Biodistribution of Stealth and Non-stealth Solid Lipid Nanospheres after Intravenous Administration to Rats

Abstract

Drug-free stealth and non-stealth solid lipid nanospheres (SLNs) were administered intravenously to rats to evaluate their tissue distribution and their transport across the blood-brain barrier. Two types of experiments were performed using unlabelled and labelled SLNs. Rats were administered labelled non-stealth or stealth nanospheres (NSSLNs and SSLNs) and their tissue distribution was monitored for 60 min. In another experiment, rats were injected with unlabelled NSSLNs or SSLNs and the cerebrospinal fluid (CSF) was analysed using transmission electron microscopy (TEM) to confirm the presence of the SLNs. Some differences were found in the biodistribution between labelled NSSLNs and SSLNs. In particular, the radioactivity in the liver and the lung was much lower for SSLNs than for NSSLNs, confirming a difference in their uptake. Both types of SLNs were detected in the brain. TEM analysis showed both types of SLNs in rat CSF.

Pharmacokinetics and Tissue Distribution of Idarubicin-Loaded Solid Lipid Nanoparticles After Duodenal Administration to Rats

“…Many possible mechanisms of nanoparticle‐mediated drug transport to the brain are reported by Kreuter,37 such as an increased retention of nanoparticles in the brain blood capillaries, higher concentration gradient, and endocytosis or the transcytosis of the nanoparticles. In our study the presence of idarubicin and idarubicinol in the brain after duodenal administration is significant and confirms previous results obtained with labeled SLN 38. In other research on another anthracycline, doxorubicin incorporated in SLN and administered iv to rats39 was recovered in the brain together with its main metabolite, doxorubicinol.…”

Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

“…Since these organs are HIV targets, SLNs have potentials to be applicable to the targeted treatment of HIV. Similarly, other studies using rat models have demonstrated that both stealth and non-stealth stearic acid labeled SLNs could access the liver, lung and brain tissues [101], with stealth SLNs exhibiting significantly improved drug accumulation when compared to non-stealth SLNs [98]. In general, many excipients for SLN, including poloxamer 188 stabilized stearic acid [102], emulsifying wax/Brij ® 78, and Brij ® 2/Tween 80 SLNs [103] and targeting ligands have been used to achieve brain and other tissue specific targeting [104].…”

Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats

“…However, specific receptors allowed the transport of endogenous compounds across the BBB [42]. Studies[25,40,41,43] have revealed the permeability of polysorbate 80‐coated NPs across the BBB, and the possible mechanisms[44] may be that (1) the endocytosis of NPs by the BCECs[43,45] makes the drug release within these cells and leads to the following drug diffusion in brain parenchyma; (2) the transcytosis of NPs releases the bound drugs directly into the brain parenchyma;[46,47] (3) the increased retention of NPs in the brain blood capillaries combined with an adsorption to the capillary walls creates a higher concentration gradient, thus enhancing the transport across the endothelial cell layer and leading to drug accumulation in the brain;[48] and (4) polysorbate 80 can inhibit the efflux of P‐gp in the BCECs and enhance drug distribution in brain;[49] and (5) polysorbate 80‐coated NPs can adsorb apolipoprotein B/E after injection into the bloodstream, which plays an important role in the transport of low‐density lipoprotein (LDL) into brain [50]. After apolipoprotein B/E being bound to the surface, the NPs mimicked the LDL particles to interact with the LDL receptors on the BCECs, then uptaken by the cells via the receptor‐mediated endocytosis.…”