorded. There were 3 groups: 1/4% bupivacaine/epinephrine (N=64), TAC/Epi (N=13), and TAC/Epi with TXA bolus/infusion intraoperatively (N=30). Groups receiving TAC/Epi or TAC/Epi with TXA had lower mean EBL ( P <0.0001), lower rate/amount of packed red blood cell transfusion ( P <0.0001), lower prothrombin time/international normalized ratio on POD 1 ( P <0.0001), higher platelets ( P <0.001), and shorter operative time ( P <0.0001). LOS was shortest for TAC/Epi with TXA ( P <0.0001). No significant differences between groups were noted on POD 1 Hb, Hct, or partial prothrombin time. Post hoc testing revealed an advantage of TAC/Epi with TXA over TAC/Epi alone for 2-hour postoperative international normalized ratio ( P =0.0249), Operating Room time ( P =0.0179), and LOS ( P =0.0049). Use of TAC/Epi alone reduced EBL, LOS, Operating Room time, and improved laboratory values postoperatively in open sagittal synostosis surgery. Addition of TXA further improved operative time and LOS. It is likely that lower rates of transfusion could be tolerated.

Subcutaneous injections: A cross-sectional study of knowledge and practice preferences of nurses

Background Widespread use of subcutaneous injection for parenteral medications is likely to be related to high medication bioavailability and rapid onset of action. Correct subcutaneous injection technique and site selection are essential for nursing care quality and patient safety. Aim The study aimed to determine nurses’ knowledge and practice preferences regarding subcutaneous injection technique and administration site selection. Design This cross-sectional study took place between March and June 2021. Methods This study included 289 nurses, willing to participate who worked in units performing subcutaneous injections in a university hospital in Turkey. Results Most nurses reported their preferred administration site for subcutaneous injections was the lateral aspects of the upper arm. More than half of the nurses did not use a rotation chart, they swabbed the skin before a subcutaneous injection, and they always pinched the skin at the injection site; 50% of nurses reported always administering subcutaneous injections at an angle of either 90 or 45 degrees. Most nurses performed an injection in less than 30 s and waited for 10 s before withdrawing the needle. They did not apply massage onto the site following the injection. Nurses’ knowledge of subcutaneous injection was at a moderate level. Conclusions Nurse knowledge of best practice subcutaneous injection administration and site selection could be improved in line with current evidence to improve personcentred and quality and safe care delivery. Future research should involve developing and evaluating educational strategies and practice standards to enhance nurse understanding of best practice evidence to meet patient safety goals.

PSY223 - QUALITATIVE RESEARCH IN HAEMOPHILIA A: EMICIZUMAB TRANSFORMS LIFESTYLE OF PATIENTS WITH INHIBITOR

Emicizumab is a monoclonal antibody developed for treatment of patients with haemophilia A (HA). Alongside clinical development program; qualitative data have been collected from patients and healthcare professionals (HCPs). Japanese HA patients with inhibitors from the emicizumab phase 1 study answered open-ended questions about their daily life while treated with emicizumab. Translation of their written answers was analyzed. Six French HCPs who had been in contact with French patients with inhibitors treated with emicizumab as part of the HAVEN 1 and 2 phase 3 studies were interviewed by phone. Specific interview guides were used, to collect information about the impact of emicizumab treatment in patients’ daily life. Interviews were exploratory, semi-structured, and lasted 1 hour. Thematic qualitative analysis on the interview transcripts and written answers of the phase 1 study was conducted. Then, a conceptual model was developed describing the experience of patients with HA treated with emicizumab. French HCPs (n=3 physicians, 2 nurses and 1 CRA) and Japanese patients (n=11) reported “spectacular” changes in patients’ daily lifestyle while treated with emicizumab. Patients reported changes they qualified significant: decrease in bleeding frequency, severity and associated joint/muscle pain. This led to improved emotional state, increased daily activities, better autonomy, and for some patients a major change in their daily lifestyle. Patients could travel further away from home thanks to treatment’s portability, ease of use of subcutaneous injection, and low frequency of injections. HCPs reported that patients were feeling more confident in the future, were able to make plans again, and treatment was so effective and convenient to use that some patients were not feeling ill anymore. Emicizumab significantly changed the way patients handled HA, and resulted in a transformation to their lifestyle. This may also have an impact on organization in HCPs’ health unit and medical practices.

