IP injections were suitable for serial imaging as well as imaging mice at multiple time points, which would be ideal for longitudinal drug treatment experiments. Clinical Announcement: Intraperitoneal chemo-therapy for ovarian cancer. We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are "retired" from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. But for the IP injection, because of more cell accumulation in the inflamed colon, less initial cells might reach minimum effective cell dose. The peritoneal micromilieu commits B cells to home to body cavities and the small intestine. It causes irritation of the eyes, skin, mucous membranes, and upper respiratory tract. Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion. 2020 Jun 3;37(6):119. doi: 10.1007/s11095-020-02818-8. To obtain PubMed Central Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. PubMed Central Factors such as peritoneal inflammation, surface area, peritoneal blood flow, time of contact, etc, influence the drug transfer. (D) Semi-quantitative fecal occult blood test on day 3. eCollection 2021. Intraperitoneal (IP) Injection (Injection of Sodium Pentobarbital . The incidence and impact of IBD is increasing worldwide. In brief, sections were dewaxed and rehydrated by xylol and acohol. [2] Intraperitoneal injections can be similar to oral administration in that hepatic metabolism could occur in both. RNA was reverse transcribed using the iScript cDNA Synthesis Kit (Bio Rad, Hercules, CA). IP injection showed better amelioration of colitis and may be an ideal delivery way for MSCs in IBD therapy. The MSCs may exert their therapeutic effects on mainly three following aspects: firstly, to differentiate and replace the damage tissue; secondly, to secrete soluble immunomodulatory bioactive molecules and establish a regenerative milieu; thirdly, cell-to-cell contact and interaction with immune cells. However, one recent published paper showed inconsistent results with ours, in which IV injection was identified better in comparison with intraperitoneal injection31. Proceedings of the National Academy of Sciences of the United States of America 99, 89328937, doi: 10.1073/pnas.132252399 (2002). The site is secure. The problem is obvious, the solution is not: numbers do matter in cardiac cell therapy! sharing sensitive information, make sure youre on a federal All experimental procedures performed were approved by Animal Welfare and Ethics Committee of the Fourth Military Medical University (FMMU), which are in accordance with the NIH guidelines. Cardiovascular research 96, 208209; discussion 210203, doi: 10.1093/cvr/cvs202 (2012). drug availability and human abuse potential; 10. compatibility with species, age, and health status; 11. In addition, MSCs showed inhibitory effects on proliferation of memory T-cells by direct cell contact52. The physiologic characteristic of the peritoneal cavity not only helps remove toxic metabolites from the body, but also provides a useful portal of entry in the body for several pharmacological agents. Humans Injections, Intraperitoneal Peritoneal Cavity* / blood supply Peritoneal Neoplasms / drug therapy Peritonitis / drug therapy Substances Anti-Bacterial Agents Antineoplastic Agents . 6A). Free DiR and healthy mice (without colitis) were served as control. Nonmyeloablative stem cell therapy enhances microcirculation and tissue regeneration in murine inflammatory bowel disease. At day 5, mice were randomized and injected with MSCs (1106, 200L in volume) by three delivery routes (IP, AI and IV). Although widely used as a means of administering substances, particularly injectable anaesthetics, this is an inherently unreliable technique, since inadvertent injection of some material into the gut, abdominal fat and subcutaneous tissues is a relatively frequent . Rodent (large / mouse) oral (intragastric), intravascular administration (tail vein injection, intraperitoneal injection, intramuscular injection and subcutaneous injection) Intragastric administration and oral taking of non-rodent (dog / monkey) solution and intravenous injection of extremities. Study showed that genetically modified MSCs to increase CXCR-4 expression will lead to an increase of MSCs migration to intestinal with radiation enteritis and then resulted in disease improvement24. This review discusses the usefulness of IP drug therapy and the factors influencing it, as well as strategies to increase the efficacy, and conclude that IP route is an alternate route to the more conventional drug delivery routes, and can be successfully used when the target is within the peritoneal cavity or adjacent tissue. IBD can be painful and persistent for life, which might decrease the quality of life. Gynecol Oncol 81, 7781, doi: 10.1006/gyno.2000.6108 (2001). (C) Percentage of body weight changes over time. Cell stem cell 4, 206216, doi: 10.1016/j.stem.2009.02.001 (2009). Therefore, the MSCs delivery should be tailored to the lesion kind and customized to the mechanism of action of MSCs. Intramuscular. Histopathological alterations in the mouse brain were detected after . In this study, intraperitoneal (IP) injection was used to mimic the human administration route. Collagen Deposition was assessed with phosphomolibidic acid-picrosirius red staining. However, whether the lymphocytes actually . These two kinds of MSCs differ in proliferation rates and differentiation capacities as well as show significant difference in cytokine secretome and chemokine receptor expression which may affect migration, engraft and even local function32,33,34,35,36. With the computer-assisted software, we calculated the density of collagen fibers (%) of all groups. From whole-body disease recovery, the amount of MSCs colons engraftment, tissue histological evaluation as well as levels of cytokines and TSG-6. 