Liposomes: a nanoscale drug carrying system to prevent indomethacin passage to the fetus in a pregnant mouse model.
Objective: Indomethacin (IND) is a prostaglandin production inhibitor that reduces uterine contractions, but crosses the placenta leading to adverse fetal effects. Liposomes (LIP) are nanoscale systems clinically used to preferentially deliver a drug to the tissue of interest and simultaneously prev...
| Publicado en: | American Journal of Obstetrics & Gynecology Vol. 212; no. 4; pp. 508.e1 - 5081 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Elsevier B.V.
Apr2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=109780054&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109780054 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00029378 AOG jtl: American Journal of Obstetrics & Gynecology issn: 00029378 maglogo: N pubinfo: dt: Apr2015 vid: 212 iid: 4 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 109780054 109780054 NLM25683966 2012962736 10.1016/j.ajog.2015.02.006 NLM25683966 109780054 ppf: 508.e1 ppct: 1 formats: tig: atl: Liposomes: a nanoscale drug carrying system to prevent indomethacin passage to the fetus in a pregnant mouse model. aug: au: Refuerzo, Jerrie S Alexander, Jenolyn F Leonard, Fransisca Leon, Mateo Longo, Monica Godin, Biana affil: Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, TX. Electronic address: Jerrie.S.Refuerzo@uth.tmc.edu. sug: subj: Indomethacin Administration and Dosage Tocolytic Agents Administration and Dosage Administration, Oral Animal Studies Biological Markers Metabolism Dinoprostone Metabolism Female Indomethacin Pharmacodynamics Indomethacin Pharmacokinetics Injections, Intravenous Maternal-Fetal Exchange Membranes, Artificial Mice Pregnancy Tocolytic Agents Pharmacodynamics Tocolytic Agents Pharmacokinetics Uterus Drug Effects Uterus Metabolism Female ab: Objective: Indomethacin (IND) is a prostaglandin production inhibitor that reduces uterine contractions, but crosses the placenta leading to adverse fetal effects. Liposomes (LIP) are nanoscale systems clinically used to preferentially deliver a drug to the tissue of interest and simultaneously prevent distribution to unwanted locations. Our objective was to determine whether LIP could prevent the transfer of IND across the placenta to the fetus while preserving its pharmacological activity.Study Design: Multilamellar LIP were designed with a 150- to 200-nm size, fluorescently labeled, and loaded with IND. Timed pregnant CD1 mice (n = 6/group) on gestational day 18 were administered LIP, LIP-IND (1 mg IND/kg), or saline (SAL) via tail vein injection, or IND (1 mg/kg) via oral gavage. After 4 hours, the uterus, placenta, and fetuses were retrieved. LIP levels were visualized using fluorescent microscopy and quantitatively assessed by National Institutes of Health image processing software. LIP brightness values (mean ± SEM) in arbitrary units (AU) were normalized to the autofluorescence of the same tissue (as measured in SAL group). IND and prostaglandin E2 levels were assessed using liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay, respectively.Results: The qualitative analysis of LIP distribution revealed that the system was primarily confined within the uterus, minimally detected within the placenta, and absent in the fetus. LIP fluorescence was greater in the uterus compared to placenta and fetus (uterus 15.3 ± 5.4 AU vs placenta 3.0 ± 3.5 AU vs fetus 4.4 ± 2.5 AU; P = .009). LIP-IND resulted in a 7.6-fold reduction in the IND levels in the fetus compared to IND alone (LIP-IND 10.7 ± 17.1 ng/g vs IND 81.3 ± 24.7 ng/g; P = .041). Prostaglandin E2 levels were significantly reduced in the uterus of animals given LIP-IND and IND compared to LIP and SAL.Conclusion: LIP localized within the uterus and did not cross the placenta to the fetus. IND within the fetus was reduced 7.6-fold while encapsulated within the LIP and the pharmacologic effects of IND were maintained. Thus, LIP provide a novel therapeutic approach to correct the primary clinical limitation of IND by reducing placental passage to the fetus. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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