Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study

Abstract

Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

Enhanced oral bioavailability of fluvastatin by using nanosuspensions containing cyclodextrin

“…These include nanostructured lipid carriers, 6 solid dispersion, 7 nanoparticles, 8 , 9 and microspheres. 10 In the past few years, the use of particle size reduction method to form stable nanoparticles has proved an effective strategy to solve this thorny problem. Nanoscale suspensions can be defined as liquid dispersions consisting of solid drug nanoparticles, which are stabilized by polymers and/or surfactants.…”

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket

“…This DDS has been shown to release fluvastatin at a constant rate for >1 month. 35,36 The method of fabricating microcarriers in this study is referenced in these preceding studies with a modification in the impregnation procedure of drugs into PLGA. This is because fluvastatin is water soluble, but BD is water insoluble.…”

Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats

“…A previous study reported that there is evidence to suggest that statins, which have been safely used for treatment of hypercholesterolemia, enhance the biosynthesis of BMP-2 [ 42 ]. Other studies have reported the positive effects of statins on osteogenesis around implants and in tooth extraction sockets [ 23 , 24 ].…”

“…Previous studies reported that the systemic administration of simvastatin promoted bone formation around implants [ 21 ] and a topical application of fluvastatin led to bone formation around tibial titanium implants [ 22 ]. In addition, the injection of poly(lactic-co-glycolic) acid PLGA-fluvastatin microspheres promoted both bone formation and gingival soft tissue healing [ 23 , 24 ]. Jinno et al reported that atelo-collagen and alpha-tricalcium phosphate (α-TCP) as a carrier successfully promoted vertical bone formation on the parietal region [ 25 ].…”