Simvastatin Nanoparticles Research Articles

The Durability of Simvastatin Nanoparticle Coatings on Dental Implant Healing-Abutments

Background: Considering the success of dental implant treatments and their long-term effectiveness, it is important to prevent a series of biological complications such as peri-implant diseases. The development of antimicrobial coatings is known as a promising strategy to overcome these challenges. This study aimed to investigate the durability of simvastatin-loaded gelatin nanoparticle coating on titanium healing abutments. Methods: 40 titanium healing abutments were prepared in two groups, including the test group (titanium healing abutments coated with simvastatin nanoparticles, n=20) and the control group (titanium healing abutments without simvastatin nanoparticle coating, n=20). The dip-coating process was then applied to cover the surface of the healing-abutments. The morphology and composition of coatings were evaluated by Scanning Electron Microscope (SEM) and X-Ray Diffraction analysis (XRD), respectively. Results: The resulting data from SEM and XRD confirmed the successful coating of simvastatin- loaded gelatin nanoparticles on the implant. Based on the Sidak test results, it was observed that the average weight before coating and immediately after coating had a significant difference. Also, the average weight between the initial time (after coating) and the time of 1 day after coating and 30 days after coating was not statistically significant. It means that the coating has been stable for at least 30 days. The difference between the initial weight (after coating) and 60 days after plating was significant. This means that the durability of the coating has decreased until the 60th day. Conclusion: The resulting data showed that the coating of gelatinous nanoparticles containing simvastatin on the titanium healing abutments was successful, and the durability of the coating lasted for at least 1 month.

The influence of Simvastatin carried by Chitosan nanoparticle on bone regeneration using Masson’s Trichrome histochemical stain

Background: Due to the complicated and time-consuming physiological procedure of bone healing, certain graft materials have been frequently used to enhance the reconstruction of the normal bone architecture. However, owing to the limitations of these graft materials, some pharmaceutical alternatives are considered instead. Chitosan is a biopolymer with many distinguishing characteristics that make it one of the best materials to be used as a drug delivery system for simvastatin. Simvastatin is a cholesterol lowering drug, and an influencer in bone formation process, because it stimulates osteoblasts differentiation, bone morphogenic protein 2, and vascular endothelial growth factor. Objectives: histological, histochemical and histomorphometrical analyses were carried out to evaluate the effect of local application of chitosan simvastatin nanoparticles (ChSimN) on bone healing. Materials and Methods: New Zealand rabbits (n=14) were used in this study. Two defects were made: one on the right side (the experimental side) that received ChSimN and the other one on the left side (the control side), which left to heal spontaneously. Seven rabbits were sacrificed after 2 weeks of the experiments, while the others after 4 weeks. Bone samples were taken for histological and histomorphometric study after the sacrifice. Results: The histological study, using both H&E and Masson’s Trichrome stain, revealed that the ChSimN group recorded an increased amount of bone formation at both time points. Histomorphometrical analysis recorded a significant increment in bone marrow and trabecular areas in the ChSimN group. Conclusion: ChSimN had a pronounced effect on bone formation.

Formulation and Evaluation of Simvastatin Nanoparticles

Present study was aimed to formulation and evaluation of Simvastatin nanoparticles. Simvastatin nanoparticles were prepared by High pressure homogenization method by using lipid (Glyceryl Monostearate), polymer (Chitosan, Sodium Alginate) and surfactant (Tween 80) in the formulation. The prepared nanoparticles were evaluated for particle size, zetapotential, entrapment efficiency, drug excipients compatability studies by FTIR, scanning electron microscopy and invitro release studies. Among all the formulations, The formulation F8 showed particle size 97.47nm, PDI as 0.333, zeta potential -30.60mV and % Entrapment efficiency 85.69%, FTIR studies shown that drug was compatable with excipients, Scanning electron microscopy results shown that particles in the formulation shows moderately spherical in shape and drug release maximum 97.28%. So, formulations F8 showed better sustain the drug release for 12hrs period of time as compared to other prepared formulations, hence drug release kinetics was applied for F8 formulation. Drug release kinetic studies it showed that optimized formulation F8 showed zero order with non-fickian mechanism.

