Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine

Kamiya, Yusuke; Yamaki, Tsutomu; Omori, Shigehiro; Uchida, Masaki; Ohtake, Kazuo; Kimura, Mitsutoshi; Yamazaki, Hiroshi; Natsume, Hideshi

doi:10.3390/ph11010009

Cited by 9 publications

(3 citation statements)

References 26 publications

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“…More drug can be delivered into brain if the Puerarin or Radix Puerariae Extract was combined with volatile oils. Moreover, application of bioadhesive dosage forms (like in situ gel delivery system and bioadhesive delivery system) [ 18 , 19 ] is helpful for the reduction of mucociliary clearance and prolonging of the drug residence time in the nasal cavity [ 20 ], which may also improve the drug distribution in brain.…”

Section: Discussionmentioning

confidence: 99%

Coexisting flavonoids and administration route effect on pharmacokinetics of Puerarin in MCAO rats

Zhong

Yang

et al. 2020

Open Life Sciences

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AbstractA pharmacokinetic comparison was made to evaluate the influence from other components in the Radix Puerariae Extract on pharmacokinetic behavior of Puerarin. Samples of blood and brain were collected by microdialysis and determined by high-performance liquid chromatography–mass spectrometry (MS)/MS. Pharmacokinetic parameters were estimated from the concentration versus time data using non-compartmental methods. In addition, a comparative pharmacokinetic study of Puerarin in stroke rats was studied after administration of the Radix Puerariae Extract via different routes to find an effective way to deliver drug into brain. Obvious pharmacokinetic differences were also observed in comparison between the Puerarin group and the Radix Puerariae Extract group based on middle cerebral artery occlusion (MCAO) rats. The Cmax and area under the curve (AUC) of Puerarin in olfactory bulb of the Extract group significantly reduced when it was intravenously administered. However, the AUCs of Puerarin in plasma are 134.72 and 1707.02 mg/L min, via intranasal and intravenous administration of the Radix Puerariae Extract, respectively. The AUC of the intranasal group in brain is seven times higher than that of intravenous administration. Other ingredients in the Extract may affect the disposition of Puerarin and its transportation through the blood–brain barrier via intravenous administration. But intranasal administration is an effective route to deliver isoflavone-C-glycoside with poor hydrophilicity into brain.

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Section: Discussionmentioning

confidence: 99%

Coexisting flavonoids and administration route effect on pharmacokinetics of Puerarin in MCAO rats

Zhong

Yang

et al. 2020

Open Life Sciences

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“…Recent investigations have shown that PLO enhanced the uptake of FITC-insulin in cultured alveolar type II epithelial cells without cytotoxicity. 21) In addition, the hypoglycemic action of insulin was increased by pulmonary co-administration with PLO in an in vivo rat model. We also reported that PLO improved the in vivo nasal absorption of FD-4, and the improvement was dependent on its concentration.…”

Section: Cytotoxicity Of Plo On the Nasal Mucosamentioning

confidence: 99%

Enhancement Effect of Poly-L-ornithine on the Nasal Absorption of Water-Soluble Macromolecules in Rats

Omori

Kamiya

Yamaki

et al. 2019

Biological & Pharmaceutical Bulletin

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The transnasal route for the delivery of water-soluble macromolecules, such as bioactive peptides and proteins, has attracted interest, although the use of permeation enhancers is required due to the poor permeabilities of these macromolecules across the nasal mucosa. With polycationic compounds, such as poly-L-arginine and chitosan, the nasal absorption of hydrophilic macromolecules is molecular weight-and concentration-dependently enhanced without causing cytotoxicity. In the present study, we evaluated the effect of various molecular weights and concentrations of poly-L-ornithine (PLO), a polycationic compound, on the nasal absorption and the damage to the nasal mucosa in vivo. PLO enhanced the nasal absorption of fluorescein isothiocyanate-dextran (FD-4), used as a model drug, and the bioavailability of FD-4 increased with the concentration of PLO. The enhancement effect was also dependent on the molecular weight. The administration of PLO at a concentration that sufficed for enhancing the nasal absorption had no effect on the activity of lactic dehydrogenase and the protein leakage in the nasal fluid, as indices of nasal mucosa damage. These findings suggest that a transnasal delivery system using PLO is a useful strategy for improving the nasal absorption of water-soluble macromolecules without toxicity to the nasal mucosa.

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“…In terms of achieving the best outcomes for nasal drug delivery, enhancing residence times in the nasal cavity, and improving contact between the API and nasal epithelia or the olfactory nerve are important and common strategies in enhancing the degree of uptake, with modification of the dosage form (e.g., emulsion formulations) or incorporation with mucoadhesive agents (e.g., pectin and chitosan polymers) in the formulation. [ 14 ] We reasoned that supramolecular gels could be ideally suited to this application, given their potential for self‐healing and self‐assembly in situ, combined with their soft rheological properties. Although there has been rising interest in the use of responsive polymer gels for nasal drug delivery, [ 15 ] perhaps surprisingly, in spite of the attention focused on low‐molecular‐weight gelators, [ 3 ] they have not previously been explored in this regard.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self‐Healing Supramolecular Gel

et al. 2021

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This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs-a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood-brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3 H-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.

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Improved Intranasal Retentivity and Transnasal Absorption Enhancement by PEGylated Poly-l-ornithine

Cited by 9 publications

References 26 publications

Coexisting flavonoids and administration route effect on pharmacokinetics of Puerarin in MCAO rats

Coexisting flavonoids and administration route effect on pharmacokinetics of Puerarin in MCAO rats

Enhancement Effect of Poly-L-ornithine on the Nasal Absorption of Water-Soluble Macromolecules in Rats

Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self‐Healing Supramolecular Gel

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