Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

具有三层管壁结构组织工程血管支架的生物力学性能

目的针对组织工程血管的体内培养技术路线，对所制备的具有三层管壁结构的组织工程血管支架的生物力学性能进行测试，并研究了壁厚对支架力学性能的影响，以保证后续的动物体内移植实验能顺利进行。方法采用涂敷，喷涂．滤沥的方法制备了具有三层管壁结构（多孔PLGA层．致密PU层．多孔PLGA层）的可降解组织工程血管支架，用自制的设备测试了其爆破强度和径向顺应性，并对血管支架进行了缝合强度的测试。结果所制备的厚度为0．295mm-0．432mm的三层结构血管支架的径向顺应性为3．80％／100mmHg-0．57％／100mmHg，爆破强度为160kPa～183kPa，缝合强度为0．63N／针～1．52N／针。结论支架的管壁厚度，尤其是中间层厚度，对支架的力学性能有重要影响。增大壁厚可导致径向顺应性急剧下降，爆破强度和缝合强度线性提高。在所制备的样品中，管壁厚度为0．295mm的支架其综合力学性能最优，可满足血管组织工程体内植入的力学性能要求。     

Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.     

In Vivo Evaluation of a Colon-Specific Drug Delivery System: An Absorption Study of Theophylline from Capsules Coated with Azo Polymers in Rats

Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coatings for colon-specific drug delivery. The gastrointestinal absorption of theophylline from capsules coated with the azo polymers was examined in the proximal part of the small intestine and the cecum of male Wistar rats. The capsules were surgically inserted in the region of interest. The plasma concentration of the drug was higher when the capsules were inserted in the cecum as compared to the small intestine. The appearance of theophylline in the plasma when capsules were administered in the small intestine can be attributed to simple diffusion of the drug through the swollen polymer coating. Release and absorption from the cecum is the combined result of diffusion and degradation of the azo polymer coatings by bacterial azo reductase.     

可生物降解的注射用药物传递系统研究进展

目的在大量文献的基础上对可注射的体内半固态药物传递系统进行综述 ,指出它们作为局部植入药物传递系统所存在的优、缺点及其前景。方法根据在体内获得固态化的机制不同 ,介绍形成这些系统的不同方法及类型。结果与结论这些系统主要是由可生物降解材料制成的 ,具有生物相容性好、应用方便、可局部给药、延缓药物释放等优点 ,促进了新型药物传递系统的发展     

Cellular uptake and concentrations of tamoxifen upon administration in poly(ε-caprolactone) nanoparticles

Purpose: In an attempt to increase the local concentration of tamoxifen in estrogen receptor positive breast cancer cells, we have prepared and characterized poly (ε-caprolactone) (PCL) nanoparticle formulation. Methods: PCL (mol wt 14,800 daltons) nanoparticles were prepared by the solvent displacement method in acetonewater system in the presence of Pluronic F-68. PCL nanoparticles, labeled with rhodamine 123, were incubated with MCF-7 estrogen receptor positive breast cancer cells to determine uptake, intracellular distribution, and localization as a function of time. Intracellular drug concentrations over a specified period of time using different initial doses were examined using tritiated [³H]-tamoxifen. Results: A significant fraction of the administered rhodamine 123-loaded PCL nanoparticles was found in the perinuclear region of the MCF-7 cells, where estrogen receptors are also localized, after 1 hour of incubation. Measurements of the intracellular concentrations revealed that most of the administered nanoparticle dose was internalized within the first 30 minutes of incubation, and the uptake followed saturable transport kinetics. Conclusion: Results of this study show that PCL nanoparticles were rapidly internalized in MCF-7 cells and intracellular tamoxifen concentrations followed a saturable process. This approach may provide better therapeutic benefit by delivering the drug locally, near the tumor cells, for a longer period of time.     

