# Recent Advances in Nanoparticle-Mediated Treatment of Inflammatory Bowel Diseases
## 14 Adenovirus-Directed Administration by Enema and Nanoparticle Administration by Gavage  
In an attempt to deliver intestinal epithelial prohibitin 1 (PHB) to the inflamed colon, [PERSON] et al. loaded PHB into nanoparticles and delivered the drug to the site of inflammation using an experimental model of colitis [32]. The anti-inflammatory efficiency of the system was assessed using two different means of administration: adenovirus-directed administration by enema and nanoparticle administration by gavage.  
Overexpression of PHB levels in transgenic mice under the control of the intestinal epithelial-specific promoter attenuated disease severity and NF-kB activation, PHB behaving as both an anti-oxidant and anti-inflammatory agent.  
The two delivery options used to overexpress PHB in colonic epithelial cells showed decreased expression of PHB during active inflammation. The adenovirus-directed administration by enema was employed as a proof of concept to determine the therapeutic efficacy of PHB. PHB-loaded nanoparticles were employed to determine their benefits for the treatment of IBD in human subjects. They both showed higher PHB levels in surface colonic epithelial cells and attenuated disease severity in DSS-induced colitis mouse models as indicated by body weight loss, clinical score, MPO activity, expression of pro-inflammatory cytokines, histological score, and protein oxidation.  
5-aminosalicylic acid-loaded silicon dioxide nanoparticles (5-ASA-SiO2 NPs).  
Silicon dioxide nanoparticles have been designed and prepared as selective drug release systems that target the inflamed colon [33]. Methyl-5-ASA silicon dioxide nanoparticles (Me5 ASA-SiNPs) incorporate both the advantages of passive drug targeting by nanoparticles and controlled release at a targeted site of prodrugs to achieve preferential accumulation at the site of inflammation. Covalent binding was obtained via a four-step mechanism. Appropriate cell lines were used to assess whether the modified conjugates exhibit toxicity in vitro and mice with pre-existing colitis were employed to evaluate drug targeting index and therapeutic efficacy. Modified nanoparticles had a final diameter of about 140 nm. In vitro drug release tests proved efficient and prolonged drug retention in the nanoparticle core.  
Silicon nanoparticles (SiNPs) are novel site-targeted drug-delivery vehicles used in IBD providing selective drug targeting and drug release to the site of inflammation, thus improving therapeutic efficacy.  
The 5-ASA was covalently bound to the matrix polymer poly(\(\epsilon\)-caprolactone) to prevent premature release of loaded drug, which may occur when using conventional physicochemical encapsulation techniques [34]. Feasibility studies based on two preparation methods and cell-culture toxicity testing were then carried out. The emulsification and the nanoprecipitation methods were used for the production of nanoparticles in the size range of 200-350 nm.  
In vitro release testing demonstrated that the drug was specifically confined within the nano-matrix, thus achieving optimal targeting efficiency into the colon. Polymer linkages did not determine major changes. The mitigating effect of the Me5 ASA NP was considerable in mouse experimental colitis, improving selectivity in terms of drug administration and reducing premature drug release following oral administration.  
Therapeutic efficacy was further assessed in vivo using a mouse model of experimental colitis, the nanocomposites proving their usefulness in considerably reducing the dose required to achieve therapeutic efficacy [34].