Figure 1. The change in volume swelling ratio of PAA/PAAm IPN nanospheres suspended in water as a function of temperature. Error bars represent one standard deviation, n=3.
Figure 2. Scanning electron microscopy image of dried and gold sputter coated PAA/PAAm IPN nanospheres. Scale bar (green) represents 300nm.
The small size and unique properties of nanoparticles make them an ideal in vivo delivery system for the treatment of a wide variety of diseases including cancer, diabetes, multiple scleroses, and many others. These systems have the ability to safely localize and release therapeutic levels of potent drugs, such as chemotherapy agents, thereby lowering systemic doses, reducing side effects, achieving higher patient compliance and improved quality of life. Interpenetrating Polymer Network (IPN) nanoparticles are unique in that they can exhibit a positive sigmoidal swelling transition with temperature instead of the negative or linear temperature response exhibited by most conventional random copolymers. This distinctive swelling behavior, which can act as an on/off mechanism for controlled drug release, makes IPNs an ideal candidate for therapeutic systems.
In this paper we explored temperature-responsive IPN nanoparticles composed of poly(acrylic acid) (PAA) and polyacrylamide (PAAm) in various compositions. These polymers were chosen based on their ability to create secondary hydrogen bonding complexes, which allow them to remain in a collapsed state at temperatures below their upper critical solution temperatures (UCST), and a swollen state above. Overall, this property gives the IPN a sharp swelling transition over a narrow temperature range (Figure 1). This is advantageous because drug release can be controlled by changing the temperature locally within the IPN by only a few degrees. In these studies, the PAA/PAAm latex IPN nanospheres were prepared by sequential water in oil inverse emulsion polymerization. In this process, the second monomer acrylic acid was polymerized with additional crosslinker and initiator inside the original seed latex of polyacrylamide.
The results of this paper clearly indicate that IPN nanospheres were successfully synthesized. Swelling studies using dynamic light scattering (DLS) showed a sigmoidal transition at 40+/-5˚C, which is characteristic of IPN systems (Figure 1). The morphology of the particles was characterized using scanning electron microscopy (SEM). The particles appeared spherical and fairly monodisperse in the SEM (Figure 2), and DLS results showed an average particle diameter of between 300 and 400 nm.
This work was supported by grants from the National Institutes of Health (EB 000246) and the National Science Foundation (DGE-0333080).