Dabigatran etexilate in the treatment of localized intravascular coagulopathy associated with venous malformations

IntroductionVenous malformations (VM) are congenital slow-flow vascular malformations. A common complication is localized intravascular coagulopathy (LIC), which results from chronic, localized, intraluminal activation and consumption of clotting factors and is characterized by elevated D-dimer and, in severe cases, decreased fibrinogen levels. Therapeutic options include anti-coagulation by Low Molecular Weight Heparin (LMWH) which has been reported to improve pain, decrease thrombosis, improve laboratory parameters and reduce hemorrhagic complications. However, the use of subcutaneous injections of LMWH has several limitations and the indications for therapy remain controversial. Materials and methodsWe present the first small case series of 3 patients with VM-LIC in whom a long-term treatment by dabigatran etexilate, a direct thrombin inhibitor, was initiated in the setting of ambulatory hemostasis consultations. ResultsClinically, drug tolerance was excellent in all 3 patients. Moderate hemorrhagic complaints occurred in 2 out of 3 patients but there was no thromboembolic event under dabigatran therapy. Dabigatran provided symptomatic relief on pain, swelling and heaviness feeling. Biologically, dabigatran treatment showed various modifications in D-dimers level but the fibrinogen level and platelet count remained unchanged. ConclusionIn conclusion, dabigatran etexilate may provide a viable and more convenient alternative to LMWH in the long-term treatment of VM-LIC. The dose has to be tailored in each patient in function of the bleeding tendency and laboratory hemostasis parameters.

Formation of multimeric antibodies for self-delivery of active monomers

Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab). These Abs were examined for their ability to self-assemble and form ordered aggregates, by several biophysical methods. Atomic force microscopy analyses revealed the formation of multimeric nanostructures. The biological activity of multimeric IgG or IgY particles was retained and restored, in a dilution/time-dependent manner. IgG activity was confirmed by a binding assay using HER2 + human breast cancer cell line, SKBR3, while IgY activity was confirmed by ELISA assay using the VP2 antigen. Competition assay with native Herceptin antibodies demonstrated that the binding availability of the multimer formulation remained unaffected. Under long incubation periods, IgG multimers retained five times more activity than native IgG. In conclusion, the multimeric antibody formulations can serve as a storage depositories and sustained-release particles. These two important characteristics make this formulation promising for future novel administration protocols and altogether bring to light a different conceptual approach for the future use of therapeutic proteins as self-delivery entities rather than conjugated/encapsulated to other bio-compounds.

Effect of Hierarchical Cluster Formation on the Viscosity of Concentrated Monoclonal Antibody Formulations Studied by Neutron Scattering.

Recently, reversible cluster formation was identified as an underlying cause of anomalously large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations, which poses a major challenge to the use of subcutaneous injection for some mAbs. A fundamental understanding of the structural and dynamic origins of high viscosities in concentrated mAb solutions is thus of significant relevance to mAb applications in human health care, as well as being of scientific interest. Herein, we present a detailed investigation of an IgG1-based mAb to relate the short-time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. The combination of light scattering, small-angle neutron scattering, and neutron spin echo measurement techniques conclusively demonstrates that, upon addition of Na2SO4, these antibodies form strongly bound reversible dimers at dilute concentrations that interact with each other to form large, loosely bound, transient clusters when concentrated. This hierarchical structure formation in solution causes a significant increase in the solution viscosity.

Transient Receptor Potential Vanilloid-4 Has a Major Role in Visceral Hypersensitivity Symptoms

The transient receptor potential vanilloid-4 (TRPV4) is an osmosensitive channel that responds to mechanical stimulation. We hypothesized that TRPV4 could be important in visceral nociception and in the development of hypersensitivity. TRPV4 expression was investigated by immunohistochemistry and reverse transcription-polymerase chain reaction. Calcium signaling and patch-clamp studies were performed in dorsal root ganglia (DRG) neurons validating the use of 4alphaPDD as a selective TRPV4 agonist. The effects of TRPV4 activation on visceral nociception were evaluated in mice that received intracolonically TRPV4 agonist (4 alpha-phorbol 12,13-didecanoate [4alphaPDD]) and in TRPV4-deficient mice in which abdominal muscle contractions in response to colorectal distention (CRD) were recorded. Intervertebral injections of TRPV4 or mismatch small interfering RNA (siRNA) were used to specifically down-regulate TRPV4 expression in sensory neurons and to investigate the role of TRPV4 in basal visceral nociception or in protease-activated receptor 2 (PAR(2)) activation-induced visceral hypersensitivity. TRPV4 agonist 4alphaPDD specifically activated a cationic current and calcium influx in colonic projections of DRG neurons and caused dose-dependent visceral hypersensitivity. TRPV4-targeted but not mismatched siRNA intervertebral treatments were effective at reducing basal visceral nociception, as well as 4alphaPDD or PAR(2) agonist-induced hypersensitivity. Effects of the TRPV4 ligand were lost in TRPV4-deficient mice. 4alphaPDD selectively activates TRPV4 in sensory neurons projecting from the colon, and TRPV4 activation causes visceral hypersensitivity. TRPV4 activation is implicated in the nociceptive response to CRD in basal conditions and in PAR(2) agonist-induced hypersensitivity. These results suggest a pivotal role for TRPV4 in visceral nociception and hypersensitivity.

