Intranasal delivery of systemic-acting drugs: Small-molecules and biomacromolecules

Fortuna, Ana; Alves, Gilberto; Serralheiro, Ana; Sousa, Jorge; Falcão, Amílcar

doi:10.1016/j.ejpb.2014.03.004

Cited by 159 publications

(103 citation statements)

References 226 publications

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“…However, the potencies of IN fentanyl, buprenorphine, and NLX in the present study were consistent with those in the published literature using parenteral routes of administration that result in systemic drug absorption (e.g., IM, subcutaneous, IV). The volume and concentration of drug administered have also been identified as important variables for intranasal delivery (Dhuria et al, 2010;Grassin-Delyle et al, 2012;Landis et al, 2012;Fortuna et al, 2014). For humans, solution volumes between 50 and 200 ml are considered best practice, but such guidelines for the rhesus monkey have not been as thoroughly established.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, IN administration is used for a variety of therapeutics, including vaccines, chemotherapies, and analgesics. Studies performed in rodents and primates have demonstrated that IN drug administration circumvents hepatic first-pass metabolism, avoids gastrointestinal decomposition and provides a rapid onset of action (e.g., Dhuria et al, 2010;Fortuna et al, 2014). In humans and nonhuman primates, drug delivered into the nasal cavity is primarily deposited in the respiratory zone located between the inferior and middle turbinate, and is absorbed into the systemic circulation (Pires et al, 2009;Grassin-Delyle et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the opioid antagonist naloxone (NLX) is used routinely to treat opioid toxicity, frequently by IN administration. Naloxone was once only available to paramedics and other clinical personnel, but a concerted effort has widened access as a response to the US opioid epidemic (Wermeling, 2013;Fortuna et al, 2014;Rando et al, 2015). Naloxone "kits" are now being distributed to a broader range of first responders, including police officers, as well as opioid users themselves.…”

Section: Introductionmentioning

confidence: 99%

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Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Saccone

Lindsey

Koeppe

et al. 2016

J Pharmacol Exp Ther

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The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [11 C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Saccone

Lindsey

Koeppe

et al. 2016

J Pharmacol Exp Ther

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“…2,8 To increase delivery efficiency, poly(lactic-co-glycolic acid) (PLGA) nano-/microparticles (NPs/MPs) have been extensively explored for intranasal vaccination with numerous antigens, such as epitope peptides, antigenic proteins, lipoproteins and plasmid DNA. 4,7,9 Similar to antigen delivery system, PLGA micro-/nanoparticulate formulations have many advantages over soluble formulations. PLGA NPs/MPs can limit antigen degradation by protease, targeting antigens to antigen presenting cells (APCs) and control release rates of antigen.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-<em>co</em>-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

Dai¹,

He²,

Zhang³

et al. 2017

IJN

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The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic- co -glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism. After uptake of MPs by macrophages, MC-PLGA MPs existed both in the endo-some and in the cytoplasm. FLN and pI:C in solution or MP formulation could synergize to activate macrophages and induce higher pro-inflammatory cytokines interleukin (IL)-6, IL-12, interferon-γ and anti-inflammatory cytokines IL-10 compared to single TLR ligand ( P <0.05). In vivo immunogenicity studies indicated that co-delivery of FLN and pI:C within MC-PLGA MPs synergistically induced higher serum anti-HBsAg IgG levels and Th1 cytokine levels compared with MC-PLGA MPs encapsulated single TLR ligand plus MPs encapsulated HBsAg ( P <0.05). These results suggest that synergic TLR3 and TLR5 stimulation might be a promising novel tool for nasally delivered HBsAg.

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“…The range of drugs investigated for possible nasal application varies from lipophilic drugs to polar and hydrophilic molecules, including peptides and proteins. [1][2][3] It offers an attractive alternative application for drugs that have limited oral bioavailability, are degradable by gastrointestinal fluid, or undergo high hepatic first-pass or gut-wall metabolism. In addition, nasal drug administration results in quick onset of action than oral and transdermal applications.…”

mentioning

confidence: 99%

Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface

Tanaka

Furubayashi

Enomura

et al. 2017

Biological & Pharmaceutical Bulletin

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The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.Key words nasal drug absorption; powder formulation; lactose; osmotic pressure; nasal residence; mucociliary clearance Nasal drug application has gained a great deal of attention over the last few decades because of its great potential utility for systemic drug delivery. The range of drugs investigated for possible nasal application varies from lipophilic drugs to polar and hydrophilic molecules, including peptides and proteins.1-3) It offers an attractive alternative application for drugs that have limited oral bioavailability, are degradable by gastrointestinal fluid, or undergo high hepatic first-pass or gut-wall metabolism. In addition, nasal drug administration results in quick onset of action than oral and transdermal applications. 4,5) Because nasal administration is easier and less invasive than oral delivery, not only for the elderly but also for long-term-care patients with swallowing difficulties, it has considerable clinical potential for improving the QOL of both patients and care givers.

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Intranasal delivery of systemic-acting drugs: Small-molecules and biomacromolecules

Cited by 159 publications

References 226 publications

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-<em>co</em>-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface

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