Table 3. Most recent research work done on novel drug delivery strategies for treating onychomycosis.

Category	Year	Novel Formulation	Main Techniques/ Studies	Key Findings	Advantages	References
Nanoparticles	2018	Ketoconazole-encapsulated crosslinked fluorescent supramolecular nanoparticles	Ratiometric mixing, in vivo fluorescent imaging, high-performance liquid chromatography, matrix-assisted laser desorption/ ionization mass spectrometry imaging, histology, mouse model, tattoo based delivery.	The nanoparticles showed high encapsulation efficiency, appropriate fluorescence, sustained release and intradermal retention.	Less invasive, localized and controlled release, dodges systemic side effects, can be applied to other diseases as well.	[1]
Nanoparticles	2018	tioconazole-loaded polymeric nanocapsules	Ultrafiltration-centrifugation, in vitro release and in vitro permeation tests, nail poration, laser scanning confocal microscopy, photon fluorescence, Raman scattering imaging, confocal microscopy.	3 formulations- lacquer, nanocapsule and film were prepared and characterized, almost 100% encapsulation efficiency, were stable, consistent release profile, nail poration provided no leverage, localized therapy observed through Nile Red.	Prolonged release, efficient delivery, greater drug payload, greater penetration.	[2]
Nanoparticles	2017	Voriconazole-loaded nanostructured lipid carriers (NLC)	HPLC, hydration studies, nanoparticles characterization, stability studies, in vitro studies with porcine hooves, statistical analysis.	Maximum penetration was obtained with Urea as enhancer, drug release was 78- 86%, formulations were stable, the release kinetics fitted Higuchi model.	Deeper nail penetration, controlled release.	[3]
Nanoparticles	2017	tioconazole Pullulan nanobased nail formulation	Nanocapsule characterization, morphological analysis, Ultrafiltration-centrifugation, in vitro release studies, bio adhesion assays, antifungal study, irritant potential through Hen's Egg Test - Chorio allantoic Membrane method.	Homogenous nanoparticles, Newtonian properties, release was bi- exponential, better antifungal activity against C.albicans, less irritant potential.	A hydrating formulation so increases permeation easily, better efficacy and deeper nail permeation.	[4]
Nanoparticles	2016	Terbinafine loaded nanobased spanlastic vesicular carriers (nanovesicles)	Ethanol injection method, in vitro release studies, 24 full factorial design, Differential Scanning Calorimetry, X-ray Diffractometry, ex vivo permeation, nail pulverization.	Entrapment efficiency was 8 to 80%, sonication reduce particle size, amorphous, particles were unilamellar and spherical, better drug retention, more drug distribution and deeper nail penetration.	Better drug release and nail penetration.	[5]
Nanoparticles	2016	Ketoconazole loaded nanoemulgel with penetration enhancer	Ultra-performance liquid chromatography (UPLC), Aqueous titration, high-pressure homogenization (HPH), Stress-Stability Studies, Nanoparticle characterization, nanoemulgel evaluation studies, in vitro release, tranungual permeation, antifungal activity and histo pathological studies.	Optimized mean droplet size range: 63- 126nm, No phase separation or flocculation occurred, non-Newtonian, pseudo-plastic nature, maximum drug release was approx. 98%, better antifungal activity than drug solution.	Less toxicity and irritant potential, kinetically stable, safe and effective.	[6]
Spanlastic	2017	Terbinafine loaded spanlastics delivered through novel dosage forms- in situ gels and nail lacquer	Ethanol injection method, characterization studies, in vitro drug release, 23 full factorial experimental design, ex vivo nail permeation studies.	Drug permeation was obtained in the order: In situ gel> nail lacquer>marketed product.	Greater efficacy, patient compliance, more coverage, no irritation.	[7]
Nail lacquer	2017	Terbinafine delivery via liposome-loaded nail lacquer	Thin film hydration technique, quality by design (QbD) technique, liposomes characterization, In Vitro Drug Release, Lyophilization, characterization of liposome loaded nail lacquer, In Vitro drug permeation, antifungal activity.	Drug permeation was more with liposome loaded nail lacquer than with simple nail lacquer, same antifungal activity as of drug solution, formulations passed all evaluation tests.	Enhanced permeation and more therapeutics efficacy.	[8]
Nail lacquer	2017	Ciclopirox-Based Eudragit RLPO Nail Lacquer	Penetration enhancers screening, 33 full factorial design, Physicochemical characterization, in vitro release study, ex vivo nail permeation, Confocal Laser Scanning Microscopy.	Endopeptidase enzyme was selected as penetration enhancer, better permeation than marketed lacquer, better drug diffusion.	Enhanced permeation, non- invasive, localized therapy.	[9]
Nail lacquer	2017	Terbinafine in polyurethane nail lacquer	Quasi-pre-polymerization method, Fourier Transform Infrared Spectroscopy (FTIR), In vitro cytotoxicity assay, Determination of wettability, In vitro adhesion test, in vitro release study, in vitro antifungal activity, positron annihilation lifetime (PAL) measurement.	Contact angle< 90°, no cytotoxicity, better adhesion, lower MIC value, better in vitro drug release.	Biocompatible lacquers, Better drug diffusion, hydrophilic nature, nail adhesion.	[10]
Polymeric films	2016	Polymeric films as novel dosage form for onychomycosis	Carboxy methyl cellulose sodium salt (Sod CMC), Chitosan, 2-Hydroxy ethyl cellulose (HEC), (Hydroxy propyl)methyl cellulose (HPMC), Polyvinyl pyrrolidone (PVP), Propylene glycol (PPG) were the polymers used for making films, film characterization, irritation studies, microscopic studies, adhesive studies.	Dry and non-sticky films, no irritation, HEC and HPMC showed swelling, the polymeric films showed stability, flexibility, water resistance and adhesiveness.	Non- invasive, suitable for nail application.	[11]