Targeting of small or biopharmaceutical anti-inflammatory drugs to inflamed bowel disease by nanocarriers
(2013)
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- Authors
- Supervisors
- Préat, Véronique
- Abstract
- Inflammatory bowel diseases are relapsing and chronic inflammatory disorders of the gut. Although most of the conventional anti-inflammatory agents can be administered orally, non-specific delivery of these drugs is observed, leading to systemic toxicity associated with serious adverse effects. The development of drug delivery systems able to specifically target and to deliver anti-inflammatory drugs to inflamed colonic areas of the colon is of great interest. It should lead to higher local concentrations and maintain therapeutic efficacy while enhancing safety by decreasing non-specific delivery. Use of nanocarriers for this purpose seems promising as they showed a preferential uptake in inflamed areas. Hence, the aim of this thesis was to encapsulate small drugs (budesonide and curcumin) and biopharmaceutics (ovalbumin as model drug and anti-TNF-α fragment antibody) in various nanocarriers: polymeric nanoparticles, nano-structured lipid carriers and self-nanoemulsifying drug delivery systems. Various delivery strategies were assessed: pH-sensitivity, mucoadhesion, sustained release, active targeting and lipid-based delivery. The potential of these nanoparticulate drug delivery systems for inflamed colon-specific topical targeting and delivery was evaluated in in vitro, ex vivo and in vivo models. Firstly, we have demonstrated the efficacy of nanostructured lipid carriers for the topical delivery of budesonide in inflamed colon using. Secondly, we compared the topical delivery of curcumin, showing that a nanoscale delivery strategy using pH-sensitive and sustained release nanoparticles gives better in vivo results than the other nanoscale delivery strategy using self-nanoemulsifying drug delivery systems. Thirdly, using ovalbumin as model drug, we have compared several strategies to target the inflamed colon using polymeric nanoparticles as biopharmaceutical drug carrier. Exploiting the ability of design of polymeric nanoparticles, we have demonstrated that active targeting of macrophages and dendritic cells leads to a preferential accumulation in inflamed areas. Finally, we formulated 2 types of polymeric nanoparticles encapsulating an active biopharmaceutical agent possessing features suitable for the inflamed colon delivery.
- Affiliations
Citations
Coco, R. (2013). Targeting of small or biopharmaceutical anti-inflammatory drugs to inflamed bowel disease by nanocarriers. https://hdl.handle.net/2078.5/25929