The dominant role of polymer erosion in paclitaxel release from folate-modified poly(ether-anhydride) nanocarrier

摘要

This study designed a photo-crosslinkable poly(ether-anhydride) nanocarrier with folate modification to achieve both biodegradability and active targeting. The nanocarrier consists of a hydrophobic polymer core and a shell of folate and hydrophilic poly(ethylene glycol). Nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to verify the synthesis and relevant intermediate products. The nanocarrier was characterized in terms of morphology and diameter using transmission electron microscopy and dynamic light scattering. The results showed that the size of spherical nanocarriers located within 200-400 nm. The cellular uptake profile of nanocarriers in HeLa cells was examined using fluorescence microscope with the help of a fluorescent molecule and the folate-modified nanocarrier exhibited an enhanced uptake compared to that without modification. The nanocarrier degradation at physiological temperature was investigated gravimetrically and the in vitro release of model drug, paclitaxel (PTX) was examined via the dialysis method. The erosion rate of poly(ether-anhydride) network was controlled by the crosslinking density and the hydrolytic susceptibility; the folate modification slightly slowed the degradation process. The time scale of PTX release perfectly matched with that of nanocarrier erosion; after 6 h more than 50% weight loss of nanocarrier was observed and meanwhile the drug release profile got plateaued, indicating the dominant role of polymer erosion in the release of the active agent from the nanocarriers.