Effects of stereo-regularity of multiblock co-poly(rac-lactide)s on stereo-complex microparticles and their insulin delivery.

Uniform stereo-complex microparticles ranging from nanometer to micrometer size are prepared by using stereo multiblock co-poly(rac-lactide)s (smb-PLAs) with different stereo-regularity. At comparable molecular weights, as the smb-PLA stereo-regularity decreases from 88% to 76%, the crystallinity of the microparticles decreases noticeably, as proved by DSC and WAXD. At the same time, the shape of the microparticles varies from the flower shape to the sphere shape and the particle size increases markedly from 700-2700 nm as shown by SEM. However, all insulin-loaded microparticles are of cake-shape and their sizes depend on the stereo-regularity. The crystallization of smb-PLAs facilitated by insulin is evidenced by the increase of T(m) and DeltaH(f) in DSC. The highest insulin-loading content of 14.2% and -entrapment efficiency of 82.8% are obtained from the smb-PLA with the highest stereo-regularity of 88%. Release studies in vitro show the least first-day release at about 25% followed by continuous release of another 70% of insulin over one month. Stereo-complex microparticles of smb-PLAs with lower stereo-regularity resulted in a relatively lower insulin-entrapment efficiency and -loading content, a larger first-day release, and also complete release of 90% of the total amount within one month. The release system follows a diffusion mechanism. By contrast, atactic PLA shows a very low entrapment efficiency of 16.7%. Structure of a stereo multiblock co-poly(rac-lactide).

Formation of flower- or cake-shaped stereocomplex particles from the stereo multiblock copoly(rac-lactide)s.

Flower- or cake-shaped particles with uniform particle size ranging from nanometers to micrometers were prepared from the stereo multiblock copoly(rac-lactide)s (smb-PLAs) by precipitating the polymer from its solution in methylene chloride/ethanol via three different methods: slowly lowering the solution temperature, slowly evaporating the solvent, and slowly adding a nonsolvent. Under the same condition, sheet-shaped crystals in 10 mum size but not particles were obtained from the pure PLLA with almost the same molecular weight. Electron diffraction and WAXD data demonstrated that the stereocomplex particles belonged to the monoclinic system. All three methods resulted in particles with identical morphology and almost the same particle size. At a given stereoregularity of 88%, as the molecular weight of the polymer increased from 8700 to 23,200 Da, the crystallinity decreased, the particle morphology changed from flower-shaped to cake-shaped, and the diameter and height of the particles increased from 0.8 and 0.45 to 3.6 microm and 2.0 microm, respectively. The initial concentration of the polymer solution influenced the particle size slightly but affected the morphology markedly. On the basis of the above experimental observations, it was proposed that the smb-PLA particles of flower- or cake-shape were formed in four steps: (1) complexation in solution of the smb-PLA chains; (2) particle nucleation; (3) particle growth in the width direction; and (4) particle growth in the height direction. The curvature of the paired smb-PLA chains and the inner stress governed the particle size, and the interconnection between the neighboring particles determined the layered structure and the package density of the particles formed.

Hydroxyapatite surface modified by L-lactic acid and its subsequent grafting polymerization of L-lactide.

A new method of surface modification of hydroxyapatite nanoparticles (n-HA) by surface grafting reaction of l-lactic acid and ring-opening polymerization of l-lactide (LLA) was developed. Two modified HA nanoparticles were obtained: HA modified by l-lactic acid (l-HA) and HA grafting with poly(l-lactide) (PLLA; p-HA). The modified surface of n-HA was attested by Fourier transformation infrared, (31)P MAS NMR, and thermal gravimetric analysis. The results showed that l-lactic acid could be easily grafted onto the n-HA surface by forming a Ca carboxylate bond and initiated by the hydroxyl group of the grafted l-lactic acid and LLA could be graft-polymerized onto the n-HA surface in the presence of stannous octanoate. The highest grafting amounts of l-lactic acid and PLLA were about 33 and 22 wt %, respectively. The modified HA/PLLA composites showed good mechanical properties and uniform microstructure. The tensile strength and modulus of the p-HA/PLLA composite containing 15 wt % of p-HA were 67 MPa and 2.1 GPa, respectively, while those of the n-HA/PLLA composites were 45 MPa and 1.7 GPa, respectively. The elongation at the break of the l-HA/PLLA composite containing 15 wt % l-HA could reach 44%, in comparison with 6.5% of the n-HA/PLLA composites containing 15 wt % n-HA.

Nano-composite of poly(L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility.

In order to improve the bonding between hydroxyapatite (HAP) particles and poly(L-lactide) (PLLA), and hence to increase mechanical properties of the PLLA/HAP composite as potential bone substitute material, the HAP nano-particles were surface-grafted with PLLA and further blended with PLLA. The structure and properties of the composites were subsequently investigated by the mechanical property testing, the differential scanning calorimeter measurements (DSC), the scanning electron microscopy (SEM), the polarized optical microscopy (POM), and the cell culture. The PLLA molecules grafted on the HAP surfaces, as inter-tying molecules, played an important role in improving the adhesive strength between the particles and the polymer matrix. At a low content (approximately 4 wt%) of surface grafted-HAP (g-HAP), the PLLA/g-HAP nano-composites exhibited higher bending strength and impact energy than the pristine PLLA, and at a higher g-HAP content (e.g., 20 wt%), the modulus was remarkably increased. It implied that PLLA could be strengthened as well as toughened by g-HAP nano-particles. The results of biocompatibility test showed that the g-HAP existing in the PLLA composite facilitated both adhesion and proliferation of chondrocytes on the PLLA/g-HAP composite film.