*2.9.1 Solid lipid nanoparticle*

Solid lipid nanoparticles (SLN, **Figure 12**) are composed of lipids that are solid at room temperature as well as body temperature and dispersed in water or an aqueous surfactant solution [66]. The lipids that can form SLN can be complex acylglycerol mixtures, highly purified triacylglycerol, or waxes. Extensive research has been performed on the solid lipid nanoparticles for their application in delivering proteins or peptides mainly due to their biocompatibility, biodegradation, and good tolerability [67]. It has been reported that SLN can enhance the bioavailability of the protein or peptide therapeutics and prolong their residence time in blood [68]. SLN can also enhance the oral absorption of many drugs [69, 70]. When SLNs are administered orally, they can be absorbed either through the M-cells (membranous epithelial cells) of the Peyer's patches in the gut-associated lymphoid tissue (GALT) or transcellularly [71].

Surface modification of nanoparticles with chitosan is an excellent way of enhancing the penetration of encapsulated proteins or peptides (e.g., insulin) through mucosal surfaces. This chitosan modified SLN has antimicrobial, mucoadhesive, absorption-enhancing properties and low toxicity in addition to good biocompatibility and biodegradation [72]. Mucoadhesive properties of chitosan may enhance drug uptake due to the longer contact period with the intestinal epithelium. This prolonged contact of the nanoparticle with the intestinal membrane leads to enhanced penetration of the protein or peptide. Also, chitosan is an effective permeability enhancer as it reversibly changes tight junctions [73, 74]. Fonte et al. showed

**Figure 12.** *General structure of solid lipid nanoparticles.*

#### *Protein and Peptide Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.99608*

the ability of the chitosan-coated SLN to enhance the intestinal uptake of insulin by comparing with the uncoated SLN [75]. Significant improvement of hypoglycemic effect was observed for the chitosan-coated SLN compared to the uncoated SLN. Improvement of hypoglycemic effect could be due to mucoadhesive property of chitosan, which not only overcome the degradation of insulin in the GIT, but also promotes intestinal insulin uptake. However, one major limitation of the oral delivery of insulin-loaded nanoparticles is their elimination by the mononuclear phagocyte system [76, 77]. Macrophages present in various tissues such as the liver, spleen and bone marrow are also responsible for eliminating nanoparticles. The use of PEG [78] and other hydrophilic polysaccharides [79] coating to avoid phagocytosis of nanoparticles by macrophages has been reported. SLNs coated with chitosan were not internalized by the murine macrophage cell line, while the uncoated SLN were taken up by these cells [80]. Thus, chitosan was able to provide stealth properties to the SLN.
