ABSTRACT
Polyurethane nanomicelle is a promising functional drug delivery system. In this work, the polyurethane (P3-PU) was synthesized from PLGA1200-PEG1450-PLGA1200 (P3, a thermosensitive and biodegradable triblock copolymer) and L-lysine ester diisocyanate (LDI). Then, reactive benzaldehyde was further imported to terminate P3-PU to obtain benzaldehyde modified polyurethane (P3-PUDA). The micelles, temperature-sensitive P3-PU nanomicelle and P3-PUDA nanomicelle, were systematically investigated, including the size, stability, temperature sensitivity, drug loading and release behavior, cytotoxic on human hepatocytes (L02), and inhibitory effect on human hepatocellular carcinoma cells (HepG2). The results show the thermosensitive behavior of the micelles can be adjusted by the terminal group. The polyurethane micelles with a uniform size between 20 nm and 30 nm showed excellent stability and good biocompatibility to L02 cells. Besides, in vitro experiments showed that Dox-loaded P3-PUDA micelles exhibited faster and higher release rate at 37 °C and better inhibitory effect on HepG2 than the Dox-loaded P3-PU micelles. Moreover, the achieved benzaldehyde modified polyurethanes also provides various possibilities to adjust further to enlarge its applications. Therefore, the polyurethane micelles will have great potential in the field of drug carriers.
Subject(s)
Micelles , Polyurethanes , Doxorubicin , Drug Carriers , Drug Delivery Systems , Humans , Polyesters , Polyethylene GlycolsABSTRACT
Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.
Subject(s)
3-Mercaptopropionic Acid/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Chitosan/analogs & derivatives , Chitosan/chemistry , Hydrogels/chemistry , Hydrogen-Ion Concentration , Polyethylene Glycols/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Disease Models, Animal , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Drug Carriers , Drug Liberation , Humans , Mice , Molecular Structure , Xenograft Model Antitumor AssaysABSTRACT
The mechanical and biodegradable properties of hydrogels are two essential properties for practical biomaterial applications. In this work, a series of biodegradable polyurethane (PU) hydrogels were successfully synthesized using two kinds of triol crosslinkers with different chain structures. One crosslinker is normal glycerol (GC) with short chain length, and the other is biodegradable poly (ε-caprolactone)-triol (CAPA) with long chain length. All PU hydrogels showed considerable water uptake around ~60%, excellent strength (above 3 MPa), advisable modulus (0.9~1.7 MPa), high elasticity (above 700%), as well as good biodegradability and biocompatibility. Hydrogen bonds served as reversible sacrificial bonds in the PU hydrogels endow them good toughness with partial hysteresis during deformation. The biodegradable long chain crosslinker CAPA can certainly accelerate the degradation of PU hydrogels compared with the GC crosslinked hydrogels. The degradation of these hydrogels was a process of continuous erosion from the surface to interior, which contributes to the high remain of mechanical properties after 30 days-degradation. Besides, the hydrogels also show excellent antifouling ability of protein and anti-adhesion of cells. Therefore, these hydrogels suggest great potential used as biological anti-adhesive membranes or catheters.
