The results of this IP injection were the disappearance of the ascites associated with the rupture. Two early reports aroused the global interests of stem cell transplantation in IBD management. PubMed Because of the injection of cannabis, the patient was predicted to have some level of THC in the blood from absorption. After intraperitoneal injection of macrophages labeled with [3 H]cholesterol, the tracer can be detected in the plasma, liver, . Thus, IP and AI routes are free of pulmonary embolism issue. Of the time points we tested (6, 16, 24 h) our results showed that a 16-h post-intraperitoneal injection image scan provided the best contrast in mice regardless of age or disease burden. 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. Several medications such as antibiotics are given via the intraperitoneal (IP) route in PD patients to treat episodes of peritonitis. Kean, T. J., Lin, P., Caplan, A. I. We next compared serum TSG-6 level in three administration routes at 48h and 72h respectively after MSCs transplantation using ELISA (Fig. In their study, PKH26 (a yellow-orange fluorescent dye) labeled PCs were injected intraperitoneally into healthy rat. Intraperitoneal Route of Drug Administration: Should it Be Used in Intraperitoneal injections are the preferred method of administration in many experimental studies due to the quick onset of effects post injection. A simple dengue vaccine evaluation system was established using a model of dengue type 2 virus (DENV2) infection in immunocompetent mice. This case presents the question of how THC is absorbed in the peritoneal cavity. In general, it is preferred when large amounts of blood replacement fluids are needed or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection. One study attempted to diagnose hepatic hydrothorax with the use of injecting Sonazoid intraperitoneally. While the DiR labeled cells showed very different cell distribution. Frontiers | Efficacy of intratympanic or postauricular subperiosteal PubMed Central injections. Collagen Deposition was assessed with phosphomolibidic acid-picrosirius red staining. Humans Injections, Intraperitoneal Peritoneal Cavity* / blood supply Peritoneal Neoplasms / drug therapy Peritonitis / drug therapy Substances Anti-Bacterial Agents Antineoplastic Agents . 107vs. 109 ; Fig. Second concerning is about the cell dose. One example is using ultrasound-navigation for puncture. Bookshelf Their findings showed that intraperitoneally injected MSCs would form aggregates with macrophages and lymphocytes in peritoneal cavity and remotely secreted TSG-6. It was determined that IP injections are a good option for Fenestra to quantify liver tumors in mice. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. These cells were confirmed as bone marrow MSCs using flow-cytometric analysis and differential identification (Supplementary Figures S1 and S2). Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain IP, intraperitoneal injection; IV, intravenous injection; AI anal injection; n=68 for treatment group, n=3 for DSS control. Influence of Aggregation and Route of Injection on the - PLOS When searching "intraperitoneal injections" a majority of the results relate to the use of IP injections in murine or rat models in order to study the effect of some drug or chemical. In our study, we tracked the GFP+ MSCs colon colonization, but our results also showed the short stay of MSCs after injection. Cancer Biother Radiopharm 28, 335342, doi: 10.1089/cbr.2012.1351 (2013). Depletion of O6-alkylguanine-DNA alkyltransferase activity in mammalian One study utilized IP injections to study pain in the abdomen after a hysterectomy when administering anesthetic continuously vs patient-controlled. 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. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. [7] In 1969, errors depending on a variety of techniques of administering IP injections were analyzed, and a 12% error in placement was found when using a one-man procedure versus a 1.2% error when using a two-man procedure. Federal government websites often end in .gov or .mil. Drug Deliv. PDF Chris Quigley Essentials Full Spectrum Curriculum (2023) Appendix E: Common Vehicles for Nonclinical Evaluation of Therapeutic Intraperitoneal Injection Is Not a Suitable Administration Route for Ray, A. 5C). For this reason, more MSCs aggregates would form for IP route and produce higher level of serum TSG-6 under TNF- activation, which help reducing the colon inflammation. Inflammatory bowel diseases (IBD) is a broad term that involves chronic inflammation of all or part of the gastrointestinal tract. B.X. 