Chitosan Nanoparticle/Simvastatin for Experimental Maxillary Bony Defect Healing: A Histological and Histomorphometrical Study.

Biomaterials such as chitosan and simvastatin (Sim) have been introduced to accelerate the extensive and multicellular biological process of bone healing. The aim of this study was to evaluate the bone healing potential of chitosan and Sim, alone or combined. Forty-two male New Zealand rabbits were divided into three groups: chitosan nanoparticles (ChN), Sim and chitosan simvastatin nanoparticles (ChSimN). Two bony defects were created in the maxillary bone. The hole on the right side received one of the experimental materials, while the other side was assigned as the control and left to heal without any intervention. Bone specimens were collected at 2 and 4 weeks and then taken for histological and histomorphometrical analyses. The histological findings revealed that ChN possessed the highest number of osteoblasts and osteoclasts at weeks 2 and osteocytes after 4 weeks. There was a significant difference between the two healing periods regarding all bone parameters across all groups. ChN stood out as the only group that had a significant difference in the count of all bone cells between the two periods, thus having the best potential in promoting bone healing.

Simvastatin Nanoparticles Loaded Polymeric Film as a Potential Strategy for Diabetic Wound Healing: In Vitro and In Vivo Evaluation.

The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds. The aim of the present study is to fabricate nanofilm embedded with simvastatin-loaded chitosan nanoparticles (CS-SIM-NPs) and to explore the efficacy of SIM in diabetic wound healing. The NPs, prepared via ionic gelation, were 173 nm ± 2.645 in size with a zeta potential of -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into the polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats. The results showed a significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site. Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.

Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis.

In this study, an emulsion solvent evaporation method was used to produce Eudragit RL (ERL) nanoparticles (NPs) loaded with simvastatin (SIM) for the treatment of ulcerative colitis (UC). Accordingly, the effects of different formulation variables on the properties of NPs were evaluated using the Box-Behnken design. The optimized NPs were then coated by Eudragit FS30D (EFS30D). Drug release was studied in different physiological environments. Colitis was induced by 3% of acetic acid in rats, which received NPs of SIM (10mg/kg/day), mesalazine (150mg/kg/day), blank NPs and normal saline orally for 5days. Macroscopic histopathological evaluation and biochemical analysis, including myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the colon tissues, were carried out in this study. The optimized SIM-ERL NPs showed the particle size of 182.48 ± 4.57nm, the polydispersity index of 0.29 ± 0.12, the zeta potential of 26.45 ± 4.57mV, drug loading % of 34.64 ± 0.48, the encapsulation efficiency % of 98.68 ± 0.69, and the release efficiency % of 35.78 ± 1.37. Coating the optimized NPs with EFS30D caused an increase in particle size and a decrease in the zeta potential of NPs. The optimized SIM-EFS30D/RL NPs improved the macroscopic and histopathological scores. Also, MPO activity and MDA level were reduced significantly by NPs, as compared to the control group. Therefore, this drug delivery system can be an alternative to the previous treatments of UC.

Dry Powder Formulation of Simvastatin Nanoparticles for Potential Application in Pulmonary Arterial Hypertension.

It has been hypothesized that simvastatin could be used to treat pulmonary arterial hypertension (PAH). This study is intended to formulate a simvastatin nanoparticle dry powder inhalation (DPI) formulation. Simvastatin nanoparticles were prepared via an emulsification and homogenization-extrusion method, followed by spray drying of the colloidal suspension of simvastatin nanoparticles containing mannitol to get it into a respirable size. Particle size distribution, morphology, and crystallinity of the fabricated nanoparticles of the obtained microparticles for DPI formulation were assessed by dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction pattern (XRPD), respectively. Aerosolization performance of the DPI formulation was assessed by the Next Generation Impactor (NGI) equipped with an Aerolizer®. Simvastatin nanoparticles were around 100 nm with a very narrow size distribution (PDI = 0.105). The X-ray diffraction pattern revealed that the crystallinity of simvastatin was decreased by the spray drying procedure. Microscopic images displayed that gathered nanoparticles were in the suitable inhalable range and had the appropriate shape and surface properties for pulmonary delivery. Aerosolization assessment by the NGI indicated a suitable inhalation performance (fine particle fraction of 20%). In conclusion, the results confirmed that the spray drying technique for simvastatin can be optimized to obtain simvastatin aggregated nanoparticles without any coarse carrier to be used in DPI formulation for better deposition of the drug in the lungs for local treatment of PAH.

Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study

Uterine leiomyomas are complex tumours with limited medical treatment options. Simvastatin is used to treat hypercholesterolaemia and has shown promising effects as a treatment option for leiomyomas. Previously, our group demonstrated a promising effect of simvastatin treatment in a patient-derived xenograft mouse model. Here, we tested the efficacy of simvastatin liposomal nanoparticles (NPs). After bilateral leiomyoma xenograft implantation, mice (N = 12) were divided into three treatment arms: control, simvastatin and simvastatin-loaded liposome NPs (simvastatin-NPs). Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP; however, the results were not significant. Due to low bioavailability and short half-life of simvastatin, liposomal NPs have the potential to enhance drug delivery, however, in this study NP did not provide improvement over simvastatin, but did demonstrate their potential for the delivery of simvastatin. Impact statement What is already known on this subject? Simvastatin treatment in a patient-derived xenograft mouse model reduced tumour growth and decreased proliferation. What do the results of this study add? Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP, however, it did not improve the efficacy of simvastatin at reducing tumour growth and proliferation. What are the implications of these findings for clinical practice and/or further research? More studies are needed to optimise the formulation of NPs to further enhance the sustainable delivery of simvastatin.

Evaluation of the efficiency of simvastatin loaded PLGA nanoparticles against acute paraquat-intoxicated rats

Here, we reported a novel nanotherapeutic platform for paraquat (PQ)-induced acute lung injury in animal models using simvastatin (SV) loaded into Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). In this way, Male Wistar rats orally received PQ (120 mg / kg) plus saline, SV (20 mg / kg) or PLGA–SV NPs containing 5, 10 and 20 mg SV/ kg. The levels of TNFα, IL-1β, IL-6 and glutathione content were evaluated. In addition, the pathological changes in the lung were monitored. Our results indicated that PQ (120 mg/kg) significantly reduced the body weight of rats compared to the control group. The most decrease in the level of inflammatory cytokines, bleeding, alveolar destruction as well as lymphocytic infiltration in the lung was observed at group treated with PLGA-SV NPs (10 mg). Free SV (20 mg) as well as PLGA-SV NPs (5 mg) modulated the inflammatory factors and glutathione content, however, they could not prevent tissue damage of PQ. Interestingly, PLGA-SV NPs (20 mg) could not improve the PQ- induced pulmonary damage. In conclusion, PLGA-SV NPs (10 mg) attenuated PQ-induced lung injury. The underlying mechanism may be relevant to increasing glutathione levels and inhibition of the production of inflammatory factors.

Evaluation of Antitumor Efficacy of Chitosan-Tamarind Gum Polysaccharide Polyelectrolyte Complex Stabilized Nanoparticles of Simvastatin.

PurposeThe present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines.Materials and MethodsThe antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles.ResultsFormulated nanoparticles showed high entrapment efficiency (67.19±0.42–83.36±0.23%) and small size (53.3–383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker–Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies.ConclusionThe present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems.

Simvastatin nanosuspensions prepared using a combination of pH-sensitive and timed-release approaches for potential treatment of colorectal cancer

A dual pH- and time-dependent polymeric coated capsule was developed to achieve the site specificity of simvastatin (SIM) release in the colon. To improve the SIM solubility, soluplus-based nanosuspension of the drug were prepared by applying the anti-solvent crystallization technique; this was then followed by lyophilization. Particle size, polydispersity index, and saturation solubility were evaluated. The optimized nanosuspension was combined with SLS and freeze-dried before filling into hard gelatin capsules. Drug release characteristics of the coated capsules were studied in HCl 0.1 N, the phosphate buffers 6.8 and 7.4, and the simulated colonic fluid (pH 6.8). The in-vitro cytotoxic effects of SIM nanoparticles against HT29 cells were then evaluated using the MTT assay. The prepared nanoparticles were spherical with a mean size of 261.66 nm, the zeta potential of −18.20 and the dissolution efficiency of 59.71%. X-ray diffraction and differential scanning calorimetry studies showed that the nanosizing technique transformed the crystalline drug into the more soluble amorphous form. The coated capsules had no release in the gastric media, providing the specific delivery of SIM in the colon. The cytotoxic effect of the SIM nanoparticles was significantly increased, as compared to the free SIM. The findings, therefore, showed that the coated capsules using the two polymers of ethyl cellulose and Eudragit S100 could be suitable for the colon target delivery of SIM.

