**Author details**

Bioadhesive poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were reported as promising drug delivery systems [185], and surface modification of nanocarriers was provided by application of mannan-based PE-grafted ligands (MAN-PEs) [186]. Kong et al. investigated MAN-PE-modified bioadhesive PLGA nanoparticles as active targeting gene delivery system using plasmid enhanced green fluorescent protein (*pEGFP*) as the model gene [187]. In the reported study, in order to achieve active targeting to the liver, surface of of PLGA nanopar‐ ticles was modified by the application of MAN-PEs. *In vitro* and *in vivo* behavior of mannanmodified DNA-loaded PLGA nanoparticles were compared with nonmodified DNA-loaded PLGA nanoparticles. Spherical shapes were observed for nonmodified DNA-NPs while the mannan-modified MAN-DNA-NPs had a dark coat on the white balls, that indicated the successful coating of mannan-PE. The mean particle size of NPs was around 100–200 nm, which was ideal for the nanoparticulate system. MAN-PEs-modified *pEGFP*-loaded bioadhesive PLGA-NPs could be targeted to the liver and successfully transfected the Kupffer cells (KCs).

In the study of Wu et al., mannan-PEG-PE (MN-PEG-PE) modified bioadhesive PLGA nanoparticles were obtained as a targeted gene delivery system [188]. Mannan was the target part that bind to the mannose receptor (MR) in the macrophage, and PEG-PE was the spacer linked into the surface of NPs. The results of this study confirmed that mannose-mediated targeting could successfully deliver genes into MR expressing cells. Improved transfection efficiency was observed in the case of mannose containing targeting ligands, such as in DNA loaded PLGA NPs. The results supported the active targeting ability of mannan containing PEG-PE modified bioadhesive PLGA nanoparticles, and the resulting vectors would be very

In the study of Kaur, sustained and targeted release nanoparticles of didanosine were formu‐ lated using gelatin as polymer and mannan-coating to further enhance its macrophage uptake and its distribution in organs that act as major reservoirs of HIV [189]. Coating of nanoparticles with mannan further retarded the drug release (42.5 ± 1.7% over 24 h) and increased the cellular uptake of nanoparticles (N-C3-M) as was evident by higher staining intensity and complete lysis within 2 h of incubation. The better cellular uptake of mannan-coated nanoparticles might be due to the presence of mannosyl receptor predominantly on the macrophage cell surface, which was used by the cells for endocytosis and phagocytosis [190,191]. The results showed higher accumulation of didanosine in brain when administered through mannan-coated nanoparticles. Didanosine is a hydrophilic drug and its ability to cross the blood brain barrier was very low; however, mannan-coated nanoparticles provided enhanced delivery of dida‐ nosine to brain. Hence, mannan-coated gelatin nanoparticles resulted in a significantly higher

Overview of literature clearly shows the high potential of mannan-based biomaterials in health related applications. In these studies though, the monomer composition and structure of mannan polysaccharide plays the key role for a successful design. It is well known that the

useful in gene delivery both *in vitro* and *in vivo.*

326 Application of Nanotechnology in Drug Delivery

concentration of didanosine in spleen, lymph nodes and brain.

**7. Future prospects**

Songul Yasar Yildiz and Ebru Toksoy Oner\*

\*Address all correspondence to: ebru.toksoy@marmara.edu.tr

Industrial Biotechnology and Systems Biology Research Group, Department of Bioengineer‐ ing, Marmara University, Istanbul, Turkey
