Abstract
Poly-N-isopropyl acrylamide (PNIPAM) nanogels have been modified with different acrylic acid (AAc) contents for the efficient control of lower critical solution temperature (LCST). In this study, PNIPAM-co-AAc nanogels nanogels showed two volume phase transitions in comparison with PNIPAM. The transition temperature of PNIPAM nanogels was increased with AAc contents. The controlled drug release performance of PNIPAM-co-AAc nanogels loaded with β-lapachone was attributed to the AAc content ratio and was efficiently triggered in response to temperature and pH. Moreover, a colorimetric cell proliferation assay and direct fluorescence-based live/dead staining were used to confirm the concurrence on drug release profiles. Finally, PNIPAM-co-AAc20 showed a relatively low level of drug release in the range of acidic to neutral pH at body temperature, while maximizing drug release at basic pH. Therefore, we demonstrated that the PNIPAM-based nanogel with the temperature- and pH-responsive features could be a promising nanocarrier for potential intestine-specific drug delivery.
Highlights
Stimuli-responsive nanocarriers have generally been developed as drug delivery systems for therapy, imaging, and diagnostics [1, 2]
Aqueous solutions of Poly-N-isopropyl acrylamide (PNIPAM)-co-AAc5 persisted as a sol phase at room temperature, the nanogel transitioned into the gel phase upon heating, resulting in the solution becoming turbid above the lower critical solution temperature (LCST) (Fig. 1c)
The zeta potentials of the PNIPAM, PNIPAM-co-AAc5, PNIPAM-co-AAc10, and PNIPAM-co-AAc20 decreased to − 13.56 mV, − 16.61 mV, − 21.87 mV, and − 23.62 mV due to the increased amount of surface carboxyl groups provided by the acrylic acid (AAc) contents (Fig. 1d)
Summary
Stimuli-responsive nanocarriers have generally been developed as drug delivery systems for therapy, imaging, and diagnostics [1, 2]. Various stimuli including pH, temperature, biomolecules, redox, magnetic field, and ultraviolet light have been used to induce sustained or controlled drug release via an internal or external activation [3–6] Among these stimuli, pH and temperature are the most well-known modalities in drug delivery and release systems. Poly-N-isopropyl acrylamide (PNIPAM) is a representative temperature-responsive polymer that has been utilized in drug reservoirs and release systems This thermo-sensitive polymer has the ability to alter its phase behavior, exhibiting a swollen state because of hydrogen bonding between water and amide functional groups at the lower critical solution temperature (LCST) and exhibiting shrinkage of the polymer network via PNIPAM-mediated drug delivery systems have been developed for various applications in biomedical fields.
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