**6. Nanotechnology-based drug delivery systems**

Perfectly, nanoparticulate drug delivery system should selectively accumulate in the necessary organ or tissue and at the same time, penetrate target cells to deliver the bioactive agent [48]. It has been proposed that, organ or tissue accumulation could be achieved by the passive or antibody-mediated active targeting, while the intracellular delivery could be mediated by specified ligands or by cell-penetrating peptides [49-53]. The purpose of drug delivery is to carry out sustained (or slow) and/or controlled drug release and therefore to improve efficacy, safety, and/or patient comfort [54]. Thus, the use of drug delivery systems has been suggested for passive targeting of infected cells of the mononuclear phagocytic system to enhance the therapeutic index of antimicrobials in the intracellular environment, while minimizing the side effects related with the systemic administration of the antibiotic [55]. These systems propose many advantages in drug delivery, mainly focusing on improved safety and efficacy of the drugs, e.g. providing targeted delivery of drugs, improving bioavailability, extending drug or gene effect in target tissue, and improving the stability of therapeutic agents against chemical/ enzymatic degradation [56]. The nanoscale size of these delivery systems is the basis for all these advantages [57]. It is therefore assumed that, DDS with enhanced targeting property is highly promising in increasing the efficiency and efficacy of therapy while at the same time minimizing side effects [33].

nanoparticles have been repeatedly ornamented with lectin, which is a protein that binds to simple or complex carbohydrates present on most bacterial cell walls. For example, lectinconjugated gliadin nanoparticles were studied for treating *Helicobacter pylori* related infection diseases. It has been found that lectin-conjugated nanoparticles bind specially to carbohydrate receptors on cell walls of *H. pylori* and release antimicrobial agents into the bacteria [30, 67]. Rifampicin-loaded polybutylcyanoacrylate nanoparticles have also shown enhanced antibac‐ terial activity both *in vitro* and *in vivo* against *S. aureus* and *Mycobacterium avium* due to an

Nanoparticle based Drug Delivery Systems for Treatment of Infectious Diseases

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A hydrogel is a network of hydrophilic polymers that can swell in water and hold a large amount of water while maintaining the structure [69]. Drugs can be loaded into the polymer matrix of these materials and controlled release is dependent on the diffusion coefficient of the drug across the hydrogel network [70]. Amongst the several types of drug delivery systems that have been developed in order to improve effectiveness and biocompatibility, hydrogels are extremely promising. Hydrogels are biocompatible hydrophilic networks that can be constructed from both synthetic and natural materials [71]. In an overall view, hydrogels can be classified based on a variety of characteristics, containing the nature of side groups (neutral or ionic), mechanical and structural features (affine or phantom), method of preparation (homo-or co-polymer), physical structure (amorphous, semicrystalline, hydrogen bonded, supermolecular, and hydrocollodial), and responsiveness to physiologic environment stimuli (pH, ionic strength, temperature, electromagnetic radiation, etc.) [72-75]. Classically, hydro‐ gels have been used to deliver hydrophilic, small-molecule drugs which have high solubilities in both the hydrophilic hydrogel matrix and the aqueous solvent swelling the hydrogel [76]. Hydrogel-based hydrophobic drug delivery is in many respects a more difficult problem given the innate incongruity of the hydrophilic hydrogel network and the hydrophobic drug. A variety of strategies for introducing hydrophobic domains directly into otherwise hydrophilic hydrogel networks have permitted significant improvements in the loading of hydrophobic drugs [76]. Hydrogel/glass composite (Nitric oxide-releasing nanoparticles) NO NPs have also been shown to have a high degree of effectiveness against (Methicillin-resistant *Staphylococcus aureus*) MRSA infection in several different mouse models. In one mouse study by Martinez et al., administration of topical hydrogel/glass composite NO NPs into skin wounds infected with MRSA reduced bacterial burden significantly compared to controls [77]. Despite these many advantageous properties, hydrogels also have several limitations. The low elastic force of many hydrogels limits their use in load-bearing applications and can result in the precocious decomposition or flow away of the hydrogel from a targeted local site. This limitation may not be important in many typical drug delivery applications (e.g. subcutaneous injection) [78].

Metal-based nanoparticles of different shapes, sizes (between 10 to 100 nm) have also been investigated as diagnostic and drug delivery systems. Most common metallic nanoparticles contain gold, nickel, silver, iron oxide, zinc oxide, gadolinium, and titanium dioxide particles

effective delivery of drugs to macrophages [68].

**7.2. Hydrogels**

**7.3. Metal nanoparticles**
