Chitosans as nasal absorption enhancers of peptides: comparison between free amine chitosans and soluble salts

Tengamnuay, Parkpoom; Sahamethapat, Amorn; Sailasuta, Achariya; Mitra, Ashim K.

doi:10.1016/s0378-5173(99)00451-2

Cited by 104 publications

(57 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rats were then sacrificed and their nasal septum with the epithelial cell membrane was isolated (15,22), fixed in 10% formaldehyde for 24 h, decalcified, washed with water, and then dehydrated by ethyl alcohol. Specimens were cleared in xylene then embedded in paraffin at 56°C in a hot air oven for 24 h. Tissue blocks of paraffin beeswax were then prepared for sectioning at 5 μm by slide microtone.…”

Section: Tolerability and Toxicity Studies (Histopathological Studies)mentioning

confidence: 99%

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

et al. 2016

View full text Add to dashboard Cite

Abstract. Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to firstpass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 2 3 factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q 24 ) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.

show abstract

Section: Tolerability and Toxicity Studies (Histopathological Studies)mentioning

confidence: 99%

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

et al. 2016

View full text Add to dashboard Cite

show abstract

“…With a molecular weight that is 10-fold less than that of HC, D-KTP is a considerably smaller peptide that would be expected to enter the nasal vasculature and be affected by a vasoconstrictor to a greater extent than HC. To date, the only investigations of nasal formulations of D-KTP have been conducted in in situ nasal absorption studies with absorption enhancers (Tengamnuay and Mitra, 1990;Tengamnuay et al, 2000). In addition, there is one report of intranasal administration of L-Tyr-L-Arg demonstrating neuroprotective effects in rats (Nazarenko et al, 1999) …”

mentioning

confidence: 99%

Novel Vasoconstrictor Formulation to Enhance Intranasal Targeting of Neuropeptide Therapeutics to the Central Nervous System

Dhuria

Hanson²,

Frey³

2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The intranasal route of drug administration is noninvasive, convenient, and rapidly targets therapeutics to the central nervous system (CNS) using olfactory and trigeminal neural pathways connecting the nasal passages to the brain. The purpose of this research was to enhance intranasal drug targeting to the CNS by incorporating a vasoconstrictor [phenylephrine (PHE)] into nasal formulations containing therapeutic neuropeptides [hypocretin-1 (HC) or the dipeptide L-Tyr-D-Arg (D-KTP)]. Concentrations in CNS tissues, peripheral tissues, and blood were determined at 30 min following intravenous or intranasal administration of 125 I-labeled neuropeptides with and without PHE. Compared with intranasal controls, inclusion of 1% PHE in nasal formulations significantly reduced absorption into the blood for HC (65% reduction) and D-KTP (56% reduction), whereas it significantly increased deposition into the olfactory epithelium by ϳ3-fold for both. PHE (1%) significantly increased delivery to the olfactory bulbs for HC (2.1-fold) and D-KTP (3.0-fold), whereas it significantly reduced concentrations in the trigeminal nerve for HC (65% reduction) and D-KTP (39% reduction) and in most remaining brain regions by ϳ50% for both. The dramatic reduction in blood concentrations with PHE contributed to brain-to-blood concentration ratios that were significantly increased for HC throughout the brain (1.6 -6.8-fold) compared with intranasal controls. For D-KTP, 1% PHE significantly increased ratios only in the olfactory bulbs (5.3-fold). With a 5% PHE formulation, D-KTP ratios were significantly increased to additional brain areas (1.5-16-fold). Vasoconstrictor nasal formulations may have particular relevance for CNS therapeutics with adverse side effects where it would be advantageous to limit systemic exposure.It has been reported that greater than 98% of small-molecule and nearly 100% of large-molecule central nervous system (CNS) drugs developed by the pharmaceutical industry do not cross the blood-brain barrier (Pardridge, 2005). Intracerebroventricular or intraparenchymal drug administration can directly deliver therapeutics to the brain; however, these methods are invasive, inconvenient, and impractical for the numbers of individuals requiring therapeutic interventions for treating CNS disorders. Intranasal drug administration is a noninvasive and convenient means to rapidly target therapeutics of varying physical and chemical properties to the CNS. Although the exact mechanisms underlying intranasal delivery to the CNS are not well understood, the olfactory and trigeminal neural pathways connecting the nasal passages to the CNS are clearly involved (Thorne et al

show abstract

“…Study by Tengamnuay et al suggested that chitosans should differ in their MW by at least twofold in order to have a clearly differentiating effect on the nasal absorption enhancement of a kyotorphin analogue 61 . On the contrary, there is no significant difference between the constants of intranasal absorption for metoclopramide HCl administered with chitosan high weight (600 kDa) and low weight (150 kDa) even though they differ in MW by fourfold 62 .…”

Section: Mucoadhesive Polymers Used In Nasal Drug Deliverymentioning

confidence: 99%

Untitled

2017

IJPSR

View full text Add to dashboard Cite

Nasal drug delivery has been recognized as a promising route for delivery of therapeutic compounds including biopharmaceuticals. It has been demonstrated that absorption of drugs can enhanced by using absorption enhancers or increasing the drug residence time in the nasal cavity. Mucoadhesive polymers can serve both functions. The residence time in the nasal cavity is considerably increased for microspheres compared to solutions. However, this is not the only factor to increase the absorption of large hydrophilic drugs. Microspheres also exert a direct effect on the mucosa, resulting in the opening of tight junctions between the epithelial cells. This review focuses on the background of nasal mucoadhesive drug delivery with special references to the biological and pharmaceutical considerations for nasal mucoadhesive drug administration.

show abstract

Chitosans as nasal absorption enhancers of peptides: comparison between free amine chitosans and soluble salts

Cited by 104 publications

References 32 publications

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery

Novel Vasoconstrictor Formulation to Enhance Intranasal Targeting of Neuropeptide Therapeutics to the Central Nervous System

Untitled

Contact Info

Product

Resources

About