Enhancement of nasal absorption of insulin using chitosan nanoparticles

To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their siz...

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Veröffentlicht in:Pharmaceutical research 1999-10, Vol.16 (10), p.1576-1581
Hauptverfasser: FERNANDEZ-URRUSUNO, R, CALVO, P, REMUNAN-LOPEZ, C, VILA-JATO, J. L, ALONSO, M. J
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container_end_page 1581
container_issue 10
container_start_page 1576
container_title Pharmaceutical research
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creator FERNANDEZ-URRUSUNO, R
CALVO, P
REMUNAN-LOPEZ, C
VILA-JATO, J. L
ALONSO, M. J
description To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size and zeta potential by photon correlation spectroscopy and laser Doppler anemometry, respectively. Insulin loading and release was determined by the microBCA protein assay. The ability of chitosan nanoparticles to enhance the nasal absorption of insulin was investigated in a conscious rabbit model by monitoring the plasma glucose levels. Chitosan nanoparticles had a size in the range of 300-400 nm, a positive surface charge and their insulin loading can be modulated reaching values up to 55% [insulin/nanoparticles (w/w): 55/100]. Insulin association was found to be highly mediated by an ionic interaction mechanism and its release in vitro occurred rapidly in sink conditions. Chitosan nanoparticles enhanced the nasal absorption of insulin to a greater extent than an aqueous solution of chitosan. The amount and molecular weight of chitosan did not have a significant effect on insulin response. Chitosan nanoparticles are efficient vehicles for the transport of insulin through the nasal mucosa.
doi_str_mv 10.1023/A:1018908705446
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L ; ALONSO, M. J</creator><creatorcontrib>FERNANDEZ-URRUSUNO, R ; CALVO, P ; REMUNAN-LOPEZ, C ; VILA-JATO, J. L ; ALONSO, M. J</creatorcontrib><description>To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size and zeta potential by photon correlation spectroscopy and laser Doppler anemometry, respectively. Insulin loading and release was determined by the microBCA protein assay. The ability of chitosan nanoparticles to enhance the nasal absorption of insulin was investigated in a conscious rabbit model by monitoring the plasma glucose levels. Chitosan nanoparticles had a size in the range of 300-400 nm, a positive surface charge and their insulin loading can be modulated reaching values up to 55% [insulin/nanoparticles (w/w): 55/100]. Insulin association was found to be highly mediated by an ionic interaction mechanism and its release in vitro occurred rapidly in sink conditions. Chitosan nanoparticles enhanced the nasal absorption of insulin to a greater extent than an aqueous solution of chitosan. The amount and molecular weight of chitosan did not have a significant effect on insulin response. Chitosan nanoparticles are efficient vehicles for the transport of insulin through the nasal mucosa.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1018908705446</identifier><identifier>PMID: 10554100</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Absorption ; Administration, Intranasal ; Animals ; Biological and medical sciences ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Chemical Phenomena ; Chemistry, Physical ; Chitin - analogs &amp; derivatives ; Chitin - pharmacology ; Chitosan ; Excipients ; General and cellular metabolism. Vitamins ; General pharmacology ; Hypoglycemic Agents - administration &amp; dosage ; Hypoglycemic Agents - pharmacokinetics ; Hypoglycemic Agents - pharmacology ; Insulin - administration &amp; dosage ; Insulin - pharmacokinetics ; Insulin - pharmacology ; Male ; Medical sciences ; Microspheres ; Nasal Mucosa - drug effects ; Nasal Mucosa - metabolism ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. 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L</creatorcontrib><creatorcontrib>ALONSO, M. J</creatorcontrib><title>Enhancement of nasal absorption of insulin using chitosan nanoparticles</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size and zeta potential by photon correlation spectroscopy and laser Doppler anemometry, respectively. Insulin loading and release was determined by the microBCA protein assay. The ability of chitosan nanoparticles to enhance the nasal absorption of insulin was investigated in a conscious rabbit model by monitoring the plasma glucose levels. Chitosan nanoparticles had a size in the range of 300-400 nm, a positive surface charge and their insulin loading can be modulated reaching values up to 55% [insulin/nanoparticles (w/w): 55/100]. Insulin association was found to be highly mediated by an ionic interaction mechanism and its release in vitro occurred rapidly in sink conditions. Chitosan nanoparticles enhanced the nasal absorption of insulin to a greater extent than an aqueous solution of chitosan. The amount and molecular weight of chitosan did not have a significant effect on insulin response. 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Vitamins</subject><subject>General pharmacology</subject><subject>Hypoglycemic Agents - administration &amp; dosage</subject><subject>Hypoglycemic Agents - pharmacokinetics</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin - administration &amp; dosage</subject><subject>Insulin - pharmacokinetics</subject><subject>Insulin - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microspheres</subject><subject>Nasal Mucosa - drug effects</subject><subject>Nasal Mucosa - metabolism</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. 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subjects Absorption
Administration, Intranasal
Animals
Biological and medical sciences
Blood Glucose - drug effects
Blood Glucose - metabolism
Chemical Phenomena
Chemistry, Physical
Chitin - analogs & derivatives
Chitin - pharmacology
Chitosan
Excipients
General and cellular metabolism. Vitamins
General pharmacology
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - pharmacology
Insulin - administration & dosage
Insulin - pharmacokinetics
Insulin - pharmacology
Male
Medical sciences
Microspheres
Nasal Mucosa - drug effects
Nasal Mucosa - metabolism
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rabbits
Stimulation, Chemical
title Enhancement of nasal absorption of insulin using chitosan nanoparticles
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