madman
Super Moderator
ABSTRACT
Introduction: The use of currently available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED.
Aim: To review the current literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research.
Methods: A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as “erectile dysfunction”, “emerging treatments”, “nanotechnology”, and “herbal medicine”. The retrieved papers were organized into groups according to the sections covered in this review paper.
Main Outcomes Measures: We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine.
Results: Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticles and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments.
Conclusion: A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety.
INTRODUCTION
Male erectile dysfunction (ED) or impotence can be defined as incompetence to reach and retain sufficient penile tumescence for sexual intercourse.1,2 Worldwide, there are more than 152 million men affected by ED and are expected to be 322 million in 2025.1,2 The likelihood of developing ED increases with age, it is most prevalent in men aged 40 years old and above.3-5 ED has been reported to be associated with diabetes6 and radical prostatectomy (RP) used in the treatment of prostate cancer.7-9 Other risk factors for ED include hypertension, cardiovascular diseases, obesity, alcohol intake, cigarette smoking, drug abuse, and poor physical activity.2,10
Currently, oral phosphodiesterase type 5 (PDE5) inhibitors, for example, sildenafil have been endorsed for use by the United States Food and Drug Administration (FDA) as the initial medications for the alleviation and treatment of male ED.2,11,12 This drug class plays an essential role in penile erection. Sexual stimulation leads to the synthesis of nitric oxide (NO) from L-arginine and oxygen by nitric oxide synthase (NOS). NO is released from endothelium and nitrergic nerves then diffuse through the cell membrane into corpora cavernosa smooth muscle and activate the guanylate cyclase. This catalyzes the conformational modification of guanosine-5’-triphosphate (GTP) to form a second messenger called 3’-5’ cyclic guanosine monophosphate (cGMP). In turn, cGMP activates the cGMP-dependent protein kinase (PKG) which causes decreased levels of intracellular calcium, smooth muscle relaxation and vasodilation, and subsequently penile erection. An enzyme, PDE5 degrades the cGMP leading to smooth muscle contraction, vasoconstriction, and penile detumescence. Oral treatment for ED, PDE5 inhibitors bind to the catalytic site of PDE enzymes and block the degradation of 3’,5’-cyclic guanosine monophosphate (cGMP), thus prevents premature penile detumescence and ED.2,11,13,14
PDE5 inhibitors have some limitations. The drugs are not effective, safe, and tolerated by all patients diagnosed with ED.12,13 They are associated with several adverse effects (AEs) attributed to poor aqueous solubility, and low bioavailability.15 The most dominant AEs including headache, dizziness, stuffy nose, feverishness, and indigestion.2,11,13,15 PDE5 inhibitors should not be administered with organic nitrates, due to their synergic effect may result in hypotension and fatal.16,17 Besides, some patients discontinued using these drugs.13 For these reasons, PDE5 inhibitors should be modified.10,12 Also, there is a need for more effective and safe treatment options.2,10,18
Nanotechnology has emerged as a common tool used in medicine, to improve the efficacy and safety of the treatments including minimizing their AEs. It involves the application of nanoparticles (NPs). These have exclusive properties such as possess different shapes, small size (1−100 nm), high surface area to volume ratio, chemical, and physical properties.19-21 Encapsulation of drugs into NPs enhance drugs solubility, reduce toxicity, facilitate delivery at the specific site, control and sustain their release.20,22 At the moment, there are numerous scientific reports on the different nanoparticle delivery systems for the treatment and recuperation of male ED. However, what is insufficient is the comprehensive review that assembles the experimental evidence and logical comments that provides recommendation for the future research in the drug development. Therefore, this article aims to review the current literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and identify gaps for future research.
NANOMEDICINE FOR MEN ERECTILE DYSFUNCTION
PDE5 Inhibitors NPs
Papaverine Hydrochloride NPs
Sialorphin NPs
NO-Loaded NPs
Adipose Tissue-Derived Stem Cells-NPs
Sonic Hedgehog NPs
Herbal Medicine NPs
Curcumin
Myricitrin
Panax Ginseng
CONCLUSION
The application of nanotechnology in ED medicine can revolutionize the treatment of ED. The findings of preclinical studies demonstrated a tremendous potential therapeutic effect against ED. PDE5 inhibitors, papaverine hydrochloride, sialorphin, nitric oxide, adipose tissue-derived stem cells, sonic hedgehog, and medicinal plant extracts or their phytochemicals are promising for ED therapy. However, few clinical studies evaluated the efficacy and safety of these therapies. Therefore, future well-designed large-scale randomized clinical trials of long-term effects are useful in the development of new and adequate medications for ED treatment.
