5.1 Solid lipid nanoparticles for active targeting

Baicalin (BCL), a natural product obtained from Scutellaria baicalensis (Family: Labiatae) popularly used in the treatment of Hepatitis-B and liver fibrosis. BCL loaded SLNs were developed. The prepared SLNs were stable and were able to enhance the therapeutic efficacy of BCL by improving its biodistribution in the liver. In vivo biodistribution, targeting evaluation and in vitro anti-oxidant study reveals that the developed BCL-SLNs have substantial liver targeting, improved anti oxidative and hydroxyl radical scavenging abilities [44].

Ficus benjamina (Family: Moraceae) is rich in phenolic (chlorogenic, pcoumaric, ferulic and syringic acids) and total flavonoid content that are effective against chronic alcoholism induced fatal liver and cardio-renal injury. Ethanolic extract of Ficus benjamina (FB) loaded in SLNs (FBSLNs) helped in bioaccumulation of the phenolic and flavonoid content in the liver due to lipophilic nature of SLNs. In vivo evaluation of FBSLNs against hepatic and cardio-renal injury revealed its hepatoprotective activity which was further evident from various biological parameters and histopathological photomicrography. In the liver, accumulation of aldehyde level was reduced that validated the detoxifying nature of FBSLN. Moreover, restoration of aberrant cardio-renal biomarkers and histological consequences revealed the cardio-renal protective potential of FBSLNs [45].

Berberine (BBR), an active constituent of Coptis chinensis (Family: Ranunculaceae) have potential pharmacological effects on type-2 diabetes. It has already been validated that BBR enhances glucose and lipid metabolism through the activation of adenosine monophosphate-activated protein kinase (AMPK) and improve insulin sensitivity. BBR loaded SLNs (BBR-SLNs) were developed to improve the beneficial effect of BBR on hepatosteatosis. The effect of BBR-SLNs on lipid metabolism were studied which revealed gaining of body weight and reduction in liver weight with simultaneous reduction of serum alanine transaminase and liver triglyceride level. Biodistribution study reported 20-fold increase in the concentration of drug in the liver than that of blood. Moreover, it reduced the accumulation of fat and lipid droplet size. It was also noticed that the expression of lipogenic genes was down-regulated and lipolytic gene was up-regulated in BBR-SLNs treated livers which could be helpful in the treatment of hepatosteatosis [46].

model. Biodistribution study revealed site-specific delivery and accumulation of

5.3.1 Polyethylene glycol conjugated (PEGylated) solid lipid nanoparticles for passive

5.3.2 Galactosylated lipid [N-hexadecyl lactobionamide] conjugated solid lipid

recognize terminal b-D-galactose or N-acetylgalactosamine residues. The Nhexadecyl lactobionamide (N-HLBA) was synthesized via an amide bond between the amine group of hexadecylamine and the carboxyl group of lactobionic acid. The

The parenchymal cells of the liver contain asialoglycoprotein receptors which

PEGylated SLNs are reported to be preferentially accumulated in the liver as the kidney is unable to clear the same. Thus, in liver disorders, liver targeting strategy using PEGylation technique is used for delivering numerous drugs. Paclitaxel (PTX) loaded PEGylated SLNs were successfully developed for targeting the liver, in the case of hepatic carcinoma. The cellular uptake study revealed that PTX loaded PEGylated SLNs showed prolonged circulation time in plasma and higher bioaccumulation of drug in the liver when compared with the PTX solution [51]. The preferential drug targeting ability of PEGylated SLNs to cancer cells have

siRNA loaded cSLNs to the liver tissues [50].

DOI: http://dx.doi.org/10.5772/intechopen.88268

targeting

been shown in Figure 2.

nanoparticles

Figure 2.

107

PEGylated SLN in targeting preferentially to cancer cells.

5.3 Solid lipid nanoparticles for passive targeting

Solid Lipid Based Nano-particulate Formulations in Drug Targeting

Cisplatin (CSPT) is an anti-cancer drug which is used in the treatment of many malignancies including hepatocellular carcinoma, lungs carcinoma, etc. The CSPT loaded SLNs (CSPT-SLNs) were successfully developed and were stable in terms of drug content after storage for 3 months in different temperature and humid conditions. In vivo tissue distribution study revealed that the developed CSPT-SLNs were able to deliver a higher amount of CSPT particularly to the liver as compared to the brain, lungs, and kidney [47].

Sorafenib (SFB), a potent multi-kinase inhibitor possess anti-tumor angiogenesis effect (block vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGFR)) and is preferentially used in the treatment of hepatocellular carcinoma. The SFB loaded SLNs (SFB-SLNs) were developed with an objective of improving bioavailability and reducing adverse effects. The results of the stability test showed that SRF-SLNs remained stable for more than 1 month at room temperature. In vivo study of SFB-SLNs revealed improved bioavailability (increased by 66.7%) with remarkably higher bioaccumulation of drug in the liver (2.20-fold higher drug selectivity index value) when compared with the SFB suspension [48].

Primaquine phosphate (PP) is an antimalarial drug that acts on the primary tissue forms of the Plasmodium which after growth within the liver, initiate the erythrocytic stage. Thus, PP loaded SLNs (PP-SLNs) were developed with an aim to deliver liver schizonticide PP directly to the hepatocytes. Stability of the PP-SLNs in suspension was tested for a period of 3 months in terms of size, poly-dispersity, ζ-potential, and pH. There were no noteworthy changes in size, poly-dispersity, ζ-potential, or pH occurred over time. In vivo study report revealed that the developed SLNs were highly effective (>20%) against hypnozoites/liver stage of all malarial species with a reduced dose when compared with the conventional oral dose [49].
