Solid lipid nanoparticle
The conventional approaches such as use of permeation enhancers, surface modification, prodrug synthesis, complex formation and colloidal lipid carrier based strategies have been developed for the delivery of drugs to intestinal lymphatics. In addition, polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions, micellar solutions and recently solid lipid nanoparticles (SLN) have been exploited as probable possibilities as carriers for oral intestinal lymphatic delivery.
A solid lipid nanoparticle is typically spherical with an average diameter between 10 and 1000 nanometers. Solid lipid nanoparticles possess a solid lipid core matrix that can solubilize lipophilic molecules. The lipid core is stabilized by surfactants (emulsifiers). The term lipid is used here in a broader sense and includes triglycerides (e.g. tristearin), diglycerides (e.g. glycerol bahenate), monoglycerides (e.g. glycerol monostearate), fatty acids (e.g. stearic acid), steroids (e.g. cholesterol), and waxes (e.g. cetyl palmitate). All classes of emulsifiers (with respect to charge and molecular weight) have been used to stabilize the lipid dispersion. It has been found that the combination of emulsifiers might prevent particle agglomeration more efficiently.
Development of solid lipid nanoparticles is one of the emerging fields of lipid nanotechnology (for a review on lipid nanotechnology, see ) with several potential applications in drug delivery, clinical medicine and research, as well as in other discipline. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could hold great promise for attaining the bioavailability enhancement along with controlled and site specific drug delivery. SLN's are also considered to well tolerated in general, due to their composition from physiologically similar lipids.
Use for drug delivery
Solid lipid nanoparticles have recently materialized as a novel approach to oral and parenteral drug delivery systems. SLNs combine the advantages of lipid emulsion and polymeric nanoparticle systems while overcoming the temporal and in vivo stability issues that troubles the conventional as well as polymeric nanoparticles drug delivery approaches (Mehnert et al., 2001). It has been proposed that SLNs combine numerous advantages over the other colloidal carriers i.e. incorporation of lipophilic and hydrophilic drugs feasible, no biotoxicity of the carrier, avoidance of organic solvents, possibility of controlled drug release and drug targeting, increased drug stability and no problems with respect to large scale production. A recent study has demonstrated the use of solid lipid nanoparticles as a platform for oral delivery of the nutrient mineral iron, by incorporating the hydrophilic molecule ferrous sulphate (FeSO4) in a lipid matrix composed of stearic acid. Carvedilol-loaded solid lipid nanoparticles were prepared using hot-homogenization technique for oral delivery using compritol and poloxamer 188 as a lipid and surfactant, respectively. Another example of drug delivery using SLN would be oral solid SLN suspended in distilled water, which was synthesized to trap drugs within the SLN structure. Upon indigestion, the SLNs are exposed to gastric and intestinal acids that dissolve the SLNs and release the drugs into the system.
Solid lipid nanoparticles and its potential lymphatic absorption mechanism
Elucidation of intestinal lymphatic absorption mechanism from solid lipid nanoparticles using Caco-2 cell line as in vitro model was developed. Several researchers have shown the enhancement of oral bioavailibility of poorly water soluble drugs when encapsulated in solid lipid nanoparticle. This enhanced bioavailibility is achieved via lymphatic delivery. To elucidate the absorption mechanism, from solid lipid nanoparticle, human excised Caco-2 cell monolayer could be alternative tissue for development of an in-vitro model to be used as a screening tool before animal studies are undertaken. The results obtained in this model suggested that the main absorption mechanism of carvedilol loaded solid lipid nanoparticle could be endocytosis and, more specifically, clathrin-mediated endocytosis. 
Characteristics and production
An SLN is generally spherical in shape and consists of a solid lipid core stabilized by a surfactant. The core lipids can be fatty acids, acylglycerols, waxes, and mixtures of these surfactants. Biological membrane lipids such as phospholipids, sphingomyelins, bile salts (sodium taurocholate), and sterols (cholesterol) are utilized as stabilizers. Biological lipids having minimum carrier cytotoxicity and the solid state of the lipid permit better controlled drug release due to increased mass transfer resistance. Shah et al in their book Lipid Nanoparticles: Production, Characterisation and Stability discuss these in details.
Advantages of SLNs are the use of physiological lipids, the avoidance of organic solvents, a potential wide application spectrum (dermal, per os, intravenous) and the high pressure homogenization as an established production method. Additionally, improved bioavailability, protection of sensitive drug molecules from the outer environment water, light) and even controlled release characteristics were claimed by incorporation of poorly water-soluble drugs in the solid lipid matrix.
Nanotechnology and ocular drug delivery
Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. SLNs have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. Solid lipid nanoparticles have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations.
- Nanomedicine, the general field
- Micelle, lipid cored
- Liposome, lipid bilayer shell, an earlier form with some limitations
- Targeted drug delivery
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- Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration
- Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid nanoparticles using Caco-2 cell line as an in-vitro model