Xi-Li Lu

The application of poly (glycerol-sebacate) as biodegradable drug carrier

Poly (glycerol-sebacate) (PGS) is an elastomeric biodegradable polymer which possesses the ideal properties of drug carriers. In the present study, we prepared a series of PGS implants (5-FU-PGSs) loaded with different weight percent of 5-fluorouracil (2, 5, 7.5 and 10%). We studied the infrared spectrum properties, in vitro degradation and drug release, in vivo degradation and tissue biocompatibility of 5-FU-PGSs, in order to provide detailed information for the application of PGS as biodegradable drug carrier in cancer therapy. Macroscopically, all 5-FU-PGS wafers in phosphate buffer solution (PBS) kept their geometries during the degradation period of 30 days. The in vitro degradation rates of 5-FU-PGSs were accelerated when higher concentration of 5-FU was doped. Scanning electron microscopy observation showed that the surfaces of 5-FU-PGSs with higher concentration of 5-FU had irregular pits. The cumulative drug release profiles of 5-FU-PGSs exhibited a biphasic release with an initial burst release in the first day. After 7 days, almost 100% cumulative release of 5-FU was found for all 5-FU-PGSs.The degradation rate of 5-FU-PGSs in vivo was much quicker than that in vitro. Hematoxylin and eosin staining showed that no remarkable inflammations were observed in the tissue surrounding 5-FU-PGS implants, suggesting 5-FU-PGSs had good biocompatibility and no tissue toxicity. In vitro anti-tumor activity assay suggested that 5-FU-PGSs exhibited anti-tumor activity through sustained-release drug mode. These results demonstrate that PGS is a candidate of biodegradable drug carriers.

Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid)

The development of biodegradable materials with controllable degradation properties is beneficial for a variety of applications. Poly(glycerol-sebacate) (PGS) is a promising candidate of biomaterials; so we synthesize a series of poly(glycerol, sebacate, glycolic acid) (PGSG) with 1:2:0, 1:2:0.2, 1:2:0.4, 1:2:0.6, 1:2:1 mole ratio of glycerol, sebacate, and glycolic acid to elucidate the relation of doped glycolic acid to the degradation rate and mechanical properties. The microstructures of the polymers with different doping of glycolic acid were dissimilar. PGSG with glycolic acid in the ratio of 0.2 displayed an integral degree of ordering, different to those with glycolic acid in the ratio of 0, 0.4, 0.6, and 1, which showed mild phase separation structure. The number, DeltaH(m), and temperature of the PGSG melting peaks tended to decrease with the increasing ratio of doped glycolic acid. In vitro and in vivo degradation tests showed that the degradation rate of PGSG with glycolic acid in the ratio of 0.2 was slowest, but in the ratio range of 0, 0.4, and 0.6, the degradation rate increased with the increase of glycolic acid. All PGSG samples displayed good tissue response and anticoagulant effects. Our data suggest that doping glycolic acid can modulate the microstructure and degree of crosslinking of PGS, thereby control the degradation rate of PGS.

Biodegradable shape memory nanocomposites with thermal and magnetic field responsiveness

Thermal and magnetic field responsive biodegradable shape memory polymer nanocomposite was prepared with Fe3O4 nanoparticles and poly(L-lactides) (PLLA). The magnetic Fe3O4 nanoparticles with an average size of 9 nm were initially synthesized by co-precipitation method and then followed by surface modification using oleic acid. The TEM and SEM results show that the surface modified Fe3O4 nanoparticles can evenly disperse in chloroform and PLLA polymer matrix. The tensile test results show that the addition of Fe3O4 nanoparticles to a PLLA matrix greatly improved the elastic modulus, tensile strength, elongation at break, and the shape memory properties as well. Moreover, the shape recovery process of the nanocomposites driven by an alternating magnetic field was also observed. However, the shape recovery ratio and the recovery speed in an alternating magnetic field are lower than that occurred in 70 °C water. The lower shape recovery ratio and the recovery speed in an alternating magnetic field is attributed to the low frequency and strength of the magnetic field, which lead to small heat generated by Fe3O4 nanoparticles.

A poly(glycerol–sebacate–curcumin) polymer with potential use for brain gliomas

Curcumin has multiple biological and pharmacological activities, including antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and antitumor activities. However, the clinical use of curcumin is limited because of its poor oral absorption and extremely poor bioavailability. In order to overcome these limitations, we conjugate curcumin chemically into the known biocompatible and biodegradable polymer, poly(glycerol-sebacate), and prepare the unitary poly(glycerol-sebacate-curcumin) polymer. The structure, the in vitro degradation, the drug release, and antitumor activity as well as the in vivo degradation and tissue biocompatibility of poly(glycerol-sebacate-curcumin) polymer are investigated. The in vitro degradation and drug release profile of poly(glycerol-sebacate-curcumin) are in a linear manner. The in vitro antitumor assay shows that poly(glycerol-sebacate-curcumin) polymer significantly inhibits human malignant glioma cells, U87 and T98 cells. In view of the cytotoxicity against brain gliomas, local use of this polymer would be a potential method for brain tumors.

