Novel Structural Changes during Temperature‐Induced Self‐Assembling and Gelation of PLGA‐PEG‐PLGA Triblock Copolymer in Aqueous Solutions

Abstract

The thermoresponsive amphiphilic block copolymer poly(d,l-lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG -PLGA), which exhibits a reversible temperature-induced sol-gel transition at higher polymer concentrations in aqueous solution has attached a great deal of interest because of its potential in biomedical applications. In the present work, the length of the hydrophobic PLGA blocks is kept constant, whereas the length of the hydrophilic PEG block is altered and this variation has a pronounced impact on the phase behavior of the aqueous samples and the structure of the polymer. A short PEG block promotes gelation at a low temperature, whereas a longer PEG block shifts the gelation point to higher temperature. By using a combination of turbidity, rheology, and small angle neutron scattering (SANS) methods, the authors have revealed dramatic temperature effects. In dilute solution, the SANS experiments expose asymmetric ellipsoid structures for the copolymer with the short PEG-spacer, whereas spherical core-shell structure is observed for the polymer with long PEG-spacer. In the semidilute concentration regime, SANS measurements disclose similar profiles for the two copolymers. In a broad temperature interval, the transition from spherical core-shell micelles to cylindrical structure and packing of cylinders is observed.

Amphiphilic PLGA‐PEG‐PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid

“…Figure shows an increasing strength behavior with increasing solution concentration of samples B2‐B4. These results are supported by Khorshid et al . Having higher PEG Mw, or longer PEG chains, results in a more heterogeneous matrix, with a more open network structure (Figure ).…”

“…The higher the hydrophobicity content and the shorter the chains (especially PEG chains), the micelles aggregate more easily, forming rod‐like micelles . In contrast, sample B4 formed a gel at higher temperatures, as having higher PEG Mw, or longer PEG chains, can result in a less aggregated network structure …”

“…Is the LA/GA ratio the main variable that controls the gelation temperature? It has been hypothesized that an increment in the overall hydrophobicity of the triblock copolymers ( D,L‐ LA/GA ratio) at constant PLGA Mw, PLGA/PEG ratio, and PEG Mw is the main factor or property that yields a change in gelation temperature . Polymers with PEG Mw of 1500 Da were used for the remainder of the study as the hydrogels' gelation temperature falls within body temperature range.…”

“…At temperatures below the gelation temperature (GT), hydrogen bonding allows the copolymer to remain in solution. By the reverse thermal gelation mechanism, as temperature increases, hydrogen bonds break and hydrophobic interactions allow the copolymer to self‐assemble into flower‐shaped micelles, aggregating and bridging . The PEG chain forms loops on the surface, while the PLGA chains form the core of the micelles .…”

“…The PEG chain forms loops on the surface, while the PLGA chains form the core of the micelles . The molecular structure of a medically relevant hydrogel is dependent on the different parameters of the triblock copolymer: hydrophilic/hydrophobic ratio (PLGA/PEG ratio), PLGA monomer ratio ( D,L‐ LA/GA ratio), PLGA molecular weight (PLGA Mw), PEG molecular weight (PEG Mw), triblock copolymer molecular weight (Mw), polydispersity index (PDI), and polymer solution concentration . By controlling such parameters, a desired hydrogel with a wide range of medical applications can be achieved …”