2019 Jun 24;36(9):126. doi: 10.1007/s11095-019-2646-z. Intraosseous. Intraperitoneal Injection. HHS Vulnerability Disclosure, Help Mol Ther 18, 13651372, doi: 10.1038/mt.2010.54 (2010). However, for IV injection, we and others found most mice will lead increased mortality because of potential pulmonary cell embolus when the cell dose increase to 110722. For the other inflammatory cytokines, such as IL-6, IL-1 and IFN-, the expression levels varied among the groups and IP delivery did not show evident advantages over others (Supplementary Figure S7). In order to compare the difference of MSCs colonization among the three delivery routes, a nontoxic NIR tracer DiR was introduced to label MSCs. The supernatants were diluted 1:30 with assay buffer consisting in 50mM phosphate buffer pH 6.0 with 0.167mg/mL o-dianisidine (Sigma) and 0.0005% H2O2.The colorimetric reaction was measured at 450nm between 1 and 3min in a spectrophotometer (Varioskan Flash Multimode Reader, Waltham, MA). [4] In 1964, a study delivered chemical agents such as acetic acid, bradykinin, and kaolin to mice intraperitoneally in order to study a "squirming" response. The Scheme (Fig. supply of IGF-I to adolescent and adult animals or humans is not known. -Lactalbumin is an example of a "retired" self-protein because its expression in normal . Nature protocols 5, 550560, doi: 10.1038/nprot.2009.238 (2010). Acute colitis was induced in C57BL/6 male mice by feeding 5% DSS (molecular weight 40000Da; Sigma) dissolved water for 5 days, followed by five days of regular drinking water according to our previously published study63. The fecal occult blood test on the day 3 also showed nearly complete absence of occult blood in IP group. of the needle exposed to assure 4-5mm injection depth. Intraperitoneal injections may also allow too-rapid entry of bacteria or LPS into the blood. Blonski, W., Buchner, A. M. & Lichtenstein, G. R. Treatment of ulcerative colitis. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. The IP injection showed longer colon, with mean length of 8.24cm compared with 6.90cm in AI group (P=0.0057) and 6.14cm in IV group (P<0.001; Fig. Lipids were . Quantification of collagen fiber was assessed using Image Pro Plus software (version 6.0). PloS one 7, e33360, doi: 10.1371/journal.pone.0033360 (2012). Here, we also compare the expression of FoxP3, which is frequently used to quantitate Treg cells. Blood 109, 46274634, doi: 10.1182/blood-2006-12-064345 (2007). If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. In a previous study, 14 mice were exposed to SWCNTs through intravenous (IV) injection to determine whether there were any adverse effects caused by SWCNTs on the mouse brain and also to find a safe application dosage if possible. In patients with peritoneal surface malignancies, perioperative IP chemotherapy has been used with good results. Because labeled cells are founded in Peyers patch of the gut and peripheral blood, they proposed the most likely routes might be by both lymph- and blood circulation. Another example of how intraperitoneal injections are used in studies involving rodents is the use of IP for micro-CT contrast enhanced detection of liver tumors. They found different source of MSCs with different delivery routes exhibited distinct effects on lung and cardiovascular injury. A human study showed that after injection of HDL labeled with a CE tracer, most of the tracer that was ultimately found in the bile arrived there after transfer to apoB-containing lipoproteins, . Rodents. The Journal of clinical investigation 117, 258269, doi: 10.1172/jci29159 (2007). & Dennis, J. E. MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies and Immune Modulation. Tests were read by an independent observer (Cong Liang) and scored 05 as shown by the color indicators provided by the manufacturer. Stem cell reviews 10, 127144, doi: 10.1007/s12015-013-9468-x (2014). prepared Figure 4. A study was conducted to determine the best route of administration to transplant mesenchymal stem cells for colitis. Indeed, Mariana et al. The formation of the aggregates probably limits access of the cells to the systemic circulation. Though IP injection showed benefits in many human and animal . PubMed There are few examples of the use of intraperitoneal injections in humans cited in literature because it is mainly used to study the effects of drugs in mice. [citation needed]. Google Scholar. The first major problem with IV route is the pulmonary first-pass effects, which cause significant entrapment of cells15. Augello, A., Tasso, R., Negrini, S. M., Cancedda, R. & Pennesi, G. