Peptide-Based Drug Delivery Systems.

Kamila Raziyeva,Dmitriy Berillo,Arman Saparov,Zharylkasyn Zharkinbekov,Adilkhan Yeskendir

doi:10.3390/medicina57111209

Kamila Raziyeva, Dmitriy Berillo + Show 3 more

Open Access

https://doi.org/10.3390/medicina57111209

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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.

Highlights

A large number of compounds fail to progress through the various stages of preclinical and clinical studies due to a number of reasons, including but not limited to, high cytotoxicity, poor pharmacokinetic rate and inefficient site-specific targeting
The system accounted for 90% of growth inhibition in the xenograft tumor 12 days after treatment with 2.5 mg/kg dosage, which is superior to the results shown by doxorubicin (DOX) [90]
Advances in drug delivery systems (DDSs) in the scope of application of peptide conjugates has been achieved in the delivery strategies and therapeutic index of drugs

Summary

Introduction

A large number of compounds fail to progress through the various stages of preclinical and clinical studies due to a number of reasons, including but not limited to, high cytotoxicity, poor pharmacokinetic rate and inefficient site-specific targeting. Active substances at physiological conditions should be able to overcome biological obstacles such as albumin binding and aggregation, insolubility, biodegradation/metabolism, the low permeability via vascular endothelial cell layers, rapid excretion by the kidney, inefficient cellular internalization and undesirable immunogenicity [1]. These issues create a narrow therapeutic window and as a consequence, lead to dismal in vivo performance. The development of a novel drug, including all stages of clinical studies, costs about USD 2.2 billion [2]. DDSs based on synthetic stimuli responsive copolymers are widely discussed in recent reviews, including thermoresponsive [3,4], pH responsive [5,6,7] and modified natural polymers [8] that improve the stability, the effectiveness of pharmacokinetics and the tolerability of existing substances, concurrently mitigating their off-target toxicity

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