Controlled release of lovastatin from poly(lactic-<em>co</em>-glycolic acid) nanoparticles for direct pulp capping in rat teeth

Abstract

Statin at appropriate concentrations has been shown to induce odontoblastic differentiation, dentinogenesis, and angiogenesis. However, using a carrier to control statin release might reduce toxicity and enhance its therapeutic effects. The aim of this study was to prepare poly( d , l -lactide- co -glycolide acid) (PLGA) nanoparticles that contain lovastatin for application in direct pulp capping. The PLGA–lovastatin particle size was determined using dynamic light scattering measurements and transmission electron microscopy. In addition, the release of lovastatin was quantified using a UV–Vis spectrophotometer. The cytotoxicity and alkaline phosphatase (ALP) activity of PLGA–lovastatin nanoparticles on human dental pulp cells were investigated. Moreover, a real-time polymerase chain reaction (PCR) assay, Western blot analysis, and an enzyme-linked immunosorbent assay (ELISA) were used to examine the osteogenesis gene and protein expression of dentin sialophosphoprotein (DSPP), dentin matrix acidic phosphoprotein 1 (DMP1), and osteocalcin (OCN). Finally, PLGA–lovastatin nanoparticles and mineral trioxide aggregate (MTA) were compared as direct pulp capping materials in Wistar rat teeth. The results showed that the median diameter of PLGA–lovastatin nanoparticles was 174.8 nm and the cumulative lovastatin release was 92% at the 44th day. PLGA–lovastatin nanoparticles demonstrated considerably a lower cytotoxicity than free lovastatin at 5, 9, and 13 days of culture. For ALP activity, the ALP amount of PLGA–lovastatin (100 μg/mL) was significantly higher than that of the other groups for 9 and 13 days of culture. The real-time PCR assay, Western blot analysis, and ELISA assay showed that PLGA–lovastatin (100 μg/mL) induced the highest mRNA and protein expression of DSPP, DMP1, and OCN in pulp cells. Histological evaluation of the animal studies revealed that MTA was superior to the PLGA–lovastatin in stimulating the formation of tubular dentin in an observation period of 2 weeks. However, in an observation period of 4 weeks, it was evident that the PLGA–lovastatin and MTA were competitive in the formation of tubular reparative dentin and a complete dentinal bridge.

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage

“…[10][11][12] Thus, there has been great interest in using an effective drug delivery system for statins to improve its efficiency. 13,14 In this regard, the nano-drug delivery system has great promise as it effectively extends the half-life of the drug's cycle and allows for the administration of lower doses and at a lower frequency to minimize toxicity. [15][16][17] Specifically, polymeric nanomicelles that self-assemble from copolymers composed of a hydrophilic shell and a hydrophobic core are good candidates for poorly water-soluble or hydrophobic drugs where the drugs stay in the core and the hydrophilic shell provides a stabilizing interface between the core and the outside aqueous environment.…”

Present status and future directions: Hydraulic materials for endodontic use

“…Further research of capped inflamed pulps is needed to further validate the pulp‐capping potential of calcium silicate cements. In exposed pulps with no pulp‐capping agents or sealed with a sterile piece of Teflon tape, an initial mild‐to‐moderate inflammation was observed (Lin et al, 2017; Trongkij et al, 2019). Considering the fact that sterile Teflon tape is inert, this inflammation may be attributed to the trauma induced by surgical procedures.…”

Studying Effects of Calcium Oxide Nanoparticles on Dentinogenesis in Male Wistar Rats

“…Furthermore, it was stated that nanotechnology facilitates oral administration of different drugs [ 24 , 25 ]. Other nanoparticles containing poly(d,l-lactide-co-glycolide) acid and lovastatin were used as a direct pulp capping and found effective to induce odontoblastic differentiation, dentinogenesis, and angiogenesis at the pulp exposure site in rat teeth [ 26 ]. However, cytotoxicity of statin at high concentrations has been a matter of concern in some studies [ 26 , 27 ].…”

“…Other nanoparticles containing poly(d,l-lactide-co-glycolide) acid and lovastatin were used as a direct pulp capping and found effective to induce odontoblastic differentiation, dentinogenesis, and angiogenesis at the pulp exposure site in rat teeth [ 26 ]. However, cytotoxicity of statin at high concentrations has been a matter of concern in some studies [ 26 , 27 ]. Therefore, the current study was aimed to evaluate the influence of daily administration of CaO-NPs at different dosages (25, 50, and 100 mg/kg) on predentin thickness, periodontal ligament thickness, number of blood vessels, and blood glucose level of Wistar rats over a period of 60 days.…”