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. To determined cytokine in colon mucosa, protein extracts were isolated by homogenization of colonic segments (50mg tissue/mL) in 50mmol/L Tris-HCl, pH 7.4, with 0.5mmol/L dithiothreitol and 10 g/mL of a cocktail of proteinase inhibitors (Sigma). In this study, the intraperitoneal injection was demonstrated as the superior way for MSCs administration in the setting of colitis amelioration. All the tissue sections in this study were scan and analyzed with Virtual slide scanning system (VS120-S, Olympus). Nature medicine 18, 618623, doi: 10.1038/nm.2695 (2012). Cell stem cell 5, 5463, doi: 10.1016/j.stem.2009.05.003 (2009). We notice that the mean density of collagen was lowest in IP group, however, IP group did not exhibit less collagen deposition than the AI group, probably due to the scatter points (Fig. Google Scholar. Intraperitoneal (ml) Footpad (ml) Mouse <0.1 . The overall therapeutic factors, MSCs migration and targeting as well as local immunomodulatory cytokines and FoxP3+ cells infiltration were analyzed. Wang, N. et al. More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. A . Overall, many studies utilize IP injections to deliver therapeutics to lab animals due to the efficiency of the administration route. Note where each injection is made and subsequent injections should be made in slightly different spot than the previous injection. Google Scholar. Growth hormone Therapeutic strategies should be based on a sound and thorough understanding of the disease mechanisms, if possible, however the causes of IBD are still unclear6. Obermeier, F. et al. Then sections were washed and blocked with normal nonimmunone goat serum for 30min. If there is negative pressure, proceed with the injection depress the plunger until the solution has been fully administered. This study goes over the dosages, adverse effects, and more of using intraperitoneal injections of anesthesia.[18]. ADS The DiR dye alone was served as control. IP injections are used for a variety of reasons: The peritoneum provides a large surface area for absorption of drug (compared with intramuscular (IM) or subcutaneous); can thus inject a larger fluid volume. Treatment for peritoneal dialysis-associated peritonitis. From two streams of research, experimental and clinical, stem cell therapy showed promising results. Our results indicated that the intraperitoneal injection is the best delivery way for MSCs, which showed better mucosa recovery and higher cell engraftment at inflamed colon. MSCs induced more Ki-67 positive cells in the lower part of the crypt than the DSS control. MPO activity per gram of wet tissue was calculated as: MPO activity (U/g wet tissue)=(A450) (13.5)/tissue weight (g). CAS Kushnir, C. L., Fleury, A. C., Silver, D. F. & Spirtos, N. M. Intraperitoneal Catheter Placement: The Hammock Technique. Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Pharm Res. Colitis showed varying degrees of alleviation after three ways of MSCs transplantation and the IP injection showed the highest survival rate of 87.5% and displayed the less weight loss and quick weight gain. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. DiR-labeled cells were injected into DSS mice by three different ways. After 5 days of DSS contained water, all the subject mice showed strong positive test of fecal occult blood. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M. & Caplan, A. I. gynecological and gastrointestinal cancers and has shown very promising results. Intraperitoneal (IP) Technique The dose is 3 ml/4.5 kg (10 lbs) of euthanasia solution. Scientific Reports (Sci Rep) Heo, J. S., Choi, Y., Kim, H. S. & Kim, H. O. volume6, Articlenumber:30696 (2016) Because it allows administering a larger volume with more radioactivity, we have investigated this route and the possibility of using it to circumvent the volume constraint we earlier experienced with pretargeting radiotherapy. Their findings showed that intraperitoneally injected MSCs would form aggregates with macrophages and lymphocytes in peritoneal cavity and remotely secreted TSG-6. Generally, the FoxP3 expression was elevated in MSCs treatment (Fig. Kyriakou, C., Rabin, N., Pizzey, A., Nathwani, A. some potent chemo and radio-labeled drugs)59. This site needs JavaScript to work properly. Essentials of Human Nutrition - Jun 13 2022 . 81421003 and No. iQ SYBR Green Supermix and CFX96 (Bio-Rad) were used for template amplification with a primer for each of the transcripts examined. After 3 passages, spindle-shaped cell colonies gradually predominate in the cultures. 