Glimepiride Loaded Poly(D,L-lactide-co-glycolide) Microspheres Improve Osseointegration of Dental Implants in Type 2 Diabetic Rats

The patients with type 2 diabetes mellitus (T2DM) have high dental implant failure frequency. This study explores the function of glimepiride local delivery on dental implant osseointegration in diabetes animal. Glimepiride loaded PLGA microspheres were loaded on the surface of the dental implant, and transplanted into ten Goto-Kakizaki (GK) rats. Blood sugar level and Implant Stability Quotient (ISQ) were measured every week after surgery. Histological, osseointegration rate and bone-implant contact (BIC) rate analysis were performed to evaluate dental osseointegration. The results showed that Glimepiride loaded Poly-lactide-co-glycolide (PLGA) microspheres have sustained-release curve. The glimepiride group exhibited greater ISQ than the control group. The BIC rate of the control and glimepiride group was 44.60%±1.95% and 59.80%±1.79%, respectively. This study demonstrated that the glimepiride group has a significantly greater osseointegration rate than that of the control group. Thus, Glimepiride could provide an alternative drug release microspheres for enhance the dental implant osseointegration in diabetes patients.

In vitro drug release and antibacterial activity evaluation of silk fibroin coated vancomycin hydrochloride loaded poly (lactic-co-glycolic acid) (PLGA) sustained release microspheres

Currently, the treatment of osteomyelitis poses a great challenge to clinical orthopedics. The use of biodegradable materials combined with antibiotics provides a completely new option for the treatment of osteomyelitis. In this study, vancomycin hydrochloride (VANCO) loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double emulsion solvent evaporation method, and the in vitro drug release behaviors of the drug loaded microspheres were explored after coating with different concentrations of silk fibroin (SF). Drug loading, encapsulation efficiency, Scanning electron microscopy, particle size analysis, Fourier transform infrared spectroscopy, hydrophilicity, in vitro drug release, and in vitro antibacterial activity were evaluated. The results showed that the drug loading of vancomycin loaded PLGA microspheres was (24.11 ±1.72)%, and the encapsulation efficiency was (48.21 ±3.44)%. The in vitro drug release indicated that the drug loaded microspheres showed an obvious initial burst release, and the drug loaded microspheres coated with SF could alleviate the initial burst release in varying degrees. It also can reduce the amount of cumulative drug release, and the effect of microspheres coated with 0.1% concentration of SF is the best. The time of in vitro drug release in different groups of drug loaded microspheres can be up to 28 days. The microspheres coated with (0.1%SF) or without (0%SF) SF showed a cumulative release of (82.50±3.51)% and (67.70±3.81)%,respectively. Therefore, the surface coating with SF of vancomycin loaded microspheres can alleviate the initial burst release, reduce the cumulative drug release, potentially prolong the drug action time, and improve the anti-infection effect.

Effect of Sizes on the Lung-Targeting and Biocompatibility of Intravenously Administered Biodegradable PLGA Microspheres

Background: In the treatment of lung diseases, drug showed low bioavailability and efficacy by conventional administration methods. Passive lung-targeting microspheres provide a method to deliver drugs from the vascular side, there is still a paucity of systematic studies on the biocompatibility of biodegradable-polymer microspheres. Results: We used poly (lactic acid-glycolic acid) (PLGA) microspheres with different particle sizes (3, 10, 25, and 40 mm) as a model. The optimal lung-targeting particle size of the PLGA microspheres is 10 mm and the corresponding range of maximum tolerated dose is 125-150 mg/kg. We hypothesized that the decrease of blood oxygen saturation under treatment of microspheres was caused by pulmonary embolism. We found varying degrees of blood circulation loss of lungs by micro computed tomography test, which indicated severe pulmonary embolism subsequent to intravenous injection of microspheres with a particle size >25 mm. Furthermore, we found lung injury and microspheres leaked from the blood vessels into the alveoli by H&E staining. This process was likely induced by increased secretion of matrix metalloproteinases (MMPs), which destroyed the alveolar-capillary barrier and trigger an inflammatory cascade. Finally, we found that optimal particle size and dose conditions did not affect normal physiological activities after the microspheres degraded. The upregulation of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) induced vessel recanalization and reestablishment, which promoted the progress of lung repair. Conclusions: Collectively, our results highlight the importance of accurately designing the optimal size and dose of microspheres for passive lung-targeting delivery.