Table 1.

Recent Studies Using Different Nano-Based Drug Delivery Systems for Local Anesthetics

Drug Delivery Systems (DDSs)	Carriers	Drugs	Models	Main Effects	Ref.
Polymeric nanoparticle-based DDSs	Alginate/AOT nanoparticles; alginate/chitosan nanoparticles	Bupivacaine	Swiss mice; fibroblasts	To prolong the duration of motor and sensory blockades	[25]
	Alginate/chitosan nanoparticles	Bupivacaine	New Zealand white rabbits; Wistar rats; fibroblasts	To prolong the local anesthetic effect and altered pharmacokinetics	[26]
	Chitosan-GP/PCL polymeric nanocapsules	Bupivacaine	SD rats; fibroblasts	To achieve good biodegradability and biocompatibility	[18]
	PLGA nanoparticles coated with chitosan	Benzocaine	Fibroblasts; keratinocytes	To get a prolonged local anesthetic therapy	[27]
	PLGA nanospheres	Bupivacaine	Fibroblasts	To prolong the anesthetic effect and reduce toxicity	[28]
	PLGA nanospheres	Ropivacaine	Fibroblasts	To improve the stability and decrease toxicity	[29]
	Peptide self-assembled nanofibers	Site-1 sodium channel blockers (S1SCBs)	SD rats; myoblasts; adrenal gland pheochromocytoma cells	To prolong nerve blockade, reduce systemic toxicity, with benign local-tissue reaction	[17]
Lipid nanoparticle- based DDSs	Solid lipid nanoparticles (SLNs)	Dibucaine	Fibroblasts; keratinocytes	To prolong DBC release and reduce its toxicity	[30]
		Benzocaine	Wistar rats; Franz diffusion cells	To improve the intensity and duration of anesthetic effect	[31]
	Nanostructured lipid carriers (NLCs)	Butamben	SD rats	To improve anesthesia at inflamed tissues	[32]
		Lidocaine	SD rats; fibroblasts	To achieve a prolonged and efficient effect	[33]
		Lidocaine	Kunming mice; Franz cells	To enhance the transdermal delivery of lidocaine	[34]
		Bupivacaine	Wistar rats; Franz diffusion cells	To reduce the required dose, and decrease the systemic toxicity	[35]
		Lidocaine; prilocaine	Franz diffusion cells	To achieve the sustained release	[36]
	Lipid-based nanoemulsion	Bupivacaine HCl	Wistar rats	To achieve prolonged local action	[37]
		Eugenol	Patients	To decrease cannulation related pain	[38]
		Lidocaine	Mice	To achieve a higher anesthetic effect	[39]
		15% isoflurane	Dogs	To maintain effective anesthesia	[40]
Inorganic nanoparticle-based DDSs	Gold nanoparticles	Procaine; tetracaine; dibucaine	Not applicable	To characterize the interaction of gold nanoparticles and local anesthetics	[41]
	Silver nanoparticles	Procaine; tetracaine; dibucaine	Not applicable	To characterize the interaction of silver nanoparticles and local anesthetics	[42]
	Zinc oxide nanoparticles	Not applicable	Swiss Albino mice	To attenuate neurogenic and inflammatory pain	[43]
	Magnesium oxide nanoparticles	Ketamine	NMRI strain mice	To induce analgesic and anti-inflammatory effects	[44]
	Gold-coated magnetite nanoparticles	Intrinsic analgesic properties	In vitro human spine model	To concentrate and localize drugs at targeted sites	[45]
	Organosilica nanoparticles	Ropivacaine	Mice; PC12 cells	To get long-lasting pain relief	[46]
	Hollow Silica Nanoparticles	Tetrodotoxin	Rats; C2C12 cells	To enhance the nerve blockade	[47]

Abbreviations: AOT, alginate/bis(2-ethylhexyl) sulfosuccinate; DBC, dibucaine; DDSs, drug delivery systems; HCl, hydrochloric acid; NLCs, nanostructured lipid carriers; PLGA, Poly (lactic-co-glycolic acid); SD, Sprague-Dawley; SLNs, solid lipid nanoparticles; TAT-NLC-LID, transcriptional transactivator peptide modified lidocaine loaded nanostructured lipid carriers; TPGS/LID-NLC, Tocopheryl polyethylene glycol 1000 succinate-modified cationic nanostructured lipid carriers for the delivery of lidocaine.