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. Google Scholar. (B) Quantification of FoxP3+ cells, the IP>IA and IV>DSS control, n=6 mice/group; n=3 for the control group. Establishing a xenograft mouse model of peritoneal dissemination of Comparison of colonic proliferation 7 days after MSCs injection. Not only in animal studies, some clinical trials using MSCs to treat osteogensis imperfect (OI) in GvHD, also showed less than 1% cell were detected in target organ18,19,20. A disadvantage of using intraperitoneal injections is that they can have a large variability in effectiveness and misinjection. During the observation, the body weight changes and fecal blood and their survival date was faithfully record. Mice were made diabetic by intraperitoneal injection of streptozotocin, which led to a 2- to 2.5-fold increase in plasma glucose. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. Cochrane Database Syst Rev. Language links are at the top of the page across from the title. In this study, the therapeutic efficiency of three different MSCs delivery routes (IP, AI and IV) were compared on DSS-induced colitis mouse model. In addition, even MSCs could formed aggregates in those harsh conditions, there still be a highly risk of self-removal. Certainly, cells are not microsphere which is structural rigid, they are well acknowledged about their deformation, however, a plenty of experimental data support that a substantial amount of MSCs are entrapped in the lung when following IV route16. Intraperitoneal Injection of Oncolytic Viruses H101 for Patients With Makhija, S. et al. On the contrary, the most significant advantage of IP and AI routes is that cells do not immediately enter to the blood flow, allowing sufficient blood dilution. PubMedGoogle Scholar. After 3 passages, spindle-shaped cell colonies gradually predominate in the cultures. IHC was performed according to the standard procedures. [10] The results depicted that ketobemidone consumption was significantly lower when patients controlled anesthetic through IP. 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. Epub 2010 Mar 3. Journal of molecular neuroscience: MN 44, 178185, doi: 10.1007/s12031-010-9446-6 (2011). iQ SYBR Green Supermix and CFX96 (Bio-Rad) were used for template amplification with a primer for each of the transcripts examined. PubMed Central GAPDH mRNA was used as an internal control to normalize mRNA expression. Patients should be anesthetized. A Simple Mouse Model for the Study of Human Immunodeficiency Virus The bilateral femurs and tibias were aseptically excised, stripped of connective tissues and then stored in PBS. The data showed that the TSG-6 levels increased with time in both IP and IV injection groups, while in DSS control group, the TSG-6 level decreased from 48h to 72h. Although there is no significant difference among three injection groups at 48h after MSCs transplantation, the serum TSG-6 was significant higher in IP injection group compared with naive group (P=0.024). Thus, the aim of the current study was to find out the potential safety range of medical use. In the meanwhile, the colonic homogenates were collected and colonic IL-10, TNF- were measured by ELISA assays. Obermeier, F. et al. Quantitative data are presented as the meanSD. Horwitz, E. M. et al. 6A). Google Scholar. On the contrary, the IP and AI groups showed more engraftment cells at the inflamed colon but showed fewer trapped cells in lung, liver and spleen (Fig. Gynecol Oncol 81, 7781, doi: 10.1006/gyno.2000.6108 (2001). Very few reports pay attention to factors applied in the clinic, such as injection or exposure routes, which has highly impact on stem cell therapeutic efficiency for IBD12. A simple method for evaluating dengue vaccine - ScienceDirect Khalil, P. N. et al. A consensus report written on behalf of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). Centers for Disease Control and Prevention. IP injection showed better amelioration of colitis and may be an ideal delivery way for MSCs in IBD therapy. Models should begin with local tissue infection, so that bacterial . PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Histopathological comparison of colitis after 3 days MSCs delivery. Intraperitoneal (IP) Technique The dose is 3 ml/4.5 kg (10 lbs) of euthanasia solution. Three days after MSCs transplatation, the mice were sacrificed for histological evaluation (H&E and phosphomolibidic acid-picrosirius red staining). 