Transdermal water-in-oil nanocarriers of nitric oxide for triggering penile erection

Abstract

Men’s sexual health can have significant effects on a man’s self-esteem, sexual relationship and male reproductive functions. Although commercially available drugs (e.g., VIAGRA and CIALIS) show effective treatment of erectile dysfunction (ED), patients with severe ED fail to respond to these medicines. Topical nitric-oxide (NO) delivery to penis can be a painless, alternative solution with severe ED because NO triggers erection and diffuses to the trabecular arteries and smooth muscles in the penis. We here develop water-in-oil (W/O) nanoemulsions (NEs) that contain NO and can directly spread on the penis. We optimize NE formation conditions including hydrophilic-lipophilic balance (HLB) and ratio of oil, water and surfactants. Then, by spreading NEs on penis skin of intact middle aged dogs, we verify medication effects and safety of the NEs in vivo. The water-in-oil NEs can be a promising non-invasive medication for ED patients with low response to a phosphodiesterase type 5 (PDE5) inhibitor, thus increasing quality of life in the aging society.

The relationship between the severity of erectile dysfunction and aortic stiffness

“…Blocking nitric oxide synthesis increases local arterial stiffness. NO is one of the most crucial mediators in erection physiology (Kinlay et al, 2001;Nam, Yoo, Kim, Kim, & Heo, 2018;Wilkinson et al, 2002). The fact that NO is involved in aetiology of both ED and arteriosclerosis is suggestive of an association between these two conditions.…”

Advances in Nanoparticle Delivery System for Erectile Dysfunction: An Updated Review

“…The study concluded that NO-NEs could be used as a topical drug delivery system for the treatment of ED patients and those who have poor drug reactions to phosphodiesterase 5 inhibitors. 50 This study is promising, but there is limited evidence on its use for the treatment of ED in humans. However, more clinical research is needed to evaluate the therapeutic efficacy and safety before is recommended for humans.…”

“…Shortly, we should conduct clinical research that evaluates the efficacy and safety of this novel NO nanoparticle gel for the mitigation of male ED. In another study by Nam et al 50 prepared NO loaded waterin-oil (w/o) nanoemulsions (NEs) and examined the safety and efficacy of topical application of NO-NEs on the penile skin of anesthetized and unanaesthetised 4 male dogs aged 7 and 8 years old (» middle-aged male) (Table 1). The diameter of the penis, redness of skin, blood NOx concentration in the penis was used to assess the penile erection.…”

Bio-Functional Textiles: Combining Pharmaceutical Nanocarriers with Fibrous Materials for Innovative Dermatological Therapies

“…Chemical enhancement instead consists of adjusting the drug formulation by adding appropriate chemical substances that cause the swelling of skin barrier [104]. A further skin penetration enhancement strategy consists of the incorporation of the active substance into nanocarriers; such devices can be designed in order to possess physical and chemical properties that allow them to drive the drug across the skin barrier to reach the systemic circulation without affecting the outer skin integrity [105,106]. Moreover, it is possible to combine some pharmaceutical nanocarriers with textile material in order to produce wearable drug delivery devices.…”

“…In the work of Pereira [123] adapalene (logP = 8.5) loaded PCL nanocapsules were produced and topically applied: the high hydrophobicity of both carrier and drug facilitated diffusion in the SC but no further penetration was observed, making the system suitable for topical administration. Marto et al [70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124] incorporated an anti-inflammatory drug in starch-shelled nanoparticles by emulsion solvent evaporation method. The potential effectiveness of such topical formulation was evaluated both in vitro and in vivo on ra...…”