ABSTRACT
Keywords: solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanopharmaceutical, targeting, stealth nanoparticles, particle size, particle charge, surface modification, cancer treatment, gene therapy, anti-cancer drugs, genes, non-steroidal anti-inflammatory drugs (NSAIDs), polyethylene glycol (PEG), pegylation, chitosan
of entrapped actives by improving their tissue distribution, and targeting of drugs are provided by employing SLN and NLC in various administration routes such as parenteral [5], ophthalmic [6], nasal [7], pulmonary [8], transdermal [4], and oral [9]. At the site of action with low systemic level and selective uptake of the drug by the target organ are great achievements in order to obtain ideal drug delivery by systemic application such as parenteral. Various research groups have focused on the targeting of lipid nanoparticles for primarily delivery of antineoplastic agents and biotechnological materials in the last decade, since the site
delivery of those actives provides great benefits in the treatment of cancer and illness caused by genetic disorders [10, 11]. SLN and NLC are sophisticated systems for actives at cellular level. Thus, the incorporation of genetic materials such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and oligonucleotides into lipid nanoparticles introduces a pathway for gene transfer to cells. This makes solid lipid-based drug carrier systems one of the most attractive systems for site-specific targeting primarily via parenteral application.The safety of drug carrier systems is another important subject for researchers in addition to the great challenge for formulating sophisticated drug carrier systems. Nanoparticle-based synthetic and/or semisynthetic polymers, or contained residuals from organic solvents, often result in toxic or immunological side effects. However, lipids and surfactants used as components of SLN and NLC have been approved as “Generally Recognized as Safe” (GRAS status) due to their low toxicity. They have been using as excipients in pharmaceuticals and cosmetics for years [12]. SLN and NLC are 10-100-fold less cytotoxic than their polymeric counterparts since they do not contain residues typical for polymeric carriers like cytotoxic monomers, polymerization accelerators, etc. [13]. They are also safe and compatible with the environment. One can avoid the use of organic solvents, and surface-active agents at high concentrations by high-pressure homogenization, membrane contactor method, liquid flow-focusing using microchannels or microtubes, and supercritical fluid technology. In addition, excellent reproducibility with these cost-effective techniques, which are suitable for scaling-up, has been reported [14, 15]. Various drug incorporation methods have also been reported for years (e.g., preparation via O/W microemulsion and double (W/O/W)
emulsion, solvent emulsification-evaporation or -diffusion, and high shear homogenization and/or ultrasonication) [16].Successfully formulated SLN and NLC can be stable for up to three years, which is of great importance with respect to colloidal drug carrier systems [13, 17]. They can be produced in desired size ranges, whereas liposomes are very often difficult to produce in a specific size range and with a sufficient drug payload. They have relatively low transfection rates to cells. Fast release of hydrophobic drugs and their instability are also emerging difficulties of liposomes [18].
