Table 2. Penetration enhancing techniques for treating onychomycosis.

Category	Technique	Specifications	Procedure	Advantages	Disadvantages	Reference
Mechanical	Nail avulsion	Complete separation of nail plate from other units,	Anesthesia followed by Surgical (physical removal) or chemical (application of urea ointment)	No side effects or long term complications.	Postoperative nail deformity, pain.	[24-26]
	Nail abrasion	Filing or debriment of nail plate so as to increase penetration of topical antifungal drug	Sanding of the nail plate with sandpaper number 150 or 180 attached to dermabrader device	Decreases the critical fungal mass and aids the penetration, better patient acceptability, no complications.	Better efficacy is obtained in combination with topical antifungal agents. Also requires expert help.	[27, 28]
Chemical	Addition of penetration enhancing chemical compounds	Keratolytic agents, enzymes, organic solvents, thiols, mercaptans, hydrophobins	These are added in the topical formulation as penetration enhancers	Enhanced nail permeation, non- invasive, convenient.	Itching, irritation at the site of application.	[28]
Physical	Iontophoresis	Comprises of two electrodes and a power source	Application of small electric current (0.5 mA.cm-2) to enhance penetration	Does not affect nail structure, affordable, patient compliant.	Inappropriate intensity of current, cutaneous side effects.	[28-31]
	Laser therapy	Includes Nd:YAG short pulse and Q switch 1064 nm and the diode 870, 930, and 980 nm	Avulsion/ abrasion of the nail plate followed by laser treatment at 5000W/cm2 power density or applying CO2 laser beam with daily topical antifungal drug	Bypasses systemic toxicity, non- invasive, no teratogenic risks, no photo- ablation.	Tissue damage, photoageing, too many parameters to be controlled for desired results, less specificity, less information, high cost.	[32-34]
	Photodynamic	Employs a light source to excite the photo-sensitizer to create reactive oxygen species which destroys fungal structure	Delivered in combination with methyl-aminolevulinic acid (three sessions, with 15 days interval) or 5-aminolevulinic acid (once a week)	No relapses, no hepatotoxicity, no interactions with drugs.	Teratogenic risks, slight pain, restriction in exposure to direct sunlight or heat for at least 2 days, improper penetration (for which either urea is employed or microabrasion is done).	[35-38]
	Ultrasound	Low frequency ultrasonic waves improve penetration by forming micropores in the nail structure	400 and 600 kHz frequencies and duration of 120 seconds were found most efficient for application	Enhanced and controlled rate of penetration, no systemic side effects.	Complicated device, expert help necessary, costly.	[39-48]