Liposomal pH-sensitive nanomedicines in preclinical development

Abstract

In order to increase the therapeutic efficacy of a drug or to reduce its toxicity, biodistributionand intracellular traffic have to be changed, since the sole modification of its pharmacokinetics is insufficient. Nanomedicines (nano-objects loaded with small drugsor macromolecules) are powerful tools developed in the framework of the applicationof nanotechnology to medicine that, functioning as nano-drug delivery systems, are capable of modifying the pathway followed by molecules. Pharmacokinetics, biodistribution, and intracellular traffic of loaded molecules no longer depend on their chemicalstructures but on the size, shape, and chemical structure of the nano-object. Liposomes, for instance, are the best known example of nano-objects, recently clasified as nanoparticules (with their three dimensions in the nanoscale (<200?300 nm). Different from conventional drug delivery systems, and depending on the biodegradability of the nanoobject,nanomedicines can cross anatomical and phenomenological barriers. They can be administered by parenteral, transcutaneous, or mucosal vias, but changes in biodistribution can only be achieved upon parenteral administration. An exclusive feature of nanomedicines is their uptake by phagocytic or pynocitic mechanismsupon cell recognition. The structure of the nanomedicine is responsible for its own recognitionby a given mechanism of cellular uptake. Each uptake mechanism leads to well-defined intracellular traffic mediated by vesicles, which ends up in different cellular compartments. The control of biodistribution and kinetics of selective delivery into cell compartmentsis the key to generate more efficient and less toxic therapeutic effects. Tissue and cell targeting,as well as controlled intracellular traffic, depend on the size and structure of thenano-object, which must be administered parenterally.