Table 1.

Summary of main components, characteristics, methods of manufacture, and advantages and disadvantages of lipid-based nanosystems.

System	Components	Diameter (nm)/Shape	Manufacturing	Pros	Cons	Refs.
Transferosomes	Edge activators, phospholipids	Less than 300/spherical bilayer	Vortexing, sonication, rotary film, or reverse-phase evaporations	Good stability, higher penetration	Susceptible to oxidative degradation	[36,90]
Liposomes	Cholesterol, phospholipids, essential oils	10–1000/spherical bilayers	Solvent dispersion, mechanical dispersion, detergent removal	Controlled release, drug protection, solubility improvement for hydrophobic drugs, high biodistribution and bioavailability	Rigid structure, limited penetration across the stratum corneum	[28,29,32,33,62,90]
Nanostructured lipid carriers (NLCs)	Liquid and solid lipids, surfactants	50–1000/spherical single layer	Sonication, micro emulsification, high-pressure homogenization	High cell uptake, appropriate protection of therapeutics in acidic pH, biodegradable and biocompatible, simplicity of drug entrapment, long shelf-life, more sustainable drug dissolution, high payload, reduced loss of drug during storage	Solid/liquid lipid ratio optimization difficulties	[52,53,91,92,93]
Solid lipid nanoparticles (SLNs)	Surfactants, solid lipids	50–1000/spherical single layer	Sonication, micro emulsification, high-pressure homogenization	High cell uptake, appropriate protection of therapeutics in acidic pH, biodegradable and biocompatible ingredients, simplicity of drug entrapment, long shelf-life	Gelling tendency	[50,51,52,91,92,93,94,95,96,97,98]
Ethosomes	Phospholipids, edge activator, high concentration of a low-molecular-weight alcohol (ethanol ≤45% w/w), water	<200 or 300/spherical with diverse lamellarities	Solvent dispersion, ethanol injection–sonication, thin-film hydration, reverse-phase evaporation, transmembrane pH gradient, extrusion, and sonication	Increased efficacy and therapeutic index, reduce toxicity of API, improved permeation, entrapment of lipophilic, hydrophilic, and amphiphilic agents, simplicity of manufacturing, noninvasive, better solubility and stability, selective passive targeting	Low production yield, only for potent drugs, skin dermatitis or irritation may occur, drug leakage during transfer from organic to water media	[99,100]
Cochleates	Phospholipid–cation precipitates (formed by a continuous, solid, lipid bilayer sheet rolled up in a spiral)	100–1000/cylindrical shape	Trapping method (a bridging agent is mixed with an aqueous lipid suspension), hydrogel method, dialysis, emulsification–lyophilization, microfluidic method, solvent injection	Nonimmunogenic, noninflammatory, and nontoxic, a stable structure due to their tightly packed nature, less susceptible to oxidation of both the encapsulated drug and the phospholipids, sustained release is achievable, enhanced shelf-life, improvements in oral bioavailability of drugs	Aggregation on storage, high production cost	[56,101]