As an example, negatively-charged liposomes were preferred to their positively-charged counterparts to prevent interactions with negatively charged GelMA, which could insert in the bilayer and destabilize the liposome. Similarly, the internal structure of a double-network hydrogel made of Gel and Dex-CHO was rapidly destabilized by amino-functionalized iron oxide NPs becoming protonated in acidic medium and diminishing their ability to serve as crosslinking centers. A charge switch can also be exploited to achieve a controlled release in specific media. An ALG-based hydrogel, shrunk at low pH values, turned into a swollen material that lost the ability to retain entrapped liposomes and repelled them, due to their shared negative charge, when the pH of the medium increased (Figure ). Similar behavior was observed in a hybrid system made of PCL-PEI NPs and CS. The electrostatic repulsion, triggered in this case at low pH values by protonation of amines, led to rapid NP release which reached over 90% within 12 h. The interaction between dispersed nano-objects and drug molecules within the gel matrix is also important for promoting drug retention and slowing down the release. The large and charged surface of Lap NPs facilitated effective adsorption of β-galactosidase (β-gal) in a PLGA-b-PEG-b-PLGA triblock copolymer hydrogel. This interaction guaranteed a gradual release, with over 50% of the enzyme still retained after 19 days (Figure ). Figure . (a) SEM photographs of liposome/ALG hybrid hydrogel at pH 1.2 and 6.4 with a schematic representation of the pH responsive behavior leading to the release of the loaded liposomes at higher pH values. Adapted with permission. Copyright 2022 Elsevier. permission. Copyright 2021 American Chemical Society.