Biodegradable Polymersomes from Poly(2-hydroxyethyl aspartamide) Grafted with Lactic Acid Oligomers in Aqueous Solution

Abstract

Amphiphilic molecules self-assemble into various structures such as spherical and cylindrical micelles, lamellae, and vesicles in aqueous media, organic solvent, or a mixture of both of these items. [1][2][3] Those self-assemblies have been extensively studied for the past decade due to their unique characteristics and the variety of applications in many areas including the biomedical field. In particular, the vesicular aggregates made of block copolymers, known as polymersomes, 4 have been paid a great deal of recent attention with their high potential use as cellmimicking systems, 5 biosensors, 6 containers or reactors, 7 and vehicles for delivery of bioactive agent. 5,8,9 But until now, studies of polymer vesicles were focused on di-or multiblock copolymers. 5,[10][11][12][13] Although graft copolymers could easily have diverse functionalities by conjugation of functional moieties or drugs onto the polymer backbone, in most cases, spherical micelles were formed as shown in our previous works. [14][15][16] Here, we report the synthesis of novel amphiphilic graft copolymer, poly(2-hydroxyethyl aspartamide) grafted with lactic acid oligomers (PHEA-g-LA), and the structural transition of the self-aggregates as a function of DS (degree of substitution, mole percent of grafted LA segments) which is related to hydrophobic/hydrophilic block ratio. To our best knowledge, we first report the formation of the polymer vesicles from comblike traditional graft copolymers. Besides, the use of aqueous media and the biocompatibility and biodegradability of copolymer material of our system would be essential for later application as delivery carriers.All synthetic routes and the molecular structure of PHEAg-LA are shown in Scheme 1. The precursor polymer, poly-(succinimide) (PSI), was presynthesized by the acid-catalyzed polycondensation of L-aspartic acid using phosphoric acid as the catalyst as previously reported. 16 PHEA containing amine group was prepared by aminolysis of PSI with 0.9 equiv ethanolamine and excess amount of ethylenediamine, respectively. Lactic acid oligomers (LAs) were synthesized by ringopening polymerization of L-lactide using 1-octanol as initiator, and stannous octate as catalyst and purified with diethyl ether. 17 The number-average molecular weight and PDI of LA measured by MALDI-TOF mass spectroscopy were 2412 and 1.02, respectively. The hydroxyl group at the chain terminus of LAs was activated with coupling agent N,N-carbonyldiimidazole (CDI) (LA-CDI), for the grafting reaction. LAs were grafted to the backbone through the formation of carbamate linkage by reaction of amine group in the backbone polymer and purified LA-CDI. In this step, we can control the DS of copolymer

Polymer Vesicles Containing Small Vesicles within Interior Aqueous Compartments and pH‐Responsive Transmembrane Channels

“…When the pH value is increased to 6.5, the channels become permeable upon abrupt disruption of hydrogen bonds and hydrophobic association of un-ionized AAc units by the presence of a critical amount of ionized AAc units within the channels. The tendency toward forming vesicles is largely influenced by the distribution of DSA grafts within the copolymers, the hydrophilic/hydrophobic balance, and the stiffness of copolymers, [2,13] which, in turn, is closely related to the conjugation approach and the extent of DSA and ionization degree of AAc units along the polymer backbones. As the copolymers were prepared by postmodification of polymeric precursor, it is reasonable to postulate that distribution of DSA within the copolymers occurred in a multiblock manner with pertinent main-chain spacing from the AAc units (for decoupling the motion of the polymer main chain and the lipid grafts), [14] thereby promoting the intermolecular association [15] and formation of lipid bilayers and AAc-rich channels within vesicle membranes.…”

Novel polymersomes based on amphiphilic graft polyphosphazenes and their encapsulation of water-soluble anti-cancer drug

“…Most of the investigations about polymersomes have been focused on block copolymers. Polymers with other kinds of architectures were not studied until very recently Lee et al [3] first proclaimed their research on polymersome formation by comb-like traditional graft copolymers. However, there are still lacks of research work about drug delivery of polymersomes based on graft copolymers.…”

A direct surface modification of iron oxide nanoparticles with various poly(amino acid)s for use as magnetic resonance probes

“…1B). The peak at 5.3 ppm was assigned to the methane protons of the succinimide unit, respectively, while peaks at 0.8, 1.2 and 1.3 ppm (marked with symbols) were assigned to the octadecyl chain [29][30][31][32][33]. The grafted mole percentage, defined as the degree of substitution (DS), of C 18 , was 12.43.…”

“…However, PSI-g-C 18 cannot be directly used to stabilize hydrophobic nanoparticles in water because the PSI backbones are also not soluble in water [29][30][31][32]. PSI can be easily aminolyzed with nucleophilic compounds to form various poly(amino acid)s known to be biodegradable, biocompatible, and water-soluble (Scheme 2).…”

“…Biocompatible and biodegradable poly(a-amino acid)s and their derivatives synthesized from poly(succinimide) can be excellent alternative materials and are already widely investigated as drug delivery carriers [29][30][31][32][33][34] because of their biodegradability by proteloytic enzymes [35,36]. Poly(a-amino acid)s have many attractive properties such as absence of toxicity, antigenicity, and immunogenicity [37].…”