A poly(glycerol-sebacate-(5-fluorouracil-1-acetic acid)) polymer with potential use for cancer therapy

In this study, 5-fluorouracil-1-acetic acid was chemically conjugated with poly(glycerol-sebacate) (PGS) to form a unitary polymer poly(glycerol-sebacate- (5-fluorouracil-1-acetic acid)) (PGS-5-FU-CH2COOH). The structure, the in vitro antitumor activity of 5-FU-CH2COOH, the in vitro degradation, the drug release, and antitumor activity as well as the in vivo degradation and tissue biocompatibility of PGS-5-FU-CH2COOH were investigated. The 5-FU-CH2COOH inhibited HeLa (human cervical cancer cell line) and SGC-7901 (human gastric adenocarcinoma cell line) tumor cells with a half maximal inhibitory concentration (IC50) of 0.196 and 0.267 μM, respectively, after a 3-day incubation. The in vitro drug release profiles of PGS-5-FU-CH2COOH exhibited a biphasic release with an initial exponential phase in the first week and then the second constant linear phase. An in vitro antitumor assay of the PGS-5-FU-CH2COOH polymer showed significant cytotoxicity against tumor cells. The implanted PGS-5-FU-CH2COOH degraded completely in 1 month after implantation. The antitumor activity and improved drug release profile of PGS-5-FU-CH2COOH indicate its potential as an implantable polymer for cancer therapy.

Characterization and optimization of glycerol/sebacate ratio in poly(glycerol-sebacate) elastomer for cell culture application.

Poly(glycerol-sebacate) (PGS) is an elastomeric biodegradable polyester. Our previous series of studies have showed that PGS has good biocompatibility. In view of the potential use of PGS in bioengineering, we attempt to characterize the PGS polymer with different ratio of glycerol and sebacic acid, and the cell adhesion and growth on these polymers. PGSs with different proportion of glycerol and sebacic acid were synthesized by polycondensation reaction. The microstructure of the series PGSs were characterized by infrared spectroscopy and X-ray diffraction analysis (XRD). Results showed that, with the increase of the ratio of sebacic acid in PGS from 1:0.8, 1:1, to 1:1.2 (ratio of glycerol to sebacic acid), the main diffraction peak in XRD, the sol content and gel swelling increased but then decreased, suggesting that the degree of crosslinking and the inherent degree of order of the series PGS increased and then decreased. With the increase of sebacic acid proportion, water absorption increased and then decreased, and the water absorption ranged from 9.62% to 10.66%. The mass loss of the series of samples in degradation experiments ranged from 24.63% to 40.06% on the 32nd day of degradation. Cell culture data suggested that the polymer with the ratio of 1:0.8 for glycerol and sebacate was suitable for cell adhesion and growth. In conclusion, PGS can be used as the cell culture matrix by modifying the composition ratio of glycerol and sebacic acid to improve the properties of cell adhesion and growth.

The Polycondensing Temperature rather than Time Determines the Degradation and Drug Release of Poly(Glycerol–Sebacate) Doped with 5-Fluorouracil

Poly(glycerol–sebacate) (PGS) is an elastomeric biodegradable polyester that could be used as biodegradable drug carrier. We have previously prepared PGS implants doped with 5-fluorouracil (5-FU-PGSs) and found that 5-FU-PGSs exhibited an initial burst of 5-FU release during in vitro degradation. The synthesis temperature and time are two of the most important reaction conditions for polymer synthesis. Therefore, in order to establish a controllable drug-release manner, we prepared a series of 5-FU-PGS with 2% weight of 5-FU under synthesis conditions with different polycondensing temperature and time and characterized the infrared spectrum properties, in vitro degradation and drug release. Results showed that the polycondensing temperature determined the mechanical properties, degradation and drug release of 5-FU-PGSs. With the polycondensing temperature increasing, the elastic modulus and hardness of 5-FU-PGSs increased, and the mass loss and 5-FU release rate decreased. The polycondensing time had no significant influence on the mechanical property, degradation and drug release of 5-FU-PGSs. We suggest that the polycondensing temperature is the factor to control the drug-release manner.