Thermosensitive hydrogel-containing polymersomes for controlled drug delivery

PNIPAAm-containing polymersomes (N/Ps) were prepared by injecting a solution of poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-PDLLA) and poly(N-isopropylacrylamide) (PNIPAAm) in THF into water to incorporate PNIPAAm into polymersomes (Ps). At 37 °C, hydrogel-containing Ps (Hs, hydrosomes) with an average diameter of 127 nm as measured with dynamic light scattering (DLS) were obtained which may be used as potential novel carriers for anticancer drugs and proteins. Dual-labeled N/Ps (FITC-N/RB-Ps) were prepared analogously using rhodamine B tagged mPEG-PDLLA (mPEG-PDLLA-RB) and fluorescein isothiocyanate labeled PNIPAAm (FITC-N). The co-localization of RB labeled Ps (RB-Ps) and FITC-N in RB-Ps was shown by dual fluorescence CLSM. Fluorescence correlation spectroscopy (FCS) and fluorescence anisotropy (FA) measurements with these systems gave further evidence for the colocalization of PNIPAAm and Ps. Micron-sized giant Ps with a diameter of 5–10 μm containing FITC-N were prepared using CHCl3 as the organic phase. The presence of FITC-N in these giant Ps as well as the phase separation of the internal FITC-N solution above the lower critical solution temperature (LCST) was also shown by CLSM. The release of fluorescein isothiocyanate tagged dextran (FD, FITC-dextran, Mw 4000 g/mol) from Hs revealed that in the presence of the hydrogel at 37 °C a more sustained release of FD (up to 30 days) with a low initial burst effect was obtained as compared to the release from bare Ps.

A PNIPAAm solution introduced into the core of polymersomes phase-separates and partially turns into a gel above the LCST, which decreases the release rate of the model compound dextran (4 K).Figure optionsDownload as PowerPoint slide