Poly(lactic acid)-poly(ethylene oxide) Block Copolymers: New Directions in Self-Assembly and Biomedical Applications

Abstract

In this review, we focus on recent developments in biomaterials of poly(lactic acid)-poly(ethylene oxide)-poly(lactic acid) (PLA-PEO-PLA) triblock copolymers. This system has been widely explored for a number of applications in controlled and sustained release of drugs and in tissue engineering devices. New insights into self-assembly of these materials have resulted in new PLA-PEOPLA solutions and gels with novel structural, mechanical, and drug release properties. Recent innovations include hydrogels with nanoscale crystalline domains, solutions and gels based on PLA stereocomplexes, and nanoparticle-copolymer assemblies. We first briefly review synthetic approaches to these materials. We then describe characterization of the solution properties, formation of micelles, drug release characteristics, and investigation of the sol-gel transition. The properties of PLA-PEO-PLA hydrogels are then discussed, including the effect of crystalline domains on the gel microstructure and efforts to tune the elastic modulus and degredation properties of gels through the addition of chemical crosslinks. In the second half of the review, we discuss the wide variety of biomedical applications currently being pursued for PLA-PEO-PLA triblock copolymer systems. Polymer-nanoparticle complexes have been investigated to facilitate the formation of metal nanoclusters used as biosensors, as well as to enhance the elastic modulus of hydrogels. Thin polymer films have also been investigated for use as tissue engineering scaffolds and as drug-eluding coatings for stents and other medical implants. Finally, we discuss future directions for biomedical applications of this system, including new strategies for improving the specificity and cell affinity of PLA-based biomaterials.

Amphiphilic multiblock copolymers of PLLA, PEO and PPO blocks: Synthesis, properties and cell affinity

“…With regard to osteoblast proliferation on PLLA 8 -b-PEO 1 -b-PPO 4 -b-PEO 1 -b-PPLA 8 films, the number of cells present on the samples was found to be even lower than those found on the PLLA 41 -b-PEO 29 -b-PLLA 41 , PLLA 11 -b-PEO 8 -b-PLLA 11 and PLLA 5 -b-PPO 1 -b-PEO 1 -b-PPO 1 -b-PLLA 5 copolymers (p < 0.05). By contrast, cell proliferation was significantly improved in the PLLA 11 -b-PEO 8 -b-PLLA 11 copolymer in comparison with PLLA 8 14 and PLLA 20 -b-(PEO 7 -ran-PPO 3 )-b-PLLA 20 (p < 0.05).…”

“…Fig. 2 shows the representative chromatograms of PLLA 11 14 and PLLA 7 -b-(PEO 2 -ran-PPO 1 )-b-PLLA 7 copolymers. A single peak is observed for each copolymer, suggesting that the PLLA homopolymer is not present.…”

“…The synthesis of diblock PLLA-b-PEO and triblock PLLAb-PEO-b-PLLA copolymers for biomedical applications has been continuously reported in prior decades, particularly in drug delivery systems, biocompatible coatings and electrospun scaffolds [7,11,12]. Block copolymers comprising PLLA and PPO blocks were studied as biodegradable copolymers by Kimura et al [13].…”

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

“…129–132 PLGA–PEG diblocks (AB) or PLGA–PEG–PLGA (ABA) copolymers are used to formulate NPs or thermogels, respectively. Due to the hydrophilicity of PEG, these chains can orient themselves toward the surface of polymeric NPs and lead to increased hydration.…”

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…In particular, the ubiquitous poly(lactic acid) (PLA) and poly(glycolic acid), and their copolymers poly(lactic-co-glycolic acid) (PLGA), have been extensively investigated in combination with poly(ethylene glycol) (PEG) [24,25]. The resulting amphiphilic block copolymers such as PLA-b-PEG and PLGA-b-PEG, selfassembled into nanoparticles, micelles or polymersomes featuring a hydrophobic PLA or PLGA core and an outer hydrophilic PEG corona [26][27][28][29][30][31]. Polyester-systems prepared from poly(-caprolactone) [32][33][34] or poly(hydroxyalkanoate)s (PHAs; vide infra), often associated with PEG, similarly form nano-sized objects.…”