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==Early Uses==
There are few accounts of the use of intraperitoneal injections prior to 1970. One of the earliest recorded uses of IP injections involved the insemination of a guinea-pig in 1957.<ref>{{cite journal |last1=Rowlands |first1=I.W. |title=Insemination of the Guinea-pig by Intraperitoneal Injection |journal=Journal of Endocrinology |date=1957 |volume=16 |issue=1 |pages=98–106 |doi=10.1677/joe.0.0160098|pmid=13491738 }}</ref> The study however did not find an increase in conception rate when compared to mating. In that same year, a study injected egg whites intraperitoneally into rats to study changes in "droplet" fractions in kidney cells. 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.<ref>{{cite journal |last1=Straus |first1=Werner |title=Changes in "droplet" fractions from rat kidney cells after intraperitoneal injection of egg white |journal=J Biophys Biochem Cytol |date=1957 |volume=3 |issue=6 |pages=933–947 |doi=10.1083/jcb.3.6.933|pmid=13481027 |pmc=2224142 }}</ref> In 1964, a study delivered chemical agents such as acetic acid, bradykinin, and kaolin to mice intraperitoneally in order to study a "squirming" response.<ref>{{cite journal |last1=Whittle |first1=Brian A. |title=Release of a kinin by intraperitoneal injection of chemical agents in mice |journal=International Journal of Neuropharmacology |date=1964 |volume=3 |issue=4 |pages=369–IN1 |doi=10.1016/0028-3908(64)90066-8|pmid=14334868 }}</ref> In 1967, the production of amnesia was studied through an injection of physostigmine.<ref>{{cite journal |last1=Hamburg |first1=M.D. |title=Retrograde Amnesia Produced by Intraperitoneal Injection of Physostigmine |journal=Science |date=1967 |volume=156 |issue=3777 |pages=973–974 |doi=10.1126/science.156.3777.973|pmid=6067162 |bibcode=1967Sci...156..973H |s2cid=46029262 }}</ref> In 1968, melatonin was delivered to rats intraperitoneally in order to study how brain [[serotonin]] would be affected in the midbrain.<ref>{{cite journal |last1=Anton-Tay |first1=F. |last2=Chou |first2=C. |last3=Anton |first3=S. |last4=Wurtman |first4=R.J. |title=Brain Serotonin Concentration: Elevation Following Intraperitoneal Administration of Melatonin |journal=Science |date=1968 |volume=162 |issue=3850 |pages=277–278 |doi=10.1126/science.162.3850.277 |jstor=1725071|pmid=5675470 |bibcode=1968Sci...162..277A |s2cid=6484761 }}</ref> 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.<ref>{{cite journal |last1=Arioli |first1=V. |last2=Rossi |first2=E. |title=Errors Related to Different Techniques of Intraperitoneal Injection in Mice |journal=Applied Microbiology |date=1969 |volume=19 |issue=4 |pages=704–705 |doi=10.1128/am.19.4.704-705.1970|pmid=5418953 |pmc=376768 |s2cid=237231042 }}</ref>
A good example of how intraperitoneal injections work is depicted through "The distribution of salicylate in mouse tissues after intraperitoneal injection" because it includes information on how a drug can travel to the blood, liver, brain, kidney, heart, spleen, diaphragm, and skeletal muscle once it has been injected intraperitoneally.<ref>{{cite journal |last1=Sturman |first1=J A |last2=Dawkins |first2=P D |last3=McArthur |first3=N |last4=Smith |first4=M J H |title=The distribution of salicylate in mouse tissues after intraperitoneal injection |journal=Journal of Pharmacy and Pharmacology |date=1968 |volume=20 |issue=1 |pages=58–63 |doi=10.1111/j.2042-7158.1968.tb09619.x|pmid=4384147 |s2cid=41866123 }}</ref>
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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.<ref>{{cite journal |last1=Sweeney |first1=N. |last2=Marchant |first2=S. |last3=Martinez |first3=J.D. |title=Intraperitoneal injections as an alternative method for micro-CT contrast enhanced detection of murine liver tumors. |journal=BioTechniques |date=2019 |volume=66 |issue=5 |pages=214–217 |doi=10.2144/btn-2018-0162|pmid=31050302 |s2cid=143433447 }}</ref> Contrast agents were administered intraperitoneally instead of intravenously to avoid errors and challenges. It was determined that IP injections are a good option for Fenestra to quantify liver tumors in mice.
An example of how intraperitoneal injections can be optimized is depicted in a study where IP injections are used to deliver anesthesia to mice. This study goes over the dosages, adverse effects, and more of using intraperitoneal injections of anesthesia.<ref>{{cite journal |last1=Arras |first1=M. |last2=Autenried |first2=P. |last3=Rettich |first3=A. |last4=Spaeni |first4=D. |last5=Rulicke |first5=T. |title=Optimization of Intraperitoneal Injection Anesthesia in Mice: Drugs, Dosages, Adverse Effects, and Anesthesia Depth |journal=Comparative Medicine |date=2001 |volume=51 |issue=5 |pages=443–456 |pmid=11924805 |url=https://www.ingentaconnect.com/content/aalas/cm/2001/00000051/00000005/art00008}}</ref>
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.<ref>{{cite journal |last1=Dou |first1=Shuping |last2=Smith |first2=Miles |last3=Wang |first3=Yuzhen |last4=Rusckowski |first4=Mary |last5=Liu |first5=Guozheng |title=Intraperitoneal Injection Is Not Always a Suitable Alternative to Intravenous Injection for Radiotherapy |journal=Cancer Biotherapy and Radiopharmaceuticals |date=May 2013 |volume=28 |issue=4 |pages=335–342 |doi=10.1089/cbr.2012.1351|pmid=23469942 |pmc=3653381 }}</ref> It was concluded that IP administration should not be used over intravenous therapy due to high radiation absorption in the intestines. This shows an important limitation to the use of IP therapy.
The provided examples show a variety of uses for intraperitoneal injections in animals for in vitro studies. Some of the examples depict situations where IP injections are not ideal, while others prove the advantageous uses if this delivery method. Overall, many studies utilize IP injections to deliver therapeutics to lab animals due to the efficiency of the administration route.
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==Current Drugs Delivered Intraperitoneally==
Currently, there are a handful of drugs that are delivered through intraperitoneal injection for chemotherapy. They are mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed, and melphalan.<ref>{{cite journal |last1=Bree |first1=Eelco de |last2=Michelakis |first2=Dimosthenis |last3=Stamatiou |first3=Dimitris |last4=Romanos |first4=John |last5=Zoras |first5=Odysseas |title=Pharmacological principles of intraperitoneal and bidirectional chemotherapy |journal=Pleura and Peritoneum |date=1 June 2017 |volume=2 |issue=2 |pages=47–62 |doi=10.1515/pp-2017-0010|pmid=30911633 |pmc=6405033 |s2cid=79678140 }}</ref> There needs to be more research done to determine appropriate dosing and combinations of these drugs to advance intraperitoneal drug delivery.
==References==
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