Administration Routes In Mice Research Articles

P-203 - Comparative in vivo PET/CT, biodistribution, and excretion study of Cu-64 labeled Polypropylene (PP) nanoplastics via various administration routes in mice

P-203 - Comparative in vivo PET/CT, biodistribution, and excretion study of Cu-64 labeled Polypropylene (PP) nanoplastics via various administration routes in mice

Δ9-tetrahydrocannabinol discrimination: Effects of route of administration in mice

BackgroundRoute of administration is an important pharmacokinetic variable in development of translationally relevant preclinical models. Humans primarily administer cannabis through smoking, vaping, and edibles. In contrast, preclinical research has historically utilized injected Δ9-tetrahydrocannabinol (THC). The present study sought to examine how route of administration affected the potency and time course of THC's discriminative stimulus properties. MethodsAdult female and male C57BL/6 mice were trained to discriminate intraperitoneal (i.p.) THC from vehicle in a drug discrimination procedure. After discrimination was acquired, a dose-effect curve was determined for i.p., oral (p.o.), subcutaneous (s.c.), and aerosolized THC. Subsequently, the time course of effects of each route of administration was determined. ResultsTHC administered i.p., p.o., s.c., or via aerosolization fully substituted for i.p. THC. The potency of THC's psychoactive effects was similar for i.p., p.o., and s.c., except that THC was more potent when administered s.c. vs p.o. in females. All routes of administration had a similar potency in both sexes. The duration of THC's psychoactive effects was similar across i.p., s.c., and p.o. routes of administration, whereas aerosolized THC produced a faster onset and shorter duration of effects compared to the other routes. ConclusionTHC administered via multiple routes of administration, including those commonly used in preclinical research (i.p. and s.c.) and more translationally relevant routes (aerosol and p.o.), produced THC-like discriminative stimulus effects in mice trained to discriminate i.p. THC. More precise predictions of THC's effects in humans may result from use of these translationally relevant routes of administration.

The 46.1 Antibody Mediates Neurotensin Uptake into the CNS and the Effects Depend on the Route of Intravenous Administration.

Central nervous system (CNS) exposure to blood-borne biotherapeutics is limited by the restrictive nature of the brain vasculature. In particular, tightly sealed endothelial cells of the blood–brain barrier (BBB) prevent the uptake of protein and gene medicines. An approach to increase the bioavailability of such therapeutics is harnessing the BBB endothelial cells’ own receptor-mediated transcytosis (RMT) mechanisms. Key to this process is a targeting ligand that can engage a BBB-resident RMT receptor. We recently identified an antibody, named 46.1, that accumulates in the mouse brain after intravenous injection. To further characterize the brain targeting and penetrating properties of clone 46.1, we conjugated neurotensin (NT) to an scFv-Fc form of the antibody (46.1-scFv-Fc-LongLinker-NT). While centrally administered NT decreases the core body temperature and locomotor activity, effects attributed to two spatially segregated brain areas, systemically administered NT has limited effects. Hence, NT can be used as a model therapeutic payload to evaluate the brain penetration of BBB-targeting antibodies and their capability to accumulate in discrete brain areas. We demonstrate that intravenously administered 46.1-scFv-Fc-LL-NT can elicit transient hypothermia and reduce drug-induced hyperlocomotion, confirming that 46.1 can deliver drug cargo to the CNS at pharmacologically relevant doses. Interestingly, when two intravenous administration routes in mice, retro-orbital and tail vein, were compared, only retro-orbital administration led to transient hypothermia. We further explored the retro-orbital route and demonstrated that the 46.1-scFv-Fc-LL-NT could enter the brain arterial blood supply directly from the retro-orbital/cavernous sinus. Taken together, the 46.1 antibody is capable of transporting drug cargo into the CNS, and at least of a portion of its CNS accumulation occurs via the cavernous sinus–arterial route.

Pharmacokinetic study of an anti-trypanosome agent with different formulations and administration routes in mice by HPLC-MS/MS.

