Assembly Of Pnipam-based Nanogels Into Nanoscale Pickering Emulsion And Their Application In Drug Delivery

Assembly of nanoparticles as interfacial stabilizer at oil-in-water (O/W) interfaces for Pickering emulsions is an intriguing focus in the fields of chemical industry, material sciences and so on. However, it is still a major challenge to fabricate nanoscale Pickering emulsion with nanoparticles assembleing at O/W interfaces and to apply potential in nanomedicine. Nanogels as nanoscale polymer materials possess the characteristics of hydrogel and nanoparticles. P(NIPAM-co-AA) nanogels were synthesized by the method of emulsifier-free polymerization, which displayed significant deformability of swelling-shrinkage responding to external stimulus. A nanoscale Pickering emulsion was fabricated with the nanogels assembling at O/W interfaces, of which the stabilization mechanism was explored. This approach provided a novel strategy to fabricate nanoscale Pickering emulsions using deformable nanogel particles for cancer drug delivery and controlled drug release. The main research results are summarized as follows:(1) Thermo- and pH sensitive P(NIPAM-co-AA) nanogels were synthesized by emulsifier-free polymerization with N-isopropylacrylamide and allylamine as functional monomers. To investigate the structure, morphology and other physico-chemical properties, the nanogels were characterized by NMR, FT-IR, PCS, elemental analysis and TEM. The results indicated that the nanogels exhibited significant deformability of swelling-shrinkage responding to temperature and pH when the dose of chemical cross-linker was low. What's more, it was expected that the shrinkage capacity of the nanogels could provide a possibility to compress the assembly of nanogels at O/W interfaces and to stabilize nanoscale Pickering emulsion.(2) A nanoscale Pickering emulsion was fabricated with the deformable nanogels assembling at O/W interfaces at the condition of energy input. The morphology and distribution of nanogels at O/W interfaces were characterized by fluorescent probe and TEM. Then the stabilization mechanism of the nanoscale Pickering emulsion stabilized by nanogels was explored. It was elucidated that both the hydrogen bonding between the nanogels and the amphipathic properties played an important role on the stability of the nanoscale emulsions. In the all, this approach provided a novel universal strategy to fabricate nanoscale Pickering emulsions using deformable nanogel particles for cancer drug delivery and controlled drug release.(3) Paclitaxel was selected as a model anti-cancer drug to demonstrate the potential of the nanoscale Pickering emulsion stabilized by the nanogels for drug delivery. It was indicated that the nanoscale Pickering emulsion as drug carrier was found to provide sustained drug release. The paclitaxel from the nanoscale Pickering emulsion enhanced the inhibition to A2780 cell, and the paclitaxel-free Pickering emulsion showed no significant cytotoxicity. Furthermore, in vivo pharmacokinetic behavior of paclitaxel-loaded nanoscale Pickering emulsion was evaluated, with a result of prolonged in vivo blood circulation time. Compared with commercial drug Taxol, AUC0~∞value of paclitaxel-loaded nanoscale Pickering emulsion was 4.9 times higher and t1/2βwas 8.3 times longer. It was also implied that the nanoscale Pickering emulsion stabilized by nanogels could achieve long circulation effect.(4) Anti-tumor efficacy studies and the tissue distribution of paclitaxel-loaded nanoscale Pickering emulsion were investigated in the ovarian carcinoma A2780 subcutaneous model mice. Compared with Taxol group, the nanoscale Pickering emulsion administration group displayed a more obvious tumor regression. The results of tissue distribution showed that nanoscale Pickering emulsion significantly enhanced accumulation of drug at tumor tissue and liver, which might attribute to the enhanced permeability retention (EPR) effect and the longer half-life time of the nanoscale Pickering emulsion. It was concluded that there was a potential to utilize the nanoscale Pickering emulsion stabilized by nanogels as a passively targeting cancer carrier.In conclusion, thermo- and pH sensitive P(NIPAM-co-AA) nanogels were synthesized with molecular designing. Nanoscale Pickering emulsion was fabricated with the deformable nanogels assembling at O/W interfaces, and the stabilization mechanism of the nanoscale Pickering emulsion stabilized by nanogels was explored. This approach provided the potential of the nanoscale Pickering emulsion for cancer drug delivery with long blood circulation and passively targeting cancer.