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. Available at: http://www.cdc.gov/ibd/ (Accessed: 7th April 2016) (2014). PubMed Central Best way for mesenchymal stem cells transplantation for colitis. Stem Cells 29, 15721579, doi: 10.1002/stem.708 (2011). Haematologica 93, 14571465, doi: 10.3324/haematol.12553 (2008). More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. Blood 122, e23e32, doi: 10.1182/blood-2013-04-495119 (2013). Peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses 320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin and tazobactam at . Intraperitoneal injection of a substance in the mouse. [13] The patient was a 51-year-old male who was hospitalized. found MSCs improved cardiac function by a remote way46. In IV group, most of MSCs were trapped in the lung, liver and spleen, while the cell that immigrated to the colon was not too much. WO2023056606A1 - Valproate (vpa) compounds for use in treating The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). In addition, IP showed more intense Ki-67 stain in bottom of the crypt, which suggested more active mucosa repair proliferation (Fig. DailyMed - PIPERACILLIN AND TAZOBACTAM injection, powder, lyophilized Admittedly, there may be an overlook of MSCs existence due to the tissue selection of frozen section and sensitivity of fluorescence imaging, the therapeutic differentiation of MSCs in our study were not clearly observed. After intraperitoneal injections, 30% of the female mice died, compared with 3% of the male. Injection of substances into peritoneum (body cavity), Current Drugs Delivered Intraperitoneally, "Why i.p. 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. The .gov means its official. Ballinger AE, Palmer SC, Wiggins KJ, Craig JC, Johnson DW, Cross NB, Strippoli GF. A modified human recombinant type 5 adenovirus . MPO activity per gram of wet tissue was calculated as: MPO activity (U/g wet tissue)=(A450) (13.5)/tissue weight (g). 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. Furthermore, the corresponding mesentery lymph nodes (MLNs) also showed relatively high MSCs existence (Fig. The serum concentration of TNFinduced protein 6 (TSG-6) was measured in DSS colitic mice at 48 and 72hours after different routes of MSCs administrations. Mice are usu (A) The colonic mRNA expression of TNF- and IL-10 was analyzed by RT-PCR; (B) cytokine contents in colonic protein extracts were determined by ELISA; n=6 mice/group; n=3 for the control group (C) Serum TSG-6 level in different groups measured by ELISA. MSCs induced more Ki-67 positive cells in the lower part of the crypt than the DSS control. These early uses of Intraperitoneal injections provide good examples of how the delivery method can be used, and provides a base for future studies on how to properly inject mice for research. In this study, we compared therapeutic efficacy of three MSCs administration routes in DSS-induced colitis. These time-tested therapies may perform well on some patients, but also exhibit inadequacies in efficacy. Injections, also known as shots, deliver liquid medications, fluids, or nutrients directly into a person's body. Intraperitoneal Injection - an overview | ScienceDirect Topics But how these miracle cells reach to the lumen and by which possible migration route? IP showed better colitis recovery and might be the optimum MSCs delivery route for the treatment of DSS-induced colitis. Six leukemia patients with Crohns disease treated with allogeneic marrow transplantation and four of five patients remained CD free 6 to 15 years after transplantation10. Ko, I. K. et al. Bethesda, MD 20894, Web Policies adult mice at 8-10 weeks of age were first anaesthetized by intraperitoneal injection of 20 mg/ml Avertin (Sigma-Aldrich) (15 l/g . For some severe cases, IBD may lead to the life-threaten complications5. It also shows how easily substances are absorbed through the peritoneal cavity after an IP injection. Li, C. Y. et al. seem to have found the key drug of MSCs in the treatment of colitis, TSG-647. Horizontal bars represent medians, boxes represent the 25th and 75th percentiles. The incidence and impact of IBD is increasing worldwide. Tyndall, A. & Ramesh, T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. At day 5, mice were randomized and injected with MSCs (1106, 200L in volume) by three delivery routes (IP, AI and IV). Google Scholar. Infiltration (I): 0, no infiltrate; 1, infiltrate around crypt basis; 2, infiltrate reaching to lamina muscularis mucosa layer; 3, extensive infiltration reaching the muscularis mucosa with abundant edema; 4, infiltration of the submucosa layer. We also evaluated serum TSG-6 in three MSCs administration route. Internet Explorer). n=3 per group. Intraperitoneal Injection Is Not a Suitable Administration Route for The AI and IV showed no significant intergroup difference, though AI had lower score (Fig. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. [citation needed]. (A) MSCs were labeled with DiR dye and given by three different ways. Twenty-five Kunming mice were exposed to Fe 3 O 4-nanoparticles via intraperitoneal injection daily for 1 week at doses of 0, 5, 10, 20, and 40 mg/kg. The histological score was defined as the sum of the two parameters (total score=E+I). Provided by the Springer Nature SharedIt content-sharing initiative. [12] This study demonstrates how intraperitoneal injections can be used to help diagnose diseases by providing direct access to the peritoneal cavity and affecting the organs in the cavity. In IP group, the MSCs existence can be detected at day 1, but gradually decreased with the time, GFP+ cells can be hardly identified in inflamed colon after day 3 (data not shown). Mice were maintained in a light/temperature-controlled room and allowed to freely access to chow diet and water. intraarticular and intraperitoneal use of opioids, pain management in the emergency room and in the intensive care unit, pain management issues during pregnancy, geriatric pain, and hospice care and end-of-life issues. Drug delivery systems for intraperitoneal therapy. gynecological and gastrointestinal cancers and has shown very promising results. National Cancer Institute. In colonic MLNs, similar results were observed, the MSCs administration induced more FoxP3+ cells accumulation than the control, but the inter-group differences were not evident (Supplementary Figure S8). PloS one 7, e33360, doi: 10.1371/journal.pone.0033360 (2012). An example of how intraperitoneal injections can be optimized is depicted in a study where IP injections are used to deliver anesthesia to mice. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. sharing sensitive information, make sure youre on a federal Though IP injection showed benefits in many human and animal studies, even recommend by National Cancer Institute (NCI) for advanced ovarian chemotherapy, it is more often applied to animals than to humans for the time being57. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. The first major problem with IV route is the pulmonary first-pass effects, which cause significant entrapment of cells15. Google Scholar. CAS Endoscopic fluorescence imaging experiments were performed at 1-h postinjection of FA-NPs, celecoxib/FA-NPs or FNC-NPs using a Karl Storz-Endoskope System. 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, . Development of Pluoronic nanoparticles of fluorocoxib A for endoscopic https://doi.org/10.1038/srep30696. local inflammation and granulomatous reactions at the site of injection, lymph node structural changes, chronic inflammation, skin ulceration, local abscess or tissue sloughing, diffuse systemic . Stem cells international 2013, 732742, doi: 10.1155/2013/732742 (2013). The study showed that the number of small droplets decreased after administration of the egg whites, indicating that they have been changed to large droplets. humans have been associated with clinical pain, inflammatory lesions, and abscess formation in . Fluorescent intensity was quantified and processed using the Living Image Software (Version 4.2; Caliper Life Science). Int J Stem Cells 1, 17 (2008). Evid Based Complement Alternat Med. Interferon-gamma (IFN-gamma)- and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Shariati M, Zhang H, Van de Sande L, Descamps B, Vanhove C, Willaert W, Ceelen W, De Smedt SC, Remaut K. Pharm Res. Study on pharmacokinetics-Study on pharmacokinetics-Innostar And the loss of MSCs in the colon may attribute to many reasons, such as, wash out, cell death, or even rejection via the innate immune system. Yui, S. et al. Generally, the FoxP3 expression was elevated in MSCs treatment (Fig. In order to compare the difference of MSCs colonization among the three delivery routes, a nontoxic NIR tracer DiR was introduced to label MSCs. In patients with peritoneal surface malignancies, perioperative IP chemotherapy has been used with good results. Zhu, H. et al. Nature medicine 5, 309313, doi: 10.1038/6529 (1999). 2019 Jun 24;36(9):126. doi: 10.1007/s11095-019-2646-z. PubMed PDF An improved mouse model of sepsis based on intraperitoneal injections Injections Intraperitoneal (IP) "Mouse" Once animal is restrained turn over so abdomen is exposed. Figure 1. 3; Supplementary Figure S6). Human peripheral blood lymphocytes (hu-PBL) can be adoptively transferred by intraperitoneal injection into mice with severe combined immunodeficiency (SCID). Upon intravenous and intraperitoneal injection of stressed MSA, fluorescent "hotspots" were observed in the spleens, livers and lungs. 2021. Then, the bone marrow was flushed out with 1mL syringe. Comparison of the Effects of Intraperitoneal Injection with Carbon