Oral chemotherapy is a key step towards ‘chemotherapy at home’, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.
Poly(l-lactide-co-caprolactone) (PLCL, 50:50) has been used in cartilage tissue engineering because of its high elasticity. However, its mechanical properties, including its rigidity and viscoelasticity, must be improved for compatibility with native cartilage. In this study, a set of PLCL/poly(l-lactic acid) (PLLA) blends was prepared by blending with different mass ratios of PLLA that range from 10 to 50%, using thermoplastic techniques. After testing the properties of these PLCL/PLLA blends, they were used to fabricate scaffolds by the 3D printing technology. The structures and viscoelastic behavior of the PLCL/PLLA scaffolds were determined, and then, the potential application of the scaffolds in cartilage tissue engineering was evaluated by chondrocytes culture. All blends demonstrate good thermal stability for the 3D printing technology. All blends show good toughness, while the rigidity of PLCL is increased through PLLA blending, and Young’s modulus of blends with 10–20% PLLA is similar to that of native cartilage. Furthermore, blending with PLLA improves the processability of PLCL for 3D printing, and the compression modulus and viscoelasticity of 3D-printed PLCL/PLLA scaffolds are different from that of PLCL. Additionally, the stress relaxation time (t1/2) of the PLCL/PLLA scaffolds, which is important for chondrogenesis, is dramatically shortened compared with the pure PLCL scaffold at the same 3D-printing filling rate. Consistently, the PLCL90PLLA10 scaffold at a 70% filling rate with much shorter t1/2 is more conducive to the proliferation and chondrogenesis of in vitro seeded chondrocytes accompanied by upregulated expression of SOX9 than the PLCL scaffold. Taken together, these results demonstrate that blending with PLLA improves the printability of PLCL and enhances its potential application, particularly PLCL/PLLA scaffolds with a low ratio of PLLA, in cartilage tissue engineering.