Double hydrophilic block copolymers self-assemblies in biomedical applications

Abstract

Double-hydrophilic block copolymers (DHBCs), consisting of at least two different watersoluble blocks, are an alternative to the classical amphiphilic block copolymers and have gained increasing attention in the field of biomedical applications. Although the chemical nature of the two blocks can be diverse, most classical DHBCs consist of a bioeliminable non-ionic block to promote solubilization in water, like poly(ethylene glycol), and a second block that is more generally a pH-responsive block capable of interacting with another ionic polymer or substrate. This second block is generally non-degradable and the presence of side chain functional groups raises the question of its fate and toxicity, which is a limitation in the frame of biomedical applications. In this review, following a first part dedicated to recent examples of nondegradable DHBCs, we focus on the DHBCs that combine a biocompatible and bioeliminable non-ionic block with a degradable functional block including polysaccharides, polypeptides, polyesters and other miscellaneous polymers. Their use to design efficient drug delivery systems for various biomedical applications through stimuli-dependent self-assembly is discussed.

Antioxidants: Classification, Natural Sources, Activity/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles

“…Interesting nano-formulas are also doubly hydrophilic self-assembling block copolymers (DHBC), which in recent years have aroused more and more interest not only for the production of nanoparticles, but also as controlled drug distribution systems. A valuable review on DHBC was published in 2020 by Jundi et al [ 459 ].…”

Block copolymer solution self‐assembly: Recent advances, emerging trends, and applications

“…All the self‐assembly processes discussed so far are mainly driven by hydrophobic interactions. An alternative way to promote self‐organization is by exploiting electrostatic interactions, especially when discussing BCPs that bear charged blocks 113–115 . These double hydrophilic block copolymers (DHBCs) are capable of interacting electrostatically with a wide range of oppositely charged species, for instance linear homo‐ and block‐polyelectrolytes, biopolymers, DNA and RNA, proteins, surfactants, metallic complexes, nanoparticles, etc.…”

“…One last important aspect influencing morphology is the composition of the interacting BCPs and especially the block lengths ratios, in an analogy to classical micelles, that is, relatively long neutral soluble blocks produce spherical “star‐like” micelles, but shorter corona‐forming blocks usually result in “worm‐like” micelles or vesicles. Some typical examples of polymers used for such formulations include anionic PAA and poly(methacrylic acid) (PMA), or cationic poly(2‐dimethylamino ethyl methacrylate) (PDMAEMA), poly(ethyleneimine) (PEI), along with biocompatible poly( L ‐lysine) (PLL), poly(aspartic acid) (PAsp) and poly( L ‐glutamic acid) (PGlu), while for the corona forming blocks PEO/PEG is the most widespread choice 113,114 …”

“…Ever since the pioneer work of Harada and Kataoka in 1995, 116 PIC micelles have maintained their strong scientific allure primarily because of their potential biotechnological applications, especially relevant to nanomedicine for controlled delivery and release of bioactive and therapeutic molecules, including biomacromolecules. For such systems it is possible to choose DHBCs with charged not only biocompatible but also biodegradable blocks, e.g., polysaccharides, polypeptides, and polyesters, as the interacting segments 114 . Upon complexation of these BCPs with low or high MW active pharmaceutical ingredients (APIs) of relevant importance (i.e., drugs, proteins, peptides, genes), PIC micelles are formed that are able to undergo stimuli‐responsive (typically pH or ionic strength related) destabilization/degradation, thus releasing their pharmaceutical payload, as schematically depicted in Figure 9.…”

“…Formation of polyion complex (PIC) micelles based on degradable double hydrophilic block copolymers (DHBCs) and high or low MW active pharmaceutical ingredients (APIs), and their subsequent stimuli‐responsive destabilization and release. Reproduced with permission from Reference 114 copyright (2020) Elsevier…”