Introduction: The use of currently available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED.
Aim: To review the current literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research.
Methods: A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as “erectile dysfunction”, “emerging treatments”, “nanotechnology”, and “herbal medicine”. The retrieved papers were organized into groups according to the sections covered in this review paper.
Main Outcomes Measures: We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine.
Results: Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticles and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments.
Conclusion: A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety.
INTRODUCTION
Male erectile dysfunction (ED) or impotence can be defined as incompetence to reach and retain sufficient penile tumescence for sexual intercourse.1,2 Worldwide, there are more than 152 million men affected by ED and are expected to be 322 million in 2025.1,2 The likelihood of developing ED increases with age, it is most prevalent in men aged 40 years old and above.3-5 ED has been reported to be associated with diabetes6 and radical prostatectomy (RP) used in the treatment of prostate cancer.7-9 Other risk factors for ED include hypertension, cardiovascular diseases, obesity, alcohol intake, cigarette smoking, drug abuse, and poor physical activity.2,10
Currently, oral phosphodiesterase type 5 (PDE5) inhibitors, for example, sildenafil have been endorsed for use by the United States Food and Drug Administration (FDA) as the initial medications for the alleviation and treatment of male ED.2,11,12 This drug class plays an essential role in penile erection. Sexual stimulation leads to the synthesis of nitric oxide (NO) from L-arginine and oxygen by nitric oxide synthase (NOS). NO is released from endothelium and nitrergic nerves then diffuse through the cell membrane into corpora cavernosa smooth muscle and activate the guanylate cyclase. This catalyzes the conformational modification of guanosine-5’-triphosphate (GTP) to form a second messenger called 3’-5’ cyclic guanosine monophosphate (cGMP). In turn, cGMP activates the cGMP-dependent protein kinase (PKG) which causes decreased levels of intracellular calcium, smooth muscle relaxation and vasodilation, and subsequently penile erection. An enzyme, PDE5 degrades the cGMP leading to smooth muscle contraction, vasoconstriction, and penile detumescence. Oral treatment for ED, PDE5 inhibitors bind to the catalytic site of PDE enzymes and block the degradation of 3’,5’-cyclic guanosine monophosphate (cGMP), thus prevents premature penile detumescence and ED.2,11,13,14
PDE5 inhibitors have some limitations. The drugs are not effective, safe, and tolerated by all patients diagnosed with ED.12,13 They are associated with several adverse effects (AEs) attributed to poor aqueous solubility, and low bioavailability.15 The most dominant AEs including headache, dizziness, stuffy nose, feverishness, and indigestion.2,11,13,15 PDE5 inhibitors should not be administered with organic nitrates, due to their synergic effect may result in hypotension and fatal.16,17 Besides, some patients discontinued using these drugs.13 For these reasons, PDE5 inhibitors should be modified.10,12 Also, there is a need for more effective and safe treatment options.2,10,18
Nanotechnology has emerged as a common tool used in medicine, to improve the efficacy and safety of the treatments including minimizing their AEs. It involves the application of nanoparticles (NPs). These have exclusive properties such as possess different shapes, small size (1−100 nm), high surface area to volume ratio, chemical, and physical properties.19-21 Encapsulation of drugs into NPs enhance drugs solubility, reduce toxicity, facilitate delivery at the specific site, control and sustain their release.20,22 At the moment, there are numerous scientific reports on the different nanoparticle delivery systems for the treatment and recuperation of male ED. However, what is insufficient is the comprehensive review that assembles the experimental evidence and logical comments that provides recommendation for the future research in the drug development. Therefore, this article aims to review the current literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and identify gaps for future research.
NANOMEDICINE FOR MEN ERECTILE DYSFUNCTION
PDE5 Inhibitors NPs
Papaverine Hydrochloride NPs
Sialorphin NPs
NO-Loaded NPs
Adipose Tissue-Derived Stem Cells-NPs
Sonic Hedgehog NPs
Herbal Medicine NPs
Curcumin
Myricitrin
Panax Ginseng
CONCLUSION
The application of nanotechnology in ED medicine can revolutionize the treatment of ED. The findings of preclinical studies demonstrated a tremendous potential therapeutic effect against ED. PDE5 inhibitors, papaverine hydrochloride, sialorphin, nitric oxide, adipose tissue-derived stem cells, sonic hedgehog, and medicinal plant extracts or their phytochemicals are promising for ED therapy. However, few clinical studies evaluated the efficacy and safety of these therapies. Therefore, future well-designed large-scale randomized clinical trials of long-term effects are useful in the development of new and adequate medications for ED treatment.
