Mixing a Sol and a Precipitate of Block Copolymers with Different Block Ratios Leads to an Injectable Hydrogel

Abstract

A facile method to obtain a thermoreversible physical hydrogel was found by simply mixing an aqueous sol of a block copolymer with a precipitate of a similar copolymer but with a different block ratio. Two ABA-type triblock copolymers poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) were synthesized. One sample in water was a sol in a broad temperature region, while the other in water was just a precipitate. The mixture of these two samples with a certain mix ratio underwent, however, a sol-to-gel-to-precipitate transition upon an increase of temperature. A dramatic tuning of the sol-gel transition temperature was conveniently achieved by merely varying mix ratio, even in the case of a similar molecular weight. Our study indicates that the balance of hydrophobicity and hydrophilicity within this sort of amphiphilic copolymers is critical to the inverse thermal gelation in water resulting from aggregation of micelles. The availability of encapsulation and sustained release of lysozyme, a model protein by the thermogelling systems was confirmed. This "mix" method provides a very convenient approach to design injectable thermogelling biomaterials with a broad adjustable window, and the novel copolymer mixture platform is potentially used in drug delivery and other biomedical applications.

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

“…Then, lysozyme, chosen as model protein, was used to examine whether or not this thermogelling mixture systems could encapsulate and deliver biological substances such as proteins in a biologically active form, for long duration demonstrating that the release rate could also be adjusted by the mix ratios of copolymer mixtures, and an almost zero-order sustained release of lysozymes was achieved up to 50 days. Thus the obtained results outlined that the -mix‖ method provides a very convenient approach to design injectable thermogelling biomaterials with a broad adjustable window, and the novel copolymer mixture platform can be potentially used in drug delivery and other biomedical applications [85].…”

Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

“…This behavior might be attributed to an excess of hydrophobic HEMAPCL which led to a high density of crosslink sites on each copolymer chain and a high tendency of agglomeration during the hydrophobic association, thus preventing effective gel formation. 21 Comparing the gelation behavior of copolymer with different concentrations, gelation occurred faster for those with higher concentration. However, there was no significant difference in the gelation time among the hydrogels with different monomer composition.…”

“…So far, both natural macromolecules like collagen, 15 chitosan, 16 gelatin, 17 alginate 18 and hyaluronic acid 19 and synthetic polymers such as poly(N-isopropylacrylamide) (PNIPAAm), 20 poly(ethylene glycol)/poly(lactic acid-co-glycolic acid) (PEG/PLGA) copolymers, 21 poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers, 22 and Pluronic ® (PEO-PPO-PEO; BASF Corporation, Ludwigshafen, Germany), 23 or their combinations 24 have been utilized to produce injectable hydrogels. As one of the most widely used injectable hydrogels, PNIPAAm is a thermosensitive intelligent material which undergoes a reversible sol-gel transition around 32°C in an aqueous condition, converting from flowable solution to hydrogel when heated above its lower critical solution temperature (LCST).…”

Injectable hydrogels

“…135,136 Such gels are often referred to as self-assembling or nanoassembling gels. Self-assembling hydrogels are shear thinning that allows for injectability after subjecting the material to stress and then gels on subsequent recovery of its mechanical properties in situ.…”