Previously compound 12 showed great anti-trypanosome activity without toxicity in an in vivo study. In the current study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to investigate its pharmacokinetics in mouse plasma. A protein precipitation method was applied to extract the compound, and it was then separated using a Kinetex C18 column with mobile phase consisting of acetonitrile-0.1% formic acid water (50:50, v/v) at a flow rate of 300 μl/min. The analytes were detected with the multiple reaction monitoring in negative electrospray ionization source for quantitative response of the compounds. Compound 12 was detected at m/z 477.0 → 367.2, while the internal standard compound 14 was detected at m/z 499.2 → 268.2. Inter- and intra-day precision was <5.22 and 2.79% respectively, while the accuracy range was within ±9.65%. The method was successfully applied to evaluate the pharmacokinetics of compound 12 in mouse plasma with two formulations (20% Cremophor EL or sesame oil) and drug administration routes (oral and intraperitoneal injection). We observed a better drug serum concentration with the Cremophor formulation, and the two different drug administration routes did not show significant differences from the drug distribution.

Cerium Aminoclay-A Potential Hybrid Biomaterial for Anticancer Therapy.

In this study, novel biomedical properties of Ce-aminoclay (CeAC) were investigated through in vitro and in vivo assays. CeAC (≥500 μg/mL) can selectively kill cancer cells (A549, Huh-1, AGS, C33A, HCT116, and MCF-7 cells) while leaving most normal cells unharmed (WI-38 and CCD-18Co cells). Notably, it displayed a high contrast of simultaneous imaging in HeLa cells by blue photoluminescence without any fluorescence dye. Its anticancer mechanism has been fully demonstrated through apoptosis assays; herein CeAC induced high-level apoptosis (16%), which promoted the expression of proapoptotic proteins (Bax, p53, and caspase 9) in tumor cells. Besides, its biological behavior was determined through antitumor effects using intravenous and intratumoral administration routes in mice implanted with HCT116 cells. During a 40 day trial, the tumor volume and tumor weight were reduced by a maximum of 92.24 and 86.11%, respectively. The results indicate that CeAC exhibits high bioavailability and therapeutic potential based on its unique characteristics, including high antioxidant capacity and electrostatic interaction between its amino functional groups and the mucosal surface of cells. In summary, it is suggested that CeAC, with its high bioimaging contrast, can be a promising anticancer agent for future biomedical applications.

CREATING LABORATORY TECHNOLOGY OF GENERIC EPIRUBICIN PHARMECEUTICAL DOSAGE FORM

Introduction. Governments around the world seek to reduce rapidly rising health care costs. Using the same high quality and often cheaper than the original brands, generics greatly reduces costs while providing an adequate quality of care. Therefore the development of generic medicines is an important task. The purpose of the study - the reproduction of the pharmaceutical dosage form for creation of national drug-generic epirubicin. Materials and methods. The study used a substance epirubicin (Ph. Eur current edition, Teva Pharmaceutical Industries Ltd., Israel); “Farmorubicin”, production “Pfizer Italia Srl” for “Pfizer Inc.”, Italy / US and excipients conforming to with relevant regulatory documents. Mice transplanted tumor: lymphocytic leukemia P388. Methods: technological, pharmaco-analytical, biological and pharmacological. Results. Pharmaceutical analysis of reproduced generic-drug “Epirubicin-RONC®” showed that itfully meets the requirements of manufacturer’s monograph. The results of “acute” toxicity study in rats and observations of the experimental animals within 30 days after a single administration suggest that both drugs have similar toxicological properties and are almost identical. Generic “Epirubicin RONC®” and “Farmorubicin” in lyophilized dosage form for injection 10.0 mg/vial, administered once, shows equal antitumor effect at two administration routes in mice with transplantable tumor: lymphocytic leukemia P-388. Conclusion. N.N. Blokhin Russian Cancer Research Center Ministry of Health of Russia has been reproduced generic - “Epirubi-cin-RONC®”, which is fully conform to the imported drug.

Developing hyperpolarized silicon particles for in vivo MRI targeting of ovarian cancer.

Silicon-based nanoparticles are ideally suited for use as biomedical imaging agents due to their biocompatibility, biodegradability, and simple surface chemistry that facilitates drug loading and targeting. A method of hyperpolarizing silicon particles using dynamic nuclear polarization, which increases magnetic resonance imaging signals by several orders-of-magnitude through enhanced nuclear spin alignment, has recently been developed to allow silicon particles to function as contrast agents for in vivo magnetic resonance imaging. The enhanced spin polarization of silicon lasts significantly longer than other hyperpolarized agents (tens of minutes, whereas [Formula: see text] for other species at room temperature), allowing a wide range of potential applications. We report our recent characterizations of hyperpolarized silicon particles, with the ultimate goal of targeted, noninvasive, and nonradioactive molecular imaging of various cancer systems. A variety of particle sizes (20nm to [Formula: see text]) were found to have hyperpolarized relaxation times ranging from [Formula: see text] to 50min. The addition of various functional groups to the particle surface had no effect on the hyperpolarization buildup or decay rates and allowed in vivo imaging over long time scales. Additional in vivo studies examined a variety of particle administration routes in mice, including intraperitoneal injection, rectal enema, and oral gavage.

