(182f) Polymeric Drug Delivery Systems for Small Hydrophilic Molecules

The clinical application of many drugs can be limited by rapid clearance from the systemic circulation or a local site of administration necessitating frequent dosing. This is particularly true of small molecule drugs of biopharmaceutical classification types I and III (hydrophilic or amphiphilic drugs). The pharmacokinetics and therefore the therapeutic effect of some such compounds can be improved by encapsulating them in delivery systems which allow sustained release, prolonging the duration of effect. However, the high-water solubility, very hydrophilic nature, and low molecular weight make it difficult to encapsulate small hydrophilic molecules in many conventional drug carriers, such as poly(lactic-co-glycolic acid) (PLGA) particles and hydrogels. Here, tetrodotoxin (TTX), a naturally occurring neurotoxin, was selected as a small hydrophilic molecule model. We will introduce some novel polymeric drug delivery systems that have been validated to efficiently encapsulate TTX and achieve TTX controlled release. Applications of these formulations in chronic pain management will be presented. The principles of polymer design and the mechanisms underlying the material performances will be discussed.