A stimuli-responsive nanocarrier provides a smart system for various therapeutic applications [15]. Generally, stimuli-responsive systems are able to enhance/trigger the release of therapeutic drugs in response to triggering signals (intrinsic or extrinsic). The intrinsic signals include pH, temperature, enzymes, and oxidative stress, whereas external stimuli constitute magnetic field, light, and heat [15,16]. These stimuli are applied as a triggering element in nanocarrier drug delivery systems [17,18]. The release of therapeutic molecules is controlled in a spatial and temporal manner [19]. Here, we have briefly summarized different stimuli that have been applied for triggering the drug release from NFs (Fig. 9.2). The delivery systems, which release active molecules in response to specific stimuli at the target site, are shown in Table 9.2 and Fig. 9.3.

pH-Responsive Systems

Variations in pH have been exploited to trigger drug release from delivery systems [18]. The use of polymers with ionizable groups (carboxylic, sulfonate, and amino) undergo conformational and/or solubility changes in response to environmental pH variation to release therapeutic molecules. pH-responsive systems are suitable for thermolabile drugs. Several NF systems have been developed with pH-sensitive polymers such as poly (e-caprolactone) (PCL), poly (lactic acid-co-glycolic acid) (PLGA), and silk. Polymers with ionizable groups are classified into two types: weak polyacids and weak polybases. Poly (acrylic acid) and poly (methacrylic acid) are commonly used as pH- responsive polyacids, whereas poly(N,N-dimethylamino ethylmethacrylate) and poly(N,N-diethylaminoethylmethacrylate) are pH-responsive polymeric bases [20,34,35].

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