9.1.1 Polyethylene glycol (PEG) surface modified solid lipid nanoparticles

Icariin (IRN) is widely used as traditional Chinese medicine for the treatment of kidney diseases and reinforce yang. The PEG surface modified Icariin (IRN) loaded SLNs (PEG-IRN-SLNs) was developed for targeted delivery of IRN to the kidney and to improve the bioavailability. The SLN was prepared by high temperature melt-cool solidification method. Upon comparing with IRN solution it was revealed from the pharmacokinetic study that the biological half-life (t1/2) and area under curve (AUC) of PEG-IRN-SLN was 7-fold and 4-fold higher. Biodistribution study revealed that IRN concentration in kidney tissues was significantly increased. Moreover, the relative target efficiency to kidney tissues was 79% and relative tissue exposure was 16.95. Thus the develop SLN could be helpful in the treatment of kidney diseases [76].

### 9.1.2 Sialic acid conjugated PEGylated solid lipid nanoparticles

E-selectin is a promising target for the site-specific delivery of antiinflammatory agents. Several researchers have reported that sialic acid (SA)-mediated micelles could be specifically internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) via the specific binding between SA and E-selectin receptor [77]. Sialic acid (SIA) conjugated PEGylated dexamethasone (DXM) loaded SLNs (SIA-PEGylated-DXM-SLN) were developed to deliver DXM specifically to the kidney and to improve the therapeutic efficacy of DXM for renal ischemia–reperfusion injury (IRI)-induced acute renal injury. The Sialic acid (SIA) conjugated PEGylated DXM (SIA-PEG-DXM) was synthesized by adding PEG-DXM, dicyclohexylcarbodiimide (DCC), and 4-dimethylaminopyridine (DMAP) into anhydrous dimethyl formamide (DMF) followed by addition of SIA into the solution. The resulting mixture was stirred for obtaining SIA-PEG-DXM. The crude product was purified by dialysis against deionized water for 2 days, followed by lyophilization. The developed SLNs potentially had good colloidal stability in human body. The study revealed that the apoptotic human umbilical vein endothelial cells (HUVECs) were significantly decreased. It indicated the suitability of SIA-PEGylated-SLNs for internalization by the inflamed vascular endothelial cells. Biodistribution study revealed higher renal accumulation of DXM (range 2.7- to 5.88-fold higher) after 6 h of intravenous administration. The Pharmacodynamic study revealed that higher blood biochemical indexes, histopathological changes, oxidative stress levels, and pro-inflammatory cytokines which indicated improved renal function by the influence of SIA-PEGylated DXM [64].

List of SLNs and their different ligand conjugated form targeting to the kidney have been summarized in Table 5.