Mini‐dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: The Brisbane experience

To evaluate the use of small doses of glucagon using an insulin syringe in mild or impending hypoglycaemia in children with type 1 diabetes. Data were collected from patients attending the Paediatric Diabetes Clinic at the Queensland Diabetes Centre at the Mater Hospital, Brisbane in 2002-2004 following the institution of a new protocol for home management of mild or impending hypoglycaemia associated with inability or refusal to take oral carbohydrate. The protocol recommended the use of subcutaneous injections of glucagon using insulin syringes at a dose of two 'units' (20 microg) in children 2 years of age or younger, and for older children one unit per year of age up to a maximum of 15 units (150 microg), with an additional doubled dose given if the blood glucose had not increased in 20 min. Over a 2-year period, 25 children were treated with mini-dose glucagon on a total of 38 occasions. Additional doses were required for recurring hypoglycaemia on 20 (53%) occasions. The child could be managed at home on 32 (84%) of these 38 occasions, with only 6 (16%) children needing hospital treatment. Our study confirmed that small doses of glucagon given subcutaneously with an insulin syringe is a simple, practical and effective home treatment of mild or impending hypoglycaemia due to gastroenteritis or food refusal in children with type 1 diabetes.

Prevention and treatment of motor fluctuations

The symptoms of Parkinson's disease can become increasingly difficult to control as the disease advances, particularly with the development of motor complications, such as end-of-dose wearing-off and dyskinesias, following long-term therapy. At this stage, the patient is frequently referred to a Parkinson's disease specialist for advice on the management of their disease. In this review we provide an overview of the Parkinson's disease specialist's strategies for coping with such problems. This includes strategy to prevent or delay motor fluctuations and the concept of the long duration response. The paper also includes establishing the optimum and most rational levodopa treatment schedule, improving levodopa absorption, use of COMT-inhibition, the addition of oral dopaminergic agonists, and the use of subcutaneous injections or infusions of apomorphine or lisuride. Finally, we highlight the increasing importance of treatment strategies that stimulate dopamine receptors in a more continuous, less pulsatile manner as a way of reducing the risk of developing treatment-associated motor complications.

Reduced blood loss during burn surgery.

The purpose of this study was to investigate the use of subcutaneous injection of burn wounds and skin graft donor sites with an adrenaline-saline solution to reduce blood loss during burn surgery. This retrospective study reviewed the requirements of blood products in 30 randomly selected adult patients with more than 10% body area burned, who had at least one burn operation at a university regional burn center, between January 1991 and June 1997. Patients were matched by age and percent body area burned and stratified according to the surgical technique in two groups. In Group 1, 15 patients received the modified tumescent surgical technique: subcutaneous injection of adrenaline (1 part/million in warm saline solution) into the subcutaneous tissue of the donor sites for autologous skin graft and areas of burn eschar to be excised, combined with pneumatic tourniquets in extremities and saline-adrenaline soaked nonadherent pads. In Group 2, 15 patients received the traditional surgical technique: soaked gauze compresses with an adrenaline-thrombin solution (1 ml of 1:1,000 adrenaline, thrombin 10,000 units, and 1 L of normal saline). Outcome measures, transfusion of blood products, operating time and complications between the two patient groups were analyzed using the Wilcoxon 2-sample test. The two patient groups were not different by age (40.4 +/- 19.4 vs 38.9 +/- 17.9), percent total body area burned (27.6 +/- 15.4 vs 32.8 +/- 13.4), or percent full thickness burn (7.0 +/- 8.5 vs 11.5 +/- 8.5). The modified tumescent surgical technique significantly reduced mean total blood units transfused per patient (7.9 +/- 11.5 vs 15.7 +/- 12.9 units; P = .031), and the mean blood units transfused intraoperatively per patient (4.7 +/- 7.8 vs 8.9 +/- 8.0 units; P = .026). The modified tumescent surgical technique significantly reduced the intraoperative and total blood transfusion requirements in our thermally injured patients.

Strategies for treating patients with advanced Parkinson's disease with disastrous fluctuations and dyskinesias.

Patients with advanced Parkinson's disease often develop severe fluctuations and dyskinesias while receiving long-term levodopa therapy. These complications can prove increasingly difficult to control. Here we review our strategies for coping with such problems. These include establishing the best rational schedule of levodopa treatment, optimizing levodopa absorption, the use of oral dopaminergic agonists, and the use of subcutaneous injections or infusions of apomorphine or lisuride. The problems of severe dyskinesias, sleep disturbances, psychotoxicity, and urinary difficulties also are considered. Finally, the role of new surgical procedures to treat Parkinson's disease is reviewed.

