Peptide-Based Drug Delivery Systems

Abstract

Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide–drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed.

Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin

“… 295 Peptide-based NPs are easy to synthesize, customizable, have better biosafety, and can recognize bioreceptors on the surface of cancer cells for targeting, but they also suffer from unstable physicochemical properties, susceptible to oxidative hydrolysis, prone to agglomeration, short half-life and does not easily cross cell membranes. 296 Similar to peptides, polysaccharide-based NPs have excellent biocompatibility and degradability, and they are also readily available and easily modified, however, when they are used in practice, they are also found to have problems of easy swelling and premature disintegration. 297 Cell membrane-based NPs have attracted much attention because of their cell-specific targeting, long circulating half-life and immune escape function, but it is difficult to ensure that the cell membrane can be completely coated on the drug surface when they are prepared, and it is also difficult to control the inner and outer surfaces of the cell membrane.…”

Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery

“…The cytotoxicity effects of PDCs depend on several factors, including biostability, the rate of penetration, efficiency of the drug release, and drug toxicity. The ability of the peptide–drug conjugates to remain stable and to specifically enter the target cells is an important factor in the delivery of highly toxic drugs [ 68 , 69 ]. Our PDCs showed half-lives of 6–7 h, which might be significantly enhanced by further manipulation, such as PEGylation [ 70 ], or conjugation to gold nanoparticles [ 25 ].…”

Hunting for Novel Routes in Anticancer Drug Discovery: Peptides against Sam-Sam Interactions

“…CPPs can be grouped considering their physicochemical properties (i.e., cationic, amphipathic and hydrophobic CPPs), their origins (i.e., protein-derived, chimeric and synthetic CPPs), or other clinically relevant features (i.e., cell-specific and non-cell-specific CPPs) [ 35 ]. CPPs are able to employ diverse mechanisms to overcome cell membranes [ 5 , 34 , 35 , 36 ]. One of them relies on direct penetration, which is energy-independent, mainly characterizes cationic CPPs, and depends on the destabilization of the cell membrane [ 5 , 35 , 36 ].…”

“…CPPs are able to employ diverse mechanisms to overcome cell membranes [ 5 , 34 , 35 , 36 ]. One of them relies on direct penetration, which is energy-independent, mainly characterizes cationic CPPs, and depends on the destabilization of the cell membrane [ 5 , 35 , 36 ]. Membrane perturbation and direct entry can be related to the peptide-induced formation of inverted micelles in the case of amphipathic peptides or the development of transmembrane potential-modulated water pores; in addition, sphingomyelin and ceramides can also be involved into the direct penetration mechanism by modulating membrane fluidity [ 34 ].…”

“…Membrane perturbation and direct entry can be related to the peptide-induced formation of inverted micelles in the case of amphipathic peptides or the development of transmembrane potential-modulated water pores; in addition, sphingomyelin and ceramides can also be involved into the direct penetration mechanism by modulating membrane fluidity [ 34 ]. Moreover, CPP-mediated cell penetration may exploit different energy-dependent endocytic routes including clathrin- and caveolin-mediated endocytosis as well as macropinocytosis [ 5 , 34 , 35 , 36 ]. Endocytic internalization is characterized by the formation of vesicles (named endosomes) in which the peptides are inserted to overcome the cell barrier [ 34 ].…”