Dual- or multiresponsive nanocarrier are exciting developments in the field of stimuli- sensitive drug delivery. These systems in general can orthogonally respond to two or more stimuli. The combination involves pH and ionic strength, pH and thermoresponsiveness, or pH and carbohydrates. These dual-responsive systems are developed by a combination of two monomers having responsiveness to different stimuli. Of the multiresponsive systems, pH and temperature-responsive NFs are the most studied. One potential advantage ofdual-responsive systems is the fact that one stimulus can be utilized to load the carrier, whereas a second one can be used to trigger the release. However, the design ofmultiresponsive NF remains a challenge because these systems are composed of several blocks, each with a different stimulus [19,46].
Challenges in Stimuli-Responsive Drug Delivery Applications of Nanofibers
Rapid progress has been made in the development of stimuli-responsive polymeric NFs in biomedical applications. However, a majority of these systems have not made it past the preclinical stages due to several limitations and challenges. There are several limitations of NF stimuli-responsive systems that need to be solved before these systems can proceed to clinical trial. The complex formulation steps, scaling up of the synthesis, and use of multiple components need to be simplified. External stimuli sources need improvement to achieve better tissue penetration without causing any damage to other nonspecific tissues. Although the NFs have been successfully fabricated, these systems have not been thoroughly investigated relative to stimuli-responsive potential. Moreover, potential toxicity of polymers involved in the stimuli-sensitive therapeutics including the slow response of NFs needs improvement and further evaluation. In addition to the above-mentioned challenges, the degradation product of any stimuli-sensitive system must be biocompatible and safe before it can be translated. These barriers impede the optimal performance ofstimuli-responsive delivery systems. Although there are many challenges, a number of opportunities in the development of smart polymeric drug delivery systems are being contemplated.