Intermittent subcutaneous infusion of opioids in hospice home care: an effective, economical, manageable option.

Administration of oral opioids is not always possible for terminally-ill patients. Obstruction, emesis, or inability to swallow frequently force us to seek alternative routes of administration. When the rectal route is contraindicated, impractical, or otherwise rejected by the patient or caregivers, we must resort to the parenteral route. The purpose of this study has been to validate the effectiveness, manageability, and side effects of bolus infusions of opioids utilizing an indwelling subcutaneous butterfly needle. The retrospective chart review included a convenience sample of 50 patients enrolled in our home-based hospice program who required subcutaneous infusion of opioids at some point during their enrollment. The total number of patients served during this time was 112. In the majority of cases (88 percent), the indication was inability to swallow or difficulty swallowing, which was related to impending death. Morphine sulfate was the opiate used in 955 of the cases reviewed. The mean four-hourly dose was 14.3 mg, with a range of 5 to 60 mg. Pain ratings were recorded using a 0-10 scale, both prior to initiation of and during the use of subcutaneous injections. Of the 42 percent of patients able to indicate a pain rating (0-10 scale) all rated their pain at 2 or below while using the subcutaneous route. No objective signs of pain were noted by caregivers or hospice nurses in the 58 percent of patients who were unable to rate their pain. The mean duration of time the needle remained in place was 4.62 days, with a range of 1-26 days.(ABSTRACT TRUNCATED AT 250 WORDS)

IMMUNITY RESULTS OBTAINED WITH DIPHTHERIA TOXOID (MODIFIED TOXIN) AND ONE-TENTH L + MIXTURES OF TOXIN-ANTITOXIN IN THE PUBLIC SCHOOLS OF NEW YORK CITY (MANHATTAN AND THE BRONX)

INTRODUCTION The large and increasing use of subcutaneous injections of some form of modified toxin for purposes of active immunization, makes it important to utilize this toxin in the form in which it will produce the greatest amount of immunity, with the minimum amount of deleterious after effect. It is important to grasp that in any preparation it is the diphtheria toxin or derivatives of it, and nothing else, that immunizes. Ehrlich, in 1895, discovered that when fresh diphtheria toxin deteriorates in strength a peculiar change takes place. The toxicity for the guinea-pig drops faster than its power to neutralize antitoxin. At a certain stage in deterioration the toxin in even large doses no longer causes death in animals, but it still neutralizes a considerable percentage of its original amount of antitoxin. Thus, if the preparation drops in toxicity from 100 minimum lethal dosage to 5 minimum lethal dosage per

The Use of Subcutaneous Injections of Heroin in Cardiac Asthma

The Use of Subcutaneous Injections of Heroin in Cardiac Asthma

I. Donath. Treatment of progressive paralysis with nucleic acid injections. Die Behandlung der progressiven algemeinen Paralyse mittels Nukleinsaüire—Injectionen. Algem. Zeitschr. fur Psychiatry. bd. LXVI, S. 421, 1910

Based on the assumption that toxic metabolic products play an important role in the origin of many of the symptoms observed during progressive paralysis, Donath in 1903 proposed the use of subcutaneous injections of saline saline in the treatment of progressive paralysis. The results obtained turned out to be very favorable and led the author to the idea of using not a simple saline solution, the action of which is limited to the fact that it helps to remove harmful metabolic products from the body, but to find some substance that, by enhancing the oxidation processes, would make it possible to destroy those in blood toxins. Kochovsky tuberculin, proposed for this purpose by Pilcz, has the disadvantage that injections can lead to an exacerbation of a torpid tuberculous process, the existence of which until then was not manifested in any way. As a result, the author settled on a nucleic acid, the subcutaneous injection of which results in significant leukocytosis, accompanied by an increase in temperature by 11/2-1; in some cases a more significant increase is also observed, so that the temperature can reach 40 .

PARAFFIN INJECTED SUBCUTANEOUSLY FOR THE CORRECTION OF NASAL AND OTHER DEFORMITIES.

HISTORY. To Dr. J. Leonard Corning of New York belongs the credit of first experimenting along the lines of subcutaneous injection of oils; and, although applied to an entirely different purpose to that which paraffin is now devoted, yet of much import, since it was demonstrated that sterilized oils could be used subcutaneously, without resultant inflammation. Following this same idea, directed in a different channel, Gersuny of Vienna, in 1900, published an article stating that melted vaselin, when injected into a yielding tissue, forms a small tumor which remains in situ , causing no appreciable reaction. He used this method to overcome the deformity resulting from castration, blemishes due to cavities, depressed scars, and also for narrowing orifices. Drs. Lynch and Heath appear to be the pioneers in America in the use of subcutaneous injection of paraffin for the correction of nasal deformities.