PEGylation and Cell-Penetrating Peptides: Glimpse into the Past and Prospects in the Future

Abstract

Several drug molecules have shown low bioavailability and pharmacokinetic profile due to metabolism by enzymes, excretion by the renal system, or due to other physiochemical properties of drug molecules. These problems have resulted in the loss of efficacy and the gain of side effects associated with drug molecules. PEGylation is one of the strategies to overcome these pharmacokinetic issues and has been successful in the clinic. Cell-penetrating Peptides (CPPs) help to deliver molecules across biological membranes and could be used to deliver cargo selectively to the intracellular site or to the drug target. Hence CPPs could be used to improve the efficacy and selectivity of the drug. However, due to the peptidic nature of CPPs, they have a low pharmacokinetic profile. Using PEGylation and CPPs together as a component of a drug delivery system, the and efficacy of drug molecules could be improved. The other important pharmacokinetic properties such as short half-life, solubility, stability, absorption, metabolism, and elimination could be also improved. Here in this review, we summarized PEGylated CPPs or PEGylation based formulations for CPPs used in a drug delivery system for several biomedical applications until August 2019.

Keywords: Bioavailability; Cell-penetrating peptides; Cellular uptake; Drug delivery system; PEGylation; Polyethylene glycol; Stability; Toxicity..