544. Comparison of AAV Serotype2 Transduction by Various Delivery Routes to the Mouse Eye

AAV gene therapy has demonstrated success for the treatment of several ocular diseases with the tropism and efficiency of AAV retinal transduction being a function of the route of administration. Subretinal injection has been the primary route to deliver AAV to the retina but this injection route carries surgical complications and transduction remains localized to the area of retinal detachment. Despite the use of suprachoroidal injections for ocular drug delivery in large animal models, this route has not been comprehensively compared to AAV vector transduction following other administration routes in mice. AAV serotype 2 (AAV2) was used to deliver a self-complementary CMV-GFP reporter cassette via intrastromal, intracameral, intravitreal, subretinal, or suprachoroidal injections. These injections were validated by fundoscopy and optical coherence tomography at the time of injection. Transduction was assessed six weeks later by fundoscopy and whole globes were evaluated for histology. Transduction of the stroma, ciliary body, retinal ganglion cells, outer retina, and retinal pigment epithelium could be seen in the various routes of delivery to the eye. In particular, the transduction of multiple retinal layers throughout the retina without the damage of retinal detachment and widespread distribution makes suprachoroidal injections a better delivery route than to subretinal injection.

Bioavailability and Brain-Targeting of Geniposide in Gardenia-Borneol Co-Compound by Different Administration Routes in Mice

Both geniposide (Ge) and borneol (Bo) are bioactive substances derived from traditional Chinese medicine. Injections containing co-compound of Gardenia-Borneol are widely used for stroke treatment in China, such as “Xingnaojing” multi-component injection. As more and more adverse reactions (especially drug allergy) were reported, it is urgent to find more effective and safer routes of administration for such kinds of medicines. In this paper, bioavailabilities and brain-target effects of geniposide in Gardenia-Borneol co-compound through different administration routes in mice were investigated. Geniposide concentrations in plasma and in brain of mice were determined by reversed-phase high-performance liquid chromatography. The pharmacokinetics parameters of intranasal (i.n.) and intragastric (i.g.) administration were compared with intravenous (i.v.) administration. The bioavailabilities of Ge were 85.38% and 28.76% for i.n. and i.g. while Tmax were 1 min and 30 min. Cmax were 21.881 ± 5.398, 1.914 ± 0.327 and 42.410 ± 6.268 μg/mL for i.n., i.g. and i.v., respectively. The AUC of Ge in brain were 32413.6 ± 4573.9, 6440.1 ± 863.7 and 37270.5 ± 4160.6 ng/g·min for i.n., i.g. and i.v., respectively. The drug target indexes (DTI) were 1.02 and 0.60 for i.n. and i.g. The results demonstrated that geniposide could be absorbed promptly and thoroughly by i.n. administration in mice and basically transported into the brain though blood vessel passways.

Manual Restraint and Common Compound Administration Routes in Mice and Rats

Being able to safely and effectively restrain mice and rats is an important part of conducting research. Working confidently and humanely with mice and rats requires a basic competency in handling and restraint methods. This article will present the basic principles required to safely handle animals. One-handed, two-handed, and restraint with specially designed restraint objects will be illustrated. Often, another part of the research or testing use of animals is the effective administration of compounds to mice and rats. Although there are a large number of possible administration routes (limited only by the size and organs of the animal), most are not used regularly in research. This video will illustrate several of the more common routes, including intravenous, intramuscular, subcutaneous, and oral gavage. The goal of this article is to expose a viewer unfamiliar with these techniques to basic restraint and substance administration routes. This video does not replace required hands-on training at your facility, but is meant to augment and supplement that training.

