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Research Papers

A Novel Intranasal Spray Device for the Administration of Nanoparticles to Rodents

[+] Author and Article Information
Justin E. Piazza

Department of Psychiatry and
Behavioural Neurosciences,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: piazzaje@mcmaster.ca

Chao Zhu

Department of Mechanical Engineering,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: zhuchao.zhuc4@gmail.com

P. Ravi Selvaganapathy

Department of Mechanical Engineering,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: selvaga@mcmaster.ca

Todd R. Hoare

Department of Chemical Engineering,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: hoaretr@mcmaster.ca

Saransh B. Jain

Department of Mechanical Engineering,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: jains33@mcmaster.ca

Farhat Hossain

Department of Psychiatry and
Behavioural Neurosciences,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: hossaift@mcmaster.ca

Ram K. Mishra

Department of Psychiatry and
Behavioural Neurosciences,
Faculty of Health Sciences,
McMaster University,
1200 Main Street West,
Hamilton, ON L8N 3Z5, Canada
e-mail: mishrar@mcmaster.ca

1Corresponding author.

Manuscript received August 13, 2014; final manuscript received February 11, 2015; published online August 6, 2015. Assoc. Editor: Rupak K. Banerjee.

J. Med. Devices 9(4), 041001 (Aug 06, 2015) (9 pages) Paper No: MED-14-1225; doi: 10.1115/1.4029907 History: Received August 13, 2014

Experimental intranasal (IN) delivery of nanoparticle (NP) drug carriers is typically performed using a pipette with or without anesthesia, a technique that may be a poor simulation of practical IN administration of drug-loaded NPs in humans. Existing IN spray devices suffer from drawbacks in terms of variability in dose-control and spray duration as well as the application of nonuniform pressure fields when a NP-formulated drug is aerosolized. Furthermore, existing spray devices require large volumes that may not be available or may be prohibitively expensive to prepare. In response, we have developed a novel pneumatically driven IN spray device for the administration of NPs, which is capable of administering extremely small quantities (50–100 μl) of NP suspension in a fine spray that disperses the NPs uniformly onto the tissue. This device was validated using haloperidol-loaded Solanum tuberosum lectin (STL)-functionalized, poly(ethylene glycol)–block-poly(d,l-lactic-co-glycolic acid) (PEG–PLGA) NPs targeted for delivery to the brain for schizophrenia treatment. A pneumatic pressure of 100 kPa was found to be optimal to produce a spray that effectively aerosolizes NP suspensions and delivers them evenly to the olfactory epithelium. IN administration of STL-functionalized NPs using the IN spray device increased brain tissue haloperidol concentrations by a factor of 1.2–1.5× compared to STL-functionalized NPs administered IN with a pipette. Such improved delivery enables the use of lower drug doses and thus offers both fewer local side-effects and lower costs without compromising therapeutic efficacy.

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Figures

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Fig. 1

Schematic outlining the basic physiological structure of the rat nasal cavity and the pathway for aerosol transport

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Fig. 2

Schematic outlining the basic setup of the IN spray device when administering NP suspension into the rat nasal cavity

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Fig. 3

Nasal spray device design: (a) a design of the nozzle (left), (b) a design of the nozzle (front), (c) the device viewed from the top displaying an external view (left), (d) the device viewed from the front displaying an external view, (e) the device viewed from the top displaying an internal view (left), and (f) the device viewed from the side displaying an external view (left)

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Fig. 4

Optical images of nozzle sprays generated using aerosolization pressures of (a) 50 kPa, (b) 100 kPa, and (c) 150 kPa

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Fig. 5

Average spray surface areas following aerosolization of three different samples (water, PEG–PLGA NPs in water, and PEG–PLGA NPs plus methylene blue in water) measured as a function of the applied pressure and the spray distance

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Fig. 6

Cataleptic response rating following drug administration based on the drug treatment received: empty STL-NPs administered IN using anesthesia using a pipette (empty STL-NPs (IN-P + A)), haloperidol STL-NPs administered IN without anesthesia using a pipette (HP-STL-NPs (IN)), haloperidol STL-NPs administered IN with anesthesia using a pipette (HP-STL-NPs (IN-P + A)), and haloperidol STL-NPs administered IN with anesthesia using a nasal spray device (HP-STL-NPs (IN-D + A))

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Fig. 7

Olfactory bulb tissue concentrations of haloperidol following drug administration based on the drug treatment received: empty STL-NPs administered IN using anesthesia using a pipette (empty STL-NPs (IN-P + A)), haloperidol STL-NPs administered IN without anesthesia using a pipette (HP-STL-NPs (IN)), haloperidol STL-NPs administered IN with anesthesia using a pipette (HP-STL-NPs (IN-P + A)), and haloperidol STL-NPs administered IN with anesthesia using a nasal spray device (HP-STL-NPs (IN-D + A))

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Fig. 8

Striatum tissue concentrations of haloperidol following drug administration based on the drug treatment received: empty STL-NPs administered IN using anesthesia using a pipette (empty STL-NPs (IN-P + A)), haloperidol STL-NPs administered IN without anesthesia using a pipette (HP-STL-NPs (IN)), haloperidol STL-NPs administered IN with anesthesia using a pipette (HP-STL-NPs (IN-P + A)), and haloperidol STL-NPs administered IN with anesthesia using a nasal spray device (HP-STL-NPs (IN-D + A))

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