Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction

George Han; Moses Tar; Dwaraka S.R. Kuppam; Adam Friedman; Arnold Melman; Joel Friedman; Kelvin P. Davies

doi:10.1111/j.1743-6109.2009.01507.x

Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction

George Han, Moses Tar, Dwaraka S.R. Kuppam, Adam Friedman, Arnold Melman, Joel Friedman, Kelvin P. Davies

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Introduction: Nanoparticles represent a potential novel mechanism for transdermal delivery of erectogenic agents directly to the penis. Aim: To determine if nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and nitric oxide [NO]) can improve erectile function in a rat model of erectile dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat). Methods: Nanoparticles encapsulating the erectogenic agents were applied as a gel to the glans and penile shaft of anesthetized Sprague-Dawley rats and the intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with or without stimulation of the cavernous nerve. Control nanoparticles were made without encapsulating erectogenic agents and applied in a similar manner in separate experiments. Results: Nanoparticles encapsulating NO caused spontaneous visible erections in the rat, with an average time of onset of 4.5 minutes, duration of 1.42 minutes, and ICP/BP of 0.67 ± 0.14. The sialorphin nanoparticles also caused visible spontaneous erections after an average of 4.5 minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 ± 0.13. The difference in the erectile response between groups of animals treated with NO or sialorphin nanoparticles was significantly different from the control group treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a significant increase in the mean ICP/BP (0.737 ± 0.029) following stimulation of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with a visibly improved erectile response. Conclusions: Nanoparticles encapsulating three different erectogenic agents resulted in increased erectile function when applied to the penis of a rat model of ED. Nanoparticles represent a potential novel route for topical delivery of erectogenic agents which could improve the safety profile for existing orally administered drugs by avoiding effects of absorption and first-pass metabolism, and would be less hazardous than injection.

Original language	English (US)
Pages (from-to)	224-233
Number of pages	10
Journal	Journal of Sexual Medicine
Volume	7
Issue number	1 PART 1
DOIs	https://doi.org/10.1111/j.1743-6109.2009.01507.x
State	Published - Jan 2010

Keywords

Erectile dysfunction
Nanoparticles
Nitric oxide
Sialorphin
Small particle therapy for ED
Transdermal

ASJC Scopus subject areas

Medicine(all)

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10.1111/j.1743-6109.2009.01507.x

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title = "Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction",

abstract = "Introduction: Nanoparticles represent a potential novel mechanism for transdermal delivery of erectogenic agents directly to the penis. Aim: To determine if nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and nitric oxide [NO]) can improve erectile function in a rat model of erectile dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat). Methods: Nanoparticles encapsulating the erectogenic agents were applied as a gel to the glans and penile shaft of anesthetized Sprague-Dawley rats and the intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with or without stimulation of the cavernous nerve. Control nanoparticles were made without encapsulating erectogenic agents and applied in a similar manner in separate experiments. Results: Nanoparticles encapsulating NO caused spontaneous visible erections in the rat, with an average time of onset of 4.5 minutes, duration of 1.42 minutes, and ICP/BP of 0.67 ± 0.14. The sialorphin nanoparticles also caused visible spontaneous erections after an average of 4.5 minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 ± 0.13. The difference in the erectile response between groups of animals treated with NO or sialorphin nanoparticles was significantly different from the control group treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a significant increase in the mean ICP/BP (0.737 ± 0.029) following stimulation of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with a visibly improved erectile response. Conclusions: Nanoparticles encapsulating three different erectogenic agents resulted in increased erectile function when applied to the penis of a rat model of ED. Nanoparticles represent a potential novel route for topical delivery of erectogenic agents which could improve the safety profile for existing orally administered drugs by avoiding effects of absorption and first-pass metabolism, and would be less hazardous than injection.",

keywords = "Erectile dysfunction, Nanoparticles, Nitric oxide, Sialorphin, Small particle therapy for ED, Transdermal",

author = "George Han and Moses Tar and Kuppam, {Dwaraka S.R.} and Adam Friedman and Arnold Melman and Joel Friedman and Davies, {Kelvin P.}",