Biocompatibility of Zinc Matrix Biodegradable Composites Reinforced by Graphene Nanosheets

As a new type of biodegradable implant material, zinc matrix composites have excellent potential in the application of biodegradable implants because of their better corrosion resistance than magnesium matrix materials. Our previous studies have shown that graphene nanosheet reinforced zinc matrix composites (Zn-GNS) prepared by spark plasma sintering (SPS) have good mechanical properties and suitable degradation rate. However, the biocompatibility of zinc matrix composites is still a problem of concern. The cytocompatibility and blood compatibility of pure zinc and Zn-GNS composites in vitro were studied. The results showed that Zn-GNS composites had acceptable toxicity to MG-63 human osteosarcoma cells. In addition, the hemolysis rate of pure zinc and its composites were less than 3%, which has no adverse effect on adhered platelets, and has good antithrombotic and antiadhesion platelets properties. In conclusion, the addition of GNS did not adversely affect the biocompatibility of Zn-GNS composites, which indicated that Zn-GNS composites are a promising candidate for bone implantation.     

Biodegradable Polymer Nanosheets Incorporated with Zn-Containing Nanoparticles for Biomedical Applications

So far, poly(L-lactic acid), PLLA nanosheets proved to be promising for wound healing. Such biodegradable materials are easy to prepare, bio-friendly, cost-effective, simple to apply and were shown to protect burn wounds and facilitate their healing. At the same time, certain metal ions are known to be essential for wound healing, which is why this study was motivated by the idea of incorporating PLLA nanosheets with Zn²⁺ ion containing nanoparticles. Upon being applied on wound, such polymer nanosheets should release Zn²⁺ ions, which is expected to improve wound healing. The work thus focused on preparing PLLA nanosheets embedded with several kinds of Zn-containing nanoparticles, their characterization and ion-release behavior. ZnCl₂ and ZnO nanoparticles were chosen because of their different solubility in water, with the intention to see the dynamics of their Zn²⁺ ion release in liquid medium with pH around 7.4. Interestingly, the prepared PLLA nanosheets demonstrated quit similar ion release rates, reaching the maximum concentration after about 10 h. This finding implies that such polymer materials can be promising as they are expected to release ions within several hours after their application on skin.     

超高分子量聚D,L乳酸小夹板螺钉行颧弓骨折内固定的动物实验研究

目的：观察新型可吸收性骨夹板的骨内固定效果。方法：采用自身对照研究方法,用超高分子量生物降解材料聚Ｄ,Ｌ乳酸制作小夹板、螺钉内固定装置,对１０只狗进行颧弓骨折内固定,并与金属钛小夹板、螺钉内固定相比较。结果：对颧弓凹陷性骨折,分子量高达６０万ｋＤ以上的超高分子量聚Ｄ,Ｌ乳酸小夹板螺钉的机械性能足够维持骨段的稳定性并支撑其愈合。结论：聚Ｄ,Ｌ乳酸小夹板、螺钉同金属钛小夹板、螺钉内固定一样,对颧弓骨折具有良好的骨内固定效果,对骨折愈合过程无任何不良影响,其显著优点是无需二次手术取出。     

The effects of molecular structure on sol-to-gel transition of biodegradable poly(depsipeptide-co-lactide)-g-PEG copolymers

We report on the effects of number and length of PEG chains in poly(depsipeptide-co-dl-lactide)-g-poly(ethylene glycol) (P(DG-dl-LA)-g-PEG) copolymers on their sol-to-gel transition behavior. The graft-type copolymer is suitable for the systematic study of the effects of molecular structure and hydrophilic/hydrophobic balance on its sol-to-gel transition. We prepared various P(DG-dl-LA)-g-PEG copolymers through coupling reactions between the pendant carboxylic acid groups of P(GD-dl-LA) and the end hydroxyl group of MeO-PEG having various molecular weights. Temperature-responsive sol-to-gel transition of the obtained copolymer solution in phosphate-buffered solution (pH 7.4, ionic strength = 0.14) was investigated by the test tube inverting method and rheological measurements. P(GD-dl-LA)-g-PEG copolymer prepared from higher molecular weight PEG showed higher sol-to-gel transition temperatures compared with the copolymers prepared from lower molecular weight PEG, although these copolymers have similar weight content of PEG (23–24?wt.%). Similar trends were observed for groups of copolymers whose PEG contents were 27 or 30?wt.%. These results are informative for providing strategies on rational design of thermo-gelling polymers.