ABSTRACT
INTRODUCTION Novel therapeutic macromolecules, such as proteins or nucleic acids, are being introduced progressively into the pharmaceutical research field as a potent therapeutic promise. Biologically active macromolecules, namely, proteins, have generally low oral bioavailability and short biological half-times (1,2). The physicochemical characteristics of proteins are responsible for deficient systemic delivery, thus requiring frequent injections to maintain blood concentration within therapeutic levels. This results in oscillating protein concentration in the blood and poor patient compliance. Proteins are sensitive molecules and their three-dimensional structure can be disrupted by a number of factors such as hydrophobic environments, high shear, change in temperature or pH, and absence of water. A change in their structure could affect the therapeutic effect of proteins and also trigger adverse immune reactions. Formulation of proteins is not comparable with those of conventional low molecular weight (MW) drugs, as it is mandatory to maintain the protein’s natural structure. Also, in the case of enzymes, the catalytic activity is dependent on the free accessibility of the active center. One way to circumvent these problems is, instead of using “naked” proteins, to promote the association with delivery systems that are able to maintain protein structure and activity, change their pharmacokinetics, and deliver them to the target tissues, thus improving safety and efficacy of proteins as drugs. The most common systems to deliver proteins in vivo are nanoparticulate drug delivery systems (NPDDS), either of lipid or polymeric nature (2-4). An alternative, or complementary, strategy for the association of proteins with NPDDS as pharmaceutical nanocarriers is their administration by noninvasive routes, for example, pulmonary or transdermal delivery (5,6).
