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Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers

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Peptide Hybrid Polymers

Part of the book series: Advances in Polymer Science ((POLYMER,volume 202))

Abstract

Recently, polypeptide hybrid polymers, particularly poly(ethylene glycol) (PEG)-polypeptide block copolymers, have been attracting significant interest for polymeric therapeutics, such as drug and gene delivery systems, utilizing their most relevant feature, that is the formation of micelles with a distinguished core-shell architecture. Of particular interest in the polypeptides is that a variety of functional groups, such as carboxyl groups and amino groups, are available as a side chain, and that they have propensities of low toxicity and biodegradability. The segregated polypeptide core of the micelle embedded in the hydrophilic palisade serves as a reservoir for a variety of drugs as well as of genes with diverse characteristics. The micelles have been developed with various functions, such as biocompatibility, stimuli- and environment-sensitivity, and targetability, aimed at their clinical use. Smart micelles have emerged as promising carriers that enhance the effect of drugs and genes with minimal side effects. In this review, recent advances in drug and gene delivery by polypeptide hybrid micelles, mostly accomplished in our group, are comprehensively described. Focus is placed on the design of PEG-polypeptide hybrid block copolymers, starting from the development of the drug-loading micelle systems to current efforts to establish a gene delivery system with a polyion complex (PIC) micelle, one of the most attractive topics in nanomedicine.

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Abbreviations

EPR effect:

enhanced permeability and retention effect

RES:

reticuloendothelial system

PEG:

poly(ethylene glycol)

NCA:

amino acid N-carboxyanhydride

PLL:

poly(l-lysine)

PAsp:

poly(α,β-aspartic acid)

PBLA:

poly(β-benzyl-l-aspartate)

PGlu:

poly(l-glutamic acid)

PEG-PAsp(DPT):

poly(ethylene glycol)-b-poly(3-[(3-aminopropyl)amino]propylaspartamide)

PEG-PAsp(DMAPA):

PEG-poly(3-dimethylamino)propyl aspartamide

PAsp(MPA):

poly[(3-morpholinopropyl) aspartamide]

PEG-PAsp(MPA)-PLL:

PEG-b-poly[(3-morpholinopropyl) aspartamide]-b-PLL

PEG-PAMA:

PEG-b-poly(2-(dimethylamino)ethyl methacrylate))

PEI:

poly(ethyleneimine)

Dox:

doxorubicin

PIC micelle:

polyion complex micelle

N/P ratio:

ratio of [amino group in polycation]/[phosphate group in polynucleic acid]

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Authors and Affiliations

  1. Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan

    Kensuke Osada & Kazunori Kataoka

  2. Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Kazunori Kataoka

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  1. Kensuke Osada
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Correspondence to Kazunori Kataoka .

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Harm-Anton Klok Helmut Schlaad

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Osada, K., Kataoka, K. Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers. In: Klok, HA., Schlaad, H. (eds) Peptide Hybrid Polymers. Advances in Polymer Science, vol 202. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_084

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