Single component chitosan hydrogel microcapsule from a layer-by-layer approach.

Smart biomaterials have found broad applications in modern medical technologies.1 However, the development of smart hydrogels with rapid response, good biocompatibility, and controllable degradability is still a formidable challenge. Chitosan, a biodegradable, nontoxic, and renewable linear polysaccharide, has been considered for various biomedical and pharmaceutical applications.2,3 To these ends, microparticles of chitosan in hundreds of micrometers have been prepared in different ways, including coacervation/ precipitation, spray-drying, emulsion cross-linking, emulsiondroplet coalescence, reverse micellization, ionic gelation, and sieving method.3,4 Complexation between chitosan and oppositely charged polysaccharides in solution is another way to synthesize chitosan microparticles; however, this process often leads to the formation of fibers.5 A new strategy, the so-called “layer-by-layer (LbL) assembly”, has been used here to fabricate microcapsules from chitosan. This strategy, based on the electrostatic interaction between oppositely charged polyelectrolytes, was first introduced by Decher et al. to fabricate thin films on planar supports by alternate adsorption of polycation and polyanion.6 Because of its advantages of fine control of the compositions and the thickness of the capsules, the LbL method received more and more attention in recent years.7-9 It was extended to three-dimensional (3D) systems by Mohwald et al. to fabricate core-shell particles and hollow capsules by further removal of the sacrificial core.10 In previous works, we first extended the LbL method based on hydrogen and covalent bonding to 3D systems and synthesized hydrogen or covalent bonded capsules.11,12 Chitosan bears positive charges and is a polycation at low pH. It has been used widely to fabricate LbL films13-19 and capsules20-22 with other polyelectrolytes. For the normal LbL methods, the capsule wall has at least two compositions. In certain applications, one may take advantage of the feasibility of several components by combining their individual material properties. On the other hand, the presence of a second polymer component for LbL assembling may limit the specific functionality of materials. For instance, the biocompatibility and biodegradability of chitosan could be destroyed by a second polymer component. Moya et al. fabricated a nearly single component capsule of polyallylamine hydrochloride (PAH) from the polystyrene sulfonate (PSS)/PAH LbL assembly by using cells as the template.23 The PAH in the capsule wall was oxidized and cross-linked, and then most of PSS was removed while removing the cell core template with sodium hypochlorite. However, this strategy could not be a general method for fabrication of single component capsules. Zhang et al. reported the preparation of single component 2-dimensional films from hydrogen-bonded LbL films, but these films were not cross-linked.24,25 Our new strategy is to selectively crosslink the chitosan chains and remove the second polymer component that was built up in the capsule walls (see Scheme 1). Using this strategy, single component chitosan hydrogel microcapsules were successfully synthesized. The pHresponsive volume phase transition of the chitosan hydrogel microcapsules could be controlled through the cross-linking density. The resultant chitosan gel microcapsules are nearly monodispersed, and the shell thickness is tunable, which is a big advantage to control the releasing kinetics of encapsulated drug or other molecules in response to pH or salt concentration changes. More importantly, although many shell cross-linked capsules have been made from synthetic block copolymers through a strategy of self-assembly of block copolymers with selective cross-linking on the shell block,26-31 it is very challenging, if not impossible, to synthesize well-defined block copolymers from natural polysaccharides. Our novel strategy here can provide a general method to synthesize shell cross-linked microcapsules from natural polysaccharides that have many applications in the pharmaceutical and medical field due to their biocompatibility and degradability.