Formulation of hydrogel and nanoparticle hydrogel encapsulated with L-theanine: comparative release analysis and antioxidant activity

Over the past decade, hydrogels have garnered significant interest in drug delivery, wound healing, and tissue engineering because of their high water content, biocompatibility, and tunable physicochemical properties. A bioactive amino acid, L-theanine, is known for its neuroprotective, antioxidant, and anticancer properties. The objective of this study is to design and evaluate a composite hydrogel system to encapsulate and release L-theanine over time. Three different types of hydrogels (PVP-G HG, PVP-G@Th HG, and PVP-G@Th-NP HG) were prepared via a hybrid crosslinking approach involving glutaraldehyde chemical gelation and freeze-thaw physical texturing, and characterized by SEM, FTIR, and PXRD, confirming successful formation of the hydrogel and drug encapsulation. The gel fraction of the hydrogel was evaluated by measuring the amount of crosslinking inside the hydrogel as 74.576% ± 1.03%. From the formulations, PVP-G@Th HG exhibited higher swelling capacity in water (1033.53% ± 9.25%). Weight loss was seen during the in vitro degradation period of 7 days, where PVP-G HG, PVP-G@Th HG, and PVP-G@Th-NP HG were degraded by 34.32% ± 0.58%, 40.71% ± 0.76%, and 45.32% ± 0.71%, respectively. The drug release studies for 48 h showed sustained L-theanine release from PVP-G@Th HG (69.48%) and PVP-G@Th-NP HG (42.23%), with the Higuchi model (R 2 = 0.996) and the Korsmeyer-Peppas model (R 2 = 0.973), respectively. The antioxidant activity evaluated by DPPH showed a good radical scavenging effect in which the highest activity was observed for PVP-G@Th HG (80.71% ± 0.92%) at 450 min, followed by PVP-G@Th-NP HG (75.83% ± 1.23%). The nanoparticle (NP)-loaded L-theanine (Th) hydrogel (HG) (PVP-G@Th-NP HG) exhibited a slower and more controlled release profile than the directly loaded hydrogel (PVP-G@Th HG), reflecting more regulated release kinetics rather than a greater extent of release. This formulation may therefore offer a more sustained delivery profile suitable for further evaluation in controlled drug-delivery applications.