Stimulus-responsive Layer-by-layer Multilayers For Controlled Drug Delivery

In recently decades, stimuli-responsive ultrathin films assembled vialayer-by-layer (LbL) fashion are finding a rising number of applications in surfacebiofunctional coatings, biological sensors, nano reactors and drug delivery. Owing toits highly specific and high efficiency performances, supramolecular drug-loadingapproachbased on LbL platforms becomesa new development direction in the field ofcontrolled drug release system. Although remarkable reports on stimuli-responsiveLbL multilayersbysupramolecular drug-loading approach for drug release have beenpresented, their application in the surface of biomaterials is scarce and the studies inthis direction move slowly. On the other hand, almost all of research is mainlyfocusing on the design of single-response LbL multilayers, however, relatively fewreports established multi-responsive drug delivery based on LbL platform. Herein, wedesigned and synthsised novel light-response multilayer films by supramoleculardrug-loading approach on the surface of shape-memory poly(D,L-lactic acid), andpresented multi-responsive drug delivery system, and investigated their controlleddrug release properties.In Chapter1,we present a detailed review about recent progress of LbLtechnology, stimuli-responsive LbL films and their applications in controlled drugdeliveryfields.In Chapter2, we design and synthesis a light-controlled multilayers bycombining precursor assembly and LbL deposition. Our research strategy to fabricatea photoresponsive LbL system involves following steps: i) inclusion complex ofAzo-modified poly(acrylic acid) and α-CD-modified drug template is formed inaqueous solution, following the concept of precursor assembly; ii) a photo-switchablemultilayer film is then fabricated by alternating deposition of the inclusion complex(polyanion) andchitosan (Chi, polycation) viaelectrostatic LbL technology on thesurface of the amino-silanized quartz slide.UV-vis were employed to monitorassembly process ofAzo/Chi multilayer films. Subsequently, a shape-memory LbL (SMLbL)multilayered material was establishedby applying LbL coating technology toa new shape-memory poly(D,L-lactic acid)(PDLLA) we prepared. Since theinteractions between α-CD and Azo were photo-sensitive, the multilayers couldrelease the model drug (α-CD-RhB) with the irradiation of UV light. Thephoto-sensitivity of the multilayer films was studied throughconfocal laser scanning microscopy and atomic force microscopy (AFM). Finally,Degradation experiments of multilayers-coated PDLLA in vitrosuggested that drugwas gradually released into the incubation solutions for4-10weeks,accompanying thelager mass loss of PDLLA materials. Such novel designs and methods, we believe,should prove to be useful for the development of multifunctional biomaterials.In Chapter3, we design and synthesis a multi-responsive drug release platformof hydrogen-bonding multilayers which involves biologically compatible PEGylatednanoparticles (NPs) and Azo polyelectrolytes loadingα-CD modified drug viahost–guest interaction. Firstly, PEGylated NPs were prepared via thethiol–maleimide“click” reaction andtheir structure andmorphology were characterized using Ramanspectroscopy, dynamic light scattering and transmission electron microscopy. Thealternating deposition ofPEGylated NPs and drug-loading Azo throughhydrogen-bonding self-assembly technologyleaded to multilayeredcoatings. UV-visspectrum, water contact angle measurement and AFM were used to monitoredmultilayers formation, respectively. The obtained films were able to release drugs in alight-controlled manner due to the stimuli-sensitive nature of Azo. Meanwhile, wedemonstrate that the films could be rapidly deconstructed to simultaneously releasedrugs and NPs upon exposure to physiological conditions because of the pH-erasablecharacteristics of hydrogen-bonding. In additional, we found the multilayer films werealso sensitive to salt, thereby making it possible to tunethe release of drugs bychanging the ionic strength of solution. Overall, the results of our work demonstratethat the multilayer film exhibited multi-responsive drug release properties. With thesesmart features, thesemultilayers will find wide application inappropriatebiomedicalfields.