Table 3.

Studies on the nasal heparin formulations.

Type of heparin	Formulations	Penetration enhancers	Animal model / Human	Results	Ref.
UFH	Aqueous solution	-	Human	Heparin showed the protection with respect to nasal allergic challenge.	[84]
UFH	Aqueous solution	-	Human	Nasal heparin showed a protective role against AMP provocation by inhibition of mast cell activation.	[85]
UFH	Poly(L-lactic acid) microspheres	-	Rats	Nasal application of poly (L-lactic acid)-heparin microspheres had a relative bioavailability of 143% (vs nasal heparin solution).	[86]
UFH	Chitosan nanoparticles	carboxymethyl-β-cyclodextrin	-	Heparin was released slowly from chitosan/cyclodextrin nanoparticles (8.3-9.1% heparin within 8 h).	[59]
Enoxaparin Dalteparin UFH	Aqueous solution	Tetradecymaltoside	Rats	The addition of tetradecymaltoside into nose drops formulations containing LMWH has let to in a significant increase in the Cmax and AUC of anti-factor Xa activity compare to LMWH in saline. But the addition of tetradecymaltoside into formulations containing UFH has let to much smaller increase in the Cmax and AUC of anti factor Xa activity.	[87]
LMWH	Aqueous solution	Dimethyl-β-cyclodextrin	Rats	Dimethyl-β-cyclodextrin was found the most effective enhancer for the absorption of LMWH.	[88]
LMWH (Enoxaparin)	Aqueous solution	Alkylmaltosides	Rats	Alkylmaltosides improved the nasal absorption of LMWH without causing an irreversible damage in nasal mucosa. When the alkyl chains of maltosides were increased from 8 to 14 carbons, absolute and relative bioavailability of Enoxaparin were increased by two-fold.	[89]
LMWH (Enoxaparin)	Aqueous solution	Alkonoylsucroses	Rats	The enhancers increased the bioavailability of LMWH when compared to saline solution. The potency of these enhancers was dependent on their hydrophobic chain lengths.	[90]

UFH = Unfractionated heparin; LMWH = Low molecular weight heparin.