Polymeric membranes with selective permeability : shielding of an antioxidant enzyme

In this work we designed an antioxidant nanoreactor based on the encapsulation of
CuZnSOD in amphiphilic copolymer nanovesicles. The nanovesicles are formed by
self-assembly of amphiphilic copolymer poly-(2-methyloxazoline)-poly-
(dimethylsiloxane)-poly-(2-methyloxazoline) (PMOXA-PDMS-PMOXA). We chose
this polymer due to its advantages over conventional systems, i.e. liposomes.
Polymer nanocontainers can be produced with a controlled mean diameter and low
polydispersity compared to liposomes. They were tested and shown to be more
stable than liposomes.[1] These represent the main advantages with respect to the
application as carriers to improve the drug stability and the circulation life-time.
Another factor which could increase dramatically the circulation life-time and
therefore the availability of the encapsulated SOD, is the stealth property of the poly-
(2-methyloxazoline) chain, comparable to that of PEG. Besides, the polymer used for
this study, has an oxygen permeable membrane, as will be shown later. All these
advantages make the nanoreactors a completely new approach of drug delivery
systems, in which the cargo is not released, but performs its function within the
vesicle.
The nanovesicles, made of poly-(2-methyloxazoline)-poly (dimethylsiloxane)-poly (2-
methyloxazoline), successfully encapsulated the SOD protein during their formation
by a self-assembling process, as proved by confocal laser-scanning microscopy and
fluorescence-correlation spectroscopy. Electron paramagnetic resonance
spectroscopy and circular dichroism analyses showed that no structural changes
appeared within the proteins once inside the inner cavity of the nanovesicles. The
function of this antioxidant nanoreactor was tested by pulse radiolysis which
demonstrated that superoxide dismutase remains active inside the nanovesicles.
This simple and robust hybrid system provides selective shielding of a sensitive
enzyme from proteolytic attack and therefore points to a new direction for developing
drug delivery applications.