ReviewPotential of solid lipid nanoparticles in brain targeting
Introduction
Delivery of drugs to the brain is a major challenge due to the presence of the blood–brain barrier. Successful delivery across the blood–brain barrier (BBB) has only been achieved in some cases, e.g. through the use of prodrugs. To reach therapeutic drug level in the brain, nanoparticulate systems as drug carriers with sufficiently high loading capacity and small particle size, which can bypass the Reticulo Endothelial System (RES system), are being looked into as suitable delivery systems [1], [2], [3], [4].
Considering the success of these nanoparticles to pass through the BBB and their limitation(s) especially with respect to toxicity and stability, another suitable option for drug delivery into the brain is solid lipid nanoparticles (SLNs). These consist of spherical solid lipid particles in the nanometer range, which are dispersed in water or in aqueous surfactant solution. They have thus a potential to carry lipophilic or hydrophilic drug(s) or diagnostics [5], [6], [7].
Section snippets
Blood–brain barrier (BBB)
The blood–brain barrier (BBB) is the specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. Unlike peripheral capillaries that allow relatively free exchange of substances across/between cells, the BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzymes) barriers [3]. Thus the BBB is often the rate-limiting
Novel drug delivery system approach
Two main reasons for the failure of drug delivery to the brain are:
- 1)
Poor penetration of the drug molecule across the BBB.
- 2)
Back transport (efflux) of drugs from the brain to the blood.
Various colloidal delivery systems have been tried upon by different researchers to overcome, especially the first aspect. These systems include liposomes, microspheres, lipid microspheres, niosomes, nanoparticles, and solid lipid nanoparticles (SLNs) [24], [25], [26], [27], [28], [29].
For a delivery system to be
Analytical methods for characterization
In order to develop a drug product of high quality, a precise physicochemical characterization of the SLNs is necessary. The size of the nanoparticles is the most important feature; however other parameters such as density, molecular weight, and crystallinity influence the nanoparticle release and degradation properties. The in vivo fate vis-à-vis body distribution and interaction with the body environment are however influenced by surface charge, hydrophilicity, and hydrophobicity etc [46].
Dialysis tubing
In vitro drug release could be achieved using dialysis tubing. The solid lipid nanoparticle dispersion is placed in a prewashed dialysis tubing which can be hermetically sealed. The dialysis sac is then dialyzed against a suitable dissolution medium at room temperature, the samples are withdrawn from the dissolution medium at suitable intervals, centrifuged and analyzed for drug content using a suitable analytical method (U.V. spectroscopy, HPLC etc) [5], [57]. The maintenance of sink
Conclusions
SLN delivery can be an innovative way to administer molecules into the brain by possibly overcoming or alleviating the solubility, permeability and toxicity problems associated with the respective drug molecules. This will have an advantage over the conventional invasive methods of drug delivery to the brain. High physical stability of these systems is another advantage. The number of products based on polymeric micro or nanoparticles on the market is limited mainly because of the cytotoxicity
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