Rapid Absorption of Dry-Powder Intranasal Oxytocin

Milewski, Mikolaj; Goodey, Adrian; Lee, Dinah; Rimmer, Eric; Saklatvala, Robert; Koyama, Shuzo; Iwashima, Mic; Haruta, Shunji

doi:10.1007/s11095-016-1929-x

Cited by 17 publications

(5 citation statements)

References 12 publications

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“…Thus, its activation should partially account for the increased plasma ACTH and the subsequently increased plasma corticosterone levels following IAO. In addition, because lactating rats exhibited a high degree of CRH and VP colocalization in parvocellular PVN neurons, hypothalamic projections, and median eminence terminals compared to virgins, it is possible for a simultaneous increase in VP and CRH in the PVN (Milewski et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms

Liu

et al. 2019

Front. Neurosci.

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Oxytocin (OT), a hypothalamic neuropeptide, applied through nasal approach (IAO), could improve maternal health during lactation that is disrupted by mother–baby separation; however, the regulation of IAO effects on maternal behaviors and lactation as well as the underlying mechanisms remain unclear. Using lactating rats, we observed effects of intermittent pup deprivation (PD) with and without IAO on maternal behaviors and lactation as well as the activity of OT neurons in the supraoptic nucleus (SON) and the activity of hypothalamic pituitary-adrenal axis, key factors determining the milk-letdown reflex during lactation and maternal behaviors. The results showed that PD reduced maternal behaviors and lactation efficiency of rat dams as indicated by significantly longer latency to retrieve their pups and low litter’s body weight gains during the observation, respectively. In addition, PD caused early involution of the mammary glands. IAO partially improved these changes in rat dams, which was not as significant as IAO effects on control dams. In the SON, PD decreased c-Fos and increased glial fibrillary acidic protein (GFAP) filaments significantly; IAO made PD-evoked c-Fos reduction insignificant while reduced GFAP filament significantly in PD dams. IAO tended to increase the levels of phosphorylated extracellular signal-regulated kinases (pERK) 1/2 in PD dams. Moreover, PD+IAO significantly increased plasma levels of dam adrenocorticotropic hormone and corticosterone but not OT levels. Lastly, PD+IAO tended to increase the level of corticotropin-releasing hormone in the SON. These results indicate that PD disrupts maternal behaviors and lactation by suppressing the activity of hypothalamic OT-secreting system through expansion of astrocytic processes, which are partially reversed by IAO through removing astrocytic inhibition of OT neuronal activity. However, the improving effect of IAO on the maternal health could be compromised by simultaneous activation of hypothalamic pituitary-adrenocortical axis.

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Section: Discussionmentioning

confidence: 99%

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms

Liu

et al. 2019

Front. Neurosci.

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“…Both these demonstrate good safety profile, fast absorption and rapid onset of action. Intranasal powder formulations of different drugs such as oxytocin and dihydroergotamine are also under development [ 79 , 80 ]. It has been suggested that powder formulation is more likely to trigger local irritation than its equivalent liquid formulation, a particular consideration in chronic use.…”

Section: Intranasal Deliverymentioning

confidence: 99%

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

Lam

Cheung

Chow

et al. 2020

Advanced Drug Delivery Reviews

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The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients.

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“…Moreover, it is now under clinical evaluation for delivery of fluticasone propionate for the treatment of chronic rhinosinusitis (Djupesland, 2013;Hansen et al, 2010). Pharmacokinetic studies in monkeys have revealed good in vivo absorption rate of oxytocin from the dry powder of the active with co ® carrier, rapid onset of the effect and reasonable nasal bioavailability (12% of intramuscular bioavailability) (Milewski et al, 2016).…”

Section: Nasal Powder Insufflatorsmentioning

confidence: 99%

Opportunity and challenges of nasal powders: Drug formulation and delivery

Fasiolo

Manniello

Tratta

et al. 2018

European Journal of Pharmaceutical Sciences

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In the field of nasal drug delivery, among the preparations defined by the European Pharmacopoeia, nasal powders facilitate the formulation of poorly water-soluble active compounds. They often display a simple composition in excipients (if any), allow for the administration of larger drug doses and enhance drug diffusion and absorption across the mucosa, improving bioavailability compared to nasal liquids. Despite the positive features, however, nasal products in this form still struggle to enter the market: the few available on the market are Onzetra Xsail® (sumatriptan) for migraine relief and, for the treatment of rhinitis, Rhinocort® Turbuhaler® (budesonide), Teijin Rhinocort® (beclomethasone dipropionate) and Erizas® (dexamethasone cipecilate). Hence, this review tries to understand why nasal powder formulations are still less common than liquid ones by analyzing whether this depends on the lack of (i) real evidence of superior therapeutic benefit of powders, (ii) therapeutic and/or commercial interest, (iii) efficient manufacturing methods or (iv) availability of suitable and affordable delivery devices. To this purpose, the reader's attention will be guided through nasal powder formulation strategies and manufacturing techniques, eventually giving up-to-date evidences of therapeutic efficacy in vivo. Advancements in the technology of insufflation devices will also be provided as nasal drug products are typical drug-device combinations.

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Rapid Absorption of Dry-Powder Intranasal Oxytocin

Abstract: The PK and stability data suggests that IN administration of oxytocin formulated in the μco™ carrier may represent a viable option for rapid systemic absorption in humans and a product compatible with resource-scarce regions.

Cited by 17 publications

References 12 publications

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

Opportunity and challenges of nasal powders: Drug formulation and delivery

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