Manual Restraint and Common Compound Administration Routes in Mice and Rats

Being able to safely and effectively restrain mice and rats is an important part of conducting research. Working confidently and humanely with mice and rats requires a basic competency in handling and restraint methods. This article will present the basic principles required to safely handle animals. One-handed, two-handed, and restraint with specially designed restraint objects will be illustrated. Often, another part of the research or testing use of animals is the effective administration of compounds to mice and rats. Although there are a large number of possible administration routes (limited only by the size and organs of the animal), most are not used regularly in research. This video will illustrate several of the more common routes, including intravenous, intramuscular, subcutaneous, and oral gavage. The goal of this article is to expose a viewer unfamiliar with these techniques to basic restraint and substance administration routes. This video does not replace required hands-on training at your facility, but is meant to augment and supplement that training.

Antinociceptive effectiveness of triterpenes from rosemary in visceral nociception

Ethnopharmacological relevanceRosemary is a species used worldwide as a common spice, but also in folk medicine for their therapeutic properties against abdominal pain. The rationale of this study was to examine the involvement of triterpenes and to compare their effectiveness in the antinociceptive effect of an ethanol extract of Rosmarinus officinalis L. (Lamiaceae). Material and methodsFractionation and HPLC analyses allowed the identification of a mixture of micromeric (121mg/g), oleanolic (64mg/g) and ursolic (83mg/g) acids as partial antinociceptive responsible in an ethyl acetate fraction of R. officinalis by using the acetic acid-induced abdominal constrictions model in mice. ResultsThese triterpenes individually evaluated produced a significant and dose-dependent antinociceptive response with similar potency as follows: ED50=1.1mg/kg (0.9–1.3mg/kg), 2.1mg/kg (1.6–2.6mg/kg) and 1.6mg/kg (1.1–2.1mg/kg), respectively, by using the intraperitoneal (i.p.) route of administration in mice. Their maximal antinociceptive efficacy resembled that produced by ketorolac (10mg/kg, i.p.), a common clinic analgesic. ConclusionOur results provide evidence that these triterpenes participate in the antinociceptive activity of R. officinalis. In addition, each individual triterpene showed a similar potency to that observed with ketorolac, a non-steroidal anti-inflammatory drug, in this experimental model.

The aqueous root extract of Aristolochia ringens (Vahl.) prevents chemically induced inflammation

Aristolochia ringens Vahl Aristolochiaceae belongs to a family with many medicinal uses, but also reported toxic (1). Based on its use in traditional medicine, the antiinflammatory activity of the aqueous root extract of Aristolochia ringens (AR) (10–100mg/kg p.o.) was evaluated using the carrageenaan and egg albumin induced rat paw oedema (2), formaldehyde induced arthritic inflammation (3) and xylene induced mouse ear oedema methods (2). AR (10–50mg/kg) produced a dose-dependent decrease in rat paw oedema in the carrageenan and egg albumin induced inflammations at the time intervals studied. The maximum inhibitory effects of AR (50mg/kg), 57.1% and 65.6% in both experiments were comparable to the 57.9% and 63.9% of standard drugs, indomethacin and diclofenac (10mg/kg p.o.) respectively. AR (10–50mg/kg) also dose dependently inhibited the arthritic paw oedema induced by formaldehyde over the 10 day period of study. The maximum inhibition by AR (50mg/kg) (50%) was greater than the 40.8% inhibition by diclofenac (10mg/kg i.p.). AR (10–50mg/kg) also produced a significant (p<0.05) dose dependent inhibition of mouse ear oedema, with a peak effect at 50mg/kg of 84.78%, which was greater than the 65.21% inhibition by dexamethasone (1mg/kg). No mortality was observed in 24 hours, with AR (up to 10g/kg p.o.), but an LD50 of 453mg/kg was obtained with the intraperitoneal route of administration in mice. Results suggest that the aqueous root extract of Aristolochia ringens possesses antiinflammatory activity, inhibiting chemically induced inflammation.

Potential Carcinogenicity of Chloral Hydrate–A Review

Chloral hydrate is commonly used to sedate children for diagnostic or therapeutic procedures. The drug has been extensively used for many years, but there are remarkably few data on its long-term health effects. Concern in this regard is raised by recent studies showing chloral hydrate to be genotoxic, causing chromosome changes and other effects in vivo and in vitro. In addition, chloral hydrate is a reactive metabolite of trichloroethylene, a known carcinogen, and is structurally similar to other carcinogenic intermediates. Two carcinogenicity studies performed using the oral route of administration in mice indicate that the drug is potentially carcinogenic--in one case after a single dose lower than the typical dose used for sedation. Practitioners should be aware of chloral hydrate's genotoxicity and potential carcinogenicity. Discretion in its use seems appropriate until further studies clarify its long term health consequences.