Characterization of the release profile of doxycycline by PLGA microspheres adjunct to non-surgical periodontal therapy

The aim of this pilot study was to assess the release of locally delivered doxycycline by poly (l-lactide-co-glycolide) (PLGA) microspheres in the periodontal pocket of patients with chronic periodontitis, treated by non-surgical periodontal therapy. Nineteen sites of non-adjacent teeth of four different patients were evaluated. Five milligram of PLGA microspheres loaded with 16 doxycycline hyclate (DOX) was administered per periodontal site. To quantify DOX released into the periodontal pocket, gingival crevicular fluid (GCF) was collected from the sites on days 2, 5, 7, 10, 15, and 20 after DOX application, and high-performance liquid chromatography was performed. Data were statistically assessed by ANOVA/Tukey test. At days 2, 5, and 7, the DOX concentration was stably sustained (23.33 ± 1.38, 23.4 ± 1.82, and 22.75 ± 1.33 μg/mL, respectively), with no significant differences over these assessment times (p > 0.05). At days 10 and 15, a tendency was observed toward a decrease in DOX concentration (21.74 ± 0.91 and 20.53 ± 4.88 μg/mL, respectively), but a significant decrease in GCF drug concentration (19.69 ± 4.70 μg/mL) was observed only on day 20. The DOX delivery system developed demonstrated a successful sustained release after local administration, as an adjunct to non-surgical periodontal therapy.     

Fabrication of a Layered Microstructured Polymeric Microspheres as a Cell Carrier for Nucleus Pulposus Regeneration

Abstract

This study aimed to investigate the feasibility of nanostructured 3D poly(lactide-co-glycolide) (PLGA) constructs, which are loaded with dexamethasone (DEX) and growth factor embedded hepaiin/poly(L-lysine) nanoparticles by a layer-by-layer system, to serve as an effective scaffold for nucleus pulposus (NP) tissue engineering. Our results demonstrated that the microsphere constructs were capable of simultaneously releasing basic fibroblast growth factor and DEX with approximately zero-order kinetics. The dual bead microspheres showed no cytotoxicity, and promoted the proliferation of the rat mesenchymal stem cells (rMSCs) by lactate dehydrogenase assay and CCK-8 assay. After 4 weeks of culture in vitro, the rMSCs- scaffold hybrids contained significantly higher levels of sulfated GAG/DNA and type-II collagen than the control samples. Moreover, quantity real-time PCR analysis revealed that the expression of disc-matrix proteins, including type-II collagen, aggrecan and versican, in the rMSCs-scaffold hybrids was significantly higher than the control group, whereas the expression of osteogenic differentiation marker type-I collagen was decreased. Taken together, these data indicate that the heparin bound bFGF-coated and DEX-loaded PLGA microsphere constructs is an effective bioactive scaffold for the regeneration of NP tissue.     

Development and characterization of oxaceprol-loaded poly-lactide-co-glycolide nanoparticles for the treatment of osteoarthritis

Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by double-emulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration.     

P LGA／P CL混纺技术改良P LGA电纺膜收缩性能的初步研究

目的：利用聚乳酸－聚乙醇酸共聚物／聚己内酯（ PLGA ／ PCL）混纺技术在不影响纯PLGA静电纺丝膜生物相容性的前提下改良其遇水收缩的缺陷,以使其操作性能更接近临床实际应用。方法：将不同重量比的PLGA ／ PCL（10∶0、7∶3、6∶4、5∶5及0∶10）混合,利用静电纺丝技术制得电纺膜,表征比较纺丝直径及收缩性。在相同条件下在膜上培养成骨细胞,比较不同电纺膜的细胞相容性,并在扫描电镜下观察不同电纺膜表面形貌及细胞粘附形态。结果：随PCL比例增加,纺丝直径有所增加,但在扫描电镜下不同电纺膜表面形貌及细胞粘附形态并无明显差异;加入PCL后混纺膜的细胞相容性较纯PLGA略有下降,但仍比纯PCL高,且不同比例的PLGA／PCL（7∶3、6∶4、5∶5）混合电纺膜细胞相容性无统计学差异;纯PLGA膜呈现极大的收缩比率,随PCL的添加收缩比率明显下降,且不同的添加比例组间无明显差异。结论：在PLGA中添加一定比例的PCL可以有效改善纯PLGA膜的收缩性能,且PCL的加入对PLGA良好的生物相容性影响较小。     

Calcium phosphate/poly(D,L-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect

Objectives: The present study aimed to provide temporal information on material degradation and bone formation using composite (C) bone defect filler materials consisting of calcium phosphate cement (CaP) and poly(d ,l ‐lactic‐co‐glycolic acid) (PLGA) microparticles (20 or 30 wt%) in rat critical‐sized cranial defects. Materials and methods: Critical‐sized bicortical cranial defects were created in 48 rats and CaP/PLGA cement composites were implanted for 4, 8 and 12 weeks (n=8). Results: Histological analysis of the retrieved specimens revealed that implant degradation was significantly faster for C30% (remaining implant up to 89.4 ± 4.4% at 12 weeks) compared with C20% (remaining implant upto 94.8 ± 2.1% at 12 weeks), albeit that overall degradation was limited. Although bone formation was limited in both experimental groups (upto 685765.9 μm² for C20% vs. 917603.3 μm² for C30%), C30% showed a significant temporal increase of total bone formation. The percentage of defect bridging was comparable for C20% and C30% at all implantation periods (range 40 ± 25.5% at week 4 to 65 ± 20% at week 12 for C20%; range 51.8 ± 7.8% at week 4 to 70.5 ± 16.2% at week 12 for C30%). Conclusion: The amount of PLGA‐microparticles in the CaP/PLGA cement composites demonstrated acceleration of material degradation, while bone formation was found not to be influenced. Further optimization of the composite material is necessary to increase control over degradation and tissue ingrowth. To cite this article :
van de Watering FCJ, van den Beucken JJJP, Walboomers XF, Jansen JA. Calcium phosphate/poly(d ,l ‐lactic‐co‐glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical‐sized cranial defect.
Clin. Oral Impl. Res. 23 , 2012; 151–159.
doi: 10.1111/j.1600‐0501.2011.02218.x     

泊洛沙姆188-PLGA纳米给药系统对抗耐药肿瘤的研究

目的 利用泊洛沙姆188对PLGA进行化学修饰,制备包载阿霉素的纳米粒,并评价纳米粒在人耐药乳腺癌细胞中的摄取能力及毒性。方法 通过EDC/NHS法合成泊洛沙姆188-PLGA,通过核磁共振对其结构进行表征并测定临界胶束浓度;通过纳米沉淀法制备包载阿霉素的纳米粒,通过粒度仪对纳米粒的粒径及分布进行分析,通过细胞摄取实验及细胞毒性实验对纳米粒的摄取效果及毒性进行评价。结果 成功合成了泊洛沙姆188-PLGA,并制备了粒径在140 nm左右的纳米粒,该纳米粒在人耐药乳腺癌细胞中有较好的摄取效果及较强的毒性。结论 泊洛沙姆188能够逆转耐药,增强耐药细胞对化疗药物的敏感程度。     

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.     

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.