note = "Funding Information: This work was partly supported by grant R01DK077665 awarded by the NIH/NIDDK to Kelvin P. Davies and partly through a grant to J. M. Friedman from FJC, A Foundation of Philanthropic Funds. We would like to thank Dr. Rani R. Sellers for performing histopathology. ",

year = "2010",

month = jan,

doi = "10.1111/j.1743-6109.2009.01507.x",

language = "English (US)",

volume = "7",

pages = "224--233",

journal = "Journal of Sexual Medicine",

issn = "1743-6095",

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number = "1 PART 1",

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AU - Han, George

AU - Tar, Moses

AU - Kuppam, Dwaraka S.R.

AU - Friedman, Adam

AU - Melman, Arnold

AU - Friedman, Joel

AU - Davies, Kelvin P.

N1 - Funding Information: This work was partly supported by grant R01DK077665 awarded by the NIH/NIDDK to Kelvin P. Davies and partly through a grant to J. M. Friedman from FJC, A Foundation of Philanthropic Funds. We would like to thank Dr. Rani R. Sellers for performing histopathology.

PY - 2010/1

Y1 - 2010/1

N2 - Introduction: Nanoparticles represent a potential novel mechanism for transdermal delivery of erectogenic agents directly to the penis. Aim: To determine if nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and nitric oxide [NO]) can improve erectile function in a rat model of erectile dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat). Methods: Nanoparticles encapsulating the erectogenic agents were applied as a gel to the glans and penile shaft of anesthetized Sprague-Dawley rats and the intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with or without stimulation of the cavernous nerve. Control nanoparticles were made without encapsulating erectogenic agents and applied in a similar manner in separate experiments. Results: Nanoparticles encapsulating NO caused spontaneous visible erections in the rat, with an average time of onset of 4.5 minutes, duration of 1.42 minutes, and ICP/BP of 0.67 ± 0.14. The sialorphin nanoparticles also caused visible spontaneous erections after an average of 4.5 minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 ± 0.13. The difference in the erectile response between groups of animals treated with NO or sialorphin nanoparticles was significantly different from the control group treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a significant increase in the mean ICP/BP (0.737 ± 0.029) following stimulation of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with a visibly improved erectile response. Conclusions: Nanoparticles encapsulating three different erectogenic agents resulted in increased erectile function when applied to the penis of a rat model of ED. Nanoparticles represent a potential novel route for topical delivery of erectogenic agents which could improve the safety profile for existing orally administered drugs by avoiding effects of absorption and first-pass metabolism, and would be less hazardous than injection.

AB - Introduction: Nanoparticles represent a potential novel mechanism for transdermal delivery of erectogenic agents directly to the penis. Aim: To determine if nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and nitric oxide [NO]) can improve erectile function in a rat model of erectile dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat). Methods: Nanoparticles encapsulating the erectogenic agents were applied as a gel to the glans and penile shaft of anesthetized Sprague-Dawley rats and the intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with or without stimulation of the cavernous nerve. Control nanoparticles were made without encapsulating erectogenic agents and applied in a similar manner in separate experiments. Results: Nanoparticles encapsulating NO caused spontaneous visible erections in the rat, with an average time of onset of 4.5 minutes, duration of 1.42 minutes, and ICP/BP of 0.67 ± 0.14. The sialorphin nanoparticles also caused visible spontaneous erections after an average of 4.5 minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 ± 0.13. The difference in the erectile response between groups of animals treated with NO or sialorphin nanoparticles was significantly different from the control group treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a significant increase in the mean ICP/BP (0.737 ± 0.029) following stimulation of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with a visibly improved erectile response. Conclusions: Nanoparticles encapsulating three different erectogenic agents resulted in increased erectile function when applied to the penis of a rat model of ED. Nanoparticles represent a potential novel route for topical delivery of erectogenic agents which could improve the safety profile for existing orally administered drugs by avoiding effects of absorption and first-pass metabolism, and would be less hazardous than injection.

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KW - Nanoparticles

KW - Nitric oxide

KW - Sialorphin

KW - Small particle therapy for ED

KW - Transdermal

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Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction

Abstract

Keywords

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