Design and development of polymeric nanoparticles as delivery systems for anti-inflammatory drugs

Polymers are malleable materials that offer multiple design possibilities, and as such, they are frequently used to fabricate highly customized nanocarriers for drug delivery applications. Among the most crucial technological advantages of polymer-based drug delivery systems are: (i) They can be engineered to encapsulate a range of different drugs (e.g., small molecules, macromolecules, peptides), (ii) they are generally biocompatible and can be (bio)degradable, (iii) they can reduce systemic toxicity or minimize the adverse effects through enhanced site-specific delivery and (iv) they release the drug in a controlled manner, thus maintaining a steady state of drug concentrations for longer periods. The controlled release mechanism represents a key aspect in the translation of nanomedicines, since reducing the frequency of administered doses would improve patient compliance and ultimately maximize the therapeutic success. This thesis describes the formulation of four anti-inflammatory drugs (BIM-I, BRP-187, TG-201 and hyperforin) into polymeric NPs. Although the drugs have shown pharmacological potential in in vitro and in vivo models, several challenges have to be overcome to develop the drugs into efficacious medicinal products. As lipophilic drugs, they exhibit a strong tendency for plasma protein binding which, consequently, reduces their overall bioavailability. Thus, to improve their pharmacokinetic profiles, nanoprecipitation and emulsion-evaporation approaches were used as bioavailability enhancement techniques to encapsulate the drugs into PLGA- and acetalated dextran-based NPs. Biodegradable nanoparticles between 30 to 210 nm were formulated, and in all cases, biological assessment of the NPs in vitro revealed that (i) NPs exhibited no cytotoxicity, (ii) they were highly uptaken into hepatocytes or macrophages and (iii) the drug-loaded NPs showed an improved bioactivity to prevent the drug targets compared to the non-formulated free drugs.


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