Immediate-sustained lactate release using alginate hydrogel assembled to proteinase K/polymer electrospun fibers

Enzymatic Degradation of Polylactic Acid Fibers Supported on a Hydrogel for Sustained Release of Lactate

“…The smooth cylindrical PLA fibers (Figure b1), which exhibit an average diameter (ø) of 598 ± 194 nm, were significantly affected by plasma treatment, producing grooves at the surface (ø = 614 ± 152 nm; Figure b2); meanwhile, the incorporation of proteinase K produced nanopores at the surface of the electrospun fibers, as well as an increase in diameter (ø = 784 ± 149 nm; Figure b3). Thus, plasma-treated K(26)/PLA fibers bring together the effects of both the plasma and the enzyme (ø = 917 ± 117 nm; Figure b4) . While the grooves were attributed to the oxidation and rupture of PLA chains during plasma treatment, , the superficial nanopores were ascribed to the phase separation caused in the electrospinning feeding solution by the water adsorbed by the hydrophilic enzyme …”

“…Also, lactate was released by degrading a subcutaneous implant of poly- d , l -lactide- co -glycolide (PLGA) as well as PLGA microspheres . Following similar degradation principles, lactate was delivered from films and microfibers made of polylactic acid (PLA) with a high L enantiomer content. , Pineda et al followed a different approach to develop a therapeutic strategy against malignant brain glioma, which was based on the intracellular release of lactate loaded on silica nanoparticles.…”

“…Development of bioplatforms for drug delivery based on the combination of micro/nanofibers and hydrogels with both components playing an active role in the release is becoming a topic of growing interest by different reasons. − Due to their capability to absorb large amounts of water and their biomechanical similarity to an extracellular matrix (ECM), hydrogels have been chosen to produce tissue engineering scaffolds or as injectable delivery systems. − Furthermore, the open structure of hydrogels, in combination with the hydrophilic nature of the constituent polymer, facilitate the diffusion and fast release (from a few hours to a few days) of previously loaded hydrophilic drugs, ,, including lactate . In contrast, fibers made of biodegradable hydrophobic polymers present a compact structure and exceptionally high surface area, which not only favors cell cardiac performance but also allows a sustained drug release when they act as carriers, regardless of the hydrophilic or hydrophobic nature of the drug. − In fact, the release of drugs from such types of fibers is usually controlled by the degradation of the polymer.…”

“…In contrast, fibers made of biodegradable hydrophobic polymers present a compact structure and exceptionally high surface area, which not only favors cell cardiac performance but also allows a sustained drug release when they act as carriers, regardless of the hydrophilic or hydrophobic nature of the drug. − In fact, the release of drugs from such types of fibers is usually controlled by the degradation of the polymer. In the case of biodegradable PLA, it was shown that fibers can be used for a sustained release of lactate. , …”

“…Indeed, the degradation of hydrophobic and crystalline PLA micro/nanofibers is too slow, even in a physiological environment, to match the regeneration rate of cardiac tissues. Controlled plasma treatments have been used to transform hydrophobic PLA into hydrophilic, ,, which should increase the degradation rate. However, this strategy alone might not be effective enough to achieve a significant amount of lactate, as a degradation byproduct, in just a few weeks.…”