Megalin-targeting liposomes for placental drug delivery

Alfaifi, Ali; Heyder, Rodrigo S.; Bielski, Elizabeth; Almuqbil, Rashed M.; Kavdia, Mahendra; Gerk, Phillip M.; Rocha, Sandro R. P. da

doi:10.1016/j.jconrel.2020.05.033

Cited by 35 publications

(20 citation statements)

References 64 publications

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“…In animal models, targeted liposomes have been used for delivery of indomethacin to the uterus, for the treatment of pre-term labor [38,39]. Similarly, targeted liposomes have been used to deliver insulin-like growth factor-I and -II [7], SE175 [29] and gentamicin [40] to the placenta, to increase trophoblast proliferation, improve uteroplacental blood flow and enhance placental liposome uptake, respectively. There are few reported studies of liposomal uptake and drug delivery in human placental explants, other than our own.…”

Section: Discussionmentioning

confidence: 99%

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

et al. 2021

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Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.

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Section: Discussionmentioning

confidence: 99%

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

et al. 2021

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“…To go further, it could be interesting to design new nanosystems such as targeting nanoparticles, such as liposomes, for placental MRI. As liposomes already showed their value as contrast agent delivery systems but also as placental targeting nanocarriers, it seems natural to consider them to ensure a specific delivery of the contrast agent to the placenta to ensure the safety of usage for both the mother and the fetus [110][111][112]. Ultimately, any use of nanomaterials in pregnancy should still require a cautious and extensive risk-benefit evaluation.…”

Section: Discussionmentioning

confidence: 99%

How Could Nanomedicine Improve the Safety of Contrast Agents for MRI during Pregnancy?

Difonzo

Fliedel

Mignet

et al. 2022

Sci

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Pregnancy is a delicate state, during which timely investigation of possible physiological anomalies is essential to reduce the risk of maternal and fetal complications. Medical imaging encompasses different technologies to image the human body for the diagnosis, course of treatment management, and follow-up of diseases. Ultrasound (US) is currently the imaging system of choice for pregnant patients. However, sonographic evaluations can be non-effective or give ambiguous results. Therefore, magnetic resonance imaging (MRI), due to its excellent tissue penetration, the possibility of acquisition of three-dimensional anatomical information, and its high spatial resolution, is considered a valid diagnostical alternative. Nevertheless, currently employed contrast agents to improve the MRI image quality are harmful to the fetus. Because of their ability to cross the placenta, their use on pregnant patients is avoided. This review will firstly recapitulate the most common non-obstetrical, obstetrical, and fetal indications for magnetic resonance imaging on pregnant women. Fetal safety risks, due to the use of strong magnetic fields and exogenous contrast agents, will be presented. Then, possible advantages of nanostructured contrast agents compared to current molecular ones are explored. Nanosystems’ characteristics affecting contrast efficiency, and their potential for improving contrast-enhanced MRI’s safety in pregnant women, are discussed. Lastly, promising examples of nanoparticles as safer alternatives to current MRI contrast agents in pregnancy are discussed.

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“…Liposomes were synthesized using a thin‐film hydration method 39–41 . Specifically, in a round‐bottom flask, 2 mg of Fer‐1 (or 3 mg Dex), 8 mg of cholesterol, 10 mg of DSPE‐mPEG, and 30 mg of soybean lecithin (molar ratio, 2:5:1:10) were added to 10 ml of methylene chloride and dissolved completely.…”

Section: Methodsmentioning

confidence: 99%

“…Liposomes were synthesized using a thin-film hydration method. [39][40][41] Specifically, in a round-bottom flask, 2 mg of Fer-1 (or 3 mg Dex), 8 mg of cholesterol, 10 mg of DSPE-mPEG, and 30 mg of soybean lecithin (molar ratio, 2:5:1:10) were added to 10 ml of methylene chloride and dissolved completely. The mixture was evaporated using a rotary evaporator under reduced pressure until a homogeneous phospholipid film formed.…”

Section: Liposomes Preparation and Characterizationmentioning

confidence: 99%

Ferrostatin‐1‐loaded liposome for treatment of corneal alkali burn via targeting ferroptosis

Wang

Jiang

Zhong

et al. 2021

Bioengineering & Transla Med

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Alkali burn is a potentially blinding corneal injury. During the progression of alkali burn‐induced injury, overwhelmed oxidative stress in the cornea triggers cell damage, including oxidative changes in cellular macromolecules and lipid peroxidation in membranes, leading to impaired corneal transparency, decreased vision, or even blindness. In this study, we identified that ferroptosis, a type of lipid peroxidation‐dependent cell death, mediated alkali burn‐induced corneal injury. Ferroptosis‐targeting therapy protected the cornea from cell damage and neovascularization. However, the specific ferroptosis inhibitor ferrostatin‐1 (Fer‐1) is hydrophobic and cannot be directly applied in the clinic. Therefore, we developed Fer‐1‐loaded liposomes (Fer‐1‐NPs) to improve the bioavailability of Fer‐1. Our study demonstrated that Fer‐1‐NPs exerted remarkable curative effects regarding corneal opacity and neovascularization in vivo. The efficacy was comparable to that of dexamethasone, but without appreciable side effects. The significant suppression of ferroptosis (induced by lipid peroxidation and mitochondria disruption), inflammation, and neovascularization might be the mechanisms underlying the therapeutic effect of Fer‐1‐NPs. Moreover, the Fer‐1‐NPs treatment showed no signs of cytotoxicity, hematologic toxicity, or visceral organ damage, which further confirmed the biocompatibility. Overall, Fer‐1‐NPs provide a new prospect for safe and effective therapy for corneal alkali burn.

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Megalin-targeting liposomes for placental drug delivery

Cited by 35 publications

References 64 publications

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

How Could Nanomedicine Improve the Safety of Contrast Agents for MRI during Pregnancy?

Ferrostatin‐1‐loaded liposome for treatment of corneal alkali burn via targeting ferroptosis

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