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ObjectivesThis study aimed to investigate the efficacy and safety of intratympanic or postauricular subperiosteal glucocorticoid injection combined with systemic glucocorticoid in the treatment of sudden sensorineural hearing loss (SSNHL).MethodsThis study is a prospective randomized controlled study. The Journal of infectious diseases 198, 456464, doi: 10.1086/590112 (2008). [20] There needs to be more research done to determine appropriate dosing and combinations of these drugs to advance intraperitoneal drug delivery. In 1996, intraperitoneal (IP) administration of cisplatin plus intravenous (IV) cyclophosphamide proved superior to both drugs given intravenously at the same doses-which, at the time, was the standard treatment in the United States. Intraperitoneal (IP) Injection in Rats and Mice SOP Page 4 of 6 Mouse Rat 6. Such huge need of MSCs poses a cell source issue, which is a continuing technically and operationally challenge, since most of human ongoing clinical trials use significant less cell dose12. Understanding when intraperitoneal injections can be utilized and in what applications is beneficial to advance current drug delivery methods and provide avenues for further research. After centrifuge, the cells were certificated and transferred to MSC expansion culture medium consisting of a-minimum essential medium (a-MEM; Gibco, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, USA) and 100g/mL penicillin/streptomycin. Ankrum, J. Other gap junction blockers were also occasionally reported to . Drug delivery systems for intraperitoneal therapy. This shows an important limitation to the use of IP therapy. Key points to note. Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor alpha-stimulating gene-6. Condition. The measurement of inflamed colon length demonstrated therapeutic effects of MSCs injection. . The few examples that do exist pertain to the treatment of pancreatic/ovarian cancers and injections of other drugs in clinical trials. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. The histological score was defined as the sum of the two parameters (total score=E+I). The AI groups exhibited 9.5% and IV group showed 6.7% FoxP3+ cells, respectively (Fig. Briefly, colonic segments were homogenized at 50mg/mL in phosphate buffer (50mM, pH 6.0) with 0.5% hexadecyltrimethylammonium bromide. Haematologica 93, 14571465, doi: 10.3324/haematol.12553 (2008). The three groups can decrease the mortality rate compared with PBS control, however, the IP injection showed the highest survival rate of 87.5% (P=0.0021vs. Control, Fig. Human peripheral blood lymphocytes (hu-PBL) can be adoptively transferred by intraperitoneal injection into mice with severe combined immunodeficiency (SCID). The following approaches are novel, and require further testing in humans before being accepted as potential treatment options: An example of when intraperitoneal injections are not ideal is given in a study where the best route of administration was determined for cancer biotherapy. 2018 Jul;6(3):207-216. doi: 10.29252/beat-060304. . Injections are given along the midline caudal to the umbilicus or low on the right lateral abdomen. Histopathological alterations in the mouse brain were detected after SWCNTs exposure. Although controversial, intraperitoneal use in ovarian cancer has been recommended as a standard of care. Article The benefit of administering drugs intraperitoneally is the ability for the peritoneal cavity to absorb large amounts of a drug quickly. However, the therapeutic impacts of cell delivery route that is critical for clinical translation are currently poorly understood. analyzed the data, J.L. Article Side effects. In the meantime, to ensure continued support, we are displaying the site without styles Gastroenterology 114, 433440 (1998). This finding was consistent with previous published paper23, in which the intraperitoneal MSCs migrating and engraft at inflamed colon were identified by Tc-99m SPECT imaging in TNBS induced colitis. Monitor chest movements to make sure the animal is doing ok. On the mouse you want to make your IP injection in the lower right or left quadrant of abdomen trying to avoid hitting bladder, liver, or other internal organs. Figure 1. Reduced MPO activities were identified in all MSCs groups, of which IP injection showed lower MPO activity (P=0.001vs. IV and P=0.0158vs. AI; Fig. Researchers has tried many creative ways to minimize these risks. B.X. The delivery of OK-432 occurred a total of four times in a span of one week. For some chemotherapy, such as ovarian cancer, IP injection is used to attempt to localize the drug . Castelo-Branco, M. T. et al. An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry . The ELISA kit for TNFinduced protein 6 was used (CUSABIO Life science, China). Google Scholar. Available at: http://www.cdc.gov/ibd/ (Accessed: 7th April 2016) (2014). While the DiR labeled cells showed very different cell distribution. This study compared intraperitoneal injections, intravenous injections, and anal injections. Pull back on the plunger to ensure negative pressure prior to injecting. Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema. Article Overall, this section provides a few examples of the effects and uses of intraperitoneal injections in human patients.
intraperitoneal injection in humans