Development and Bioavailability assessment of simvastatin nanoparticle formulation

Aim: The aim of the present study is to prepare and evaluate nanoparticles containing Simvastatin using chitosan as the polymer. Methods: The Simvastatin loaded nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. Nanoparticles of different core: coat ratio were formulated and evaluated for process yield, loading efficiency, particle size, zeta potential, in vitro drug release, kinetic studies and stability studies. Results: The prepared nanoparticles were white, free flowing and spherical in shape. The infrared spectra showed stable character of Simvastatin in the drug-loaded nanoparticles and revealed the absence of drug polymer interactions. The chitosan nanoparticles have a particle diameter ranging approximately 132.1±5.60 to 774.8±2.60nm and a zeta potential 11.93 to 43.23mV. The formulation with the initial Simvastatin concentration of 0.5 mg/ml provided the highest loading capacity. The in vitro release behavior from all the drug loaded batches were found to follow zero order and provided sustained release over a period of 10 h. No appreciable difference was observed in the extent of degradation of product during 90 days in which nanoparticles were stored at various temperatures. Conclusion: The best-fit release kinetics was achieved with zero order mechanism. The release of Simvastatin was influenced by the drug to polymer ratio and particle size. These results indicate that Simvastatin nanoparticles could be effective in sustaining drug release for a prolonged period.

In Situ Gel Loaded with Chitosan-Coated Simvastatin Nanoparticles: Promising Delivery for Effective Anti-Proliferative Activity against Tongue Carcinoma.

The goal of this study is to develop optimized chitosan-coated Simvastatin (SIM) nanoparticles (NPs) loaded in an in situ gel (ISG) formulation via a face-centered central composite design (FCCCD). Coated SIM-NPs were doped with Quercetin (QRC) using a modified nanoprecipitation method. The concentrations of poloxamer 188 (A) and chitosan (B) at five different levels, plus/minus alpha (+1.414 and −1.414: axial points), plus/minus 1 (factorial points) and the center point were optimized for particle size (PS-Y1), entrapment efficacy (EE-Y2) and stability index (SI-Y3). Based on the desirability approach, a formulation containing poloxamer 188 0.24% and chitosan 0.43% renders the prerequisites of optimum formulation for preparing SIM–QRC NP-loaded ISG. Scanning microscopy showed spherical SIM-NPs, indicating monodispersity in the range of 0.50 ± 0.04 nm with a charge of +32.42 mV. The optimized formulation indicated the highest EE 79.67% and better stability at 4 °C. Drug release from SIM–QRC NP-loaded ISG was slower to plateau by up to 96 h and, at the end of 168 h, only 65.12% of SIM was released in a more controlled manner in comparison to SIM–QRC NPs and plain SIM. ISG formulation showed a considerable increase in apoptosis occurrence through caspase-3 mediation and it also enhanced the tumor suppressor protein levels. Enhanced biological activity of SIM was observed due to QRC enabling promising drug and polymer synergistic interaction. The proposed formulation can provide a breakthrough in localized therapy, overcoming the potential drawbacks of systemic chemotherapy for tongue carcinoma.

Simvastatin preparations promote PDGF-BB secretion to repair LPS-induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway.

Endothelial barrier dysfunction is a critical pathophysiological process of sepsis. Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction. Statins may have a protective effect on endothelial barrier function. However, the effect and mechanism of statins on lipopolysaccharide (LPS)‐induced endothelial barrier dysfunction remain unclear. Simvastatin (SV) was loaded in nanostructured lipid carriers to produce SV nanoparticles (SV‐NPs). Normal SV and SV‐NPs were used to treat human umbilical vein vascular endothelial cells (HUVECs) injured by LPS. Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay. LY294002 and imatinib were used to inhibit the activity of PI3K/Akt and platelet‐derived growth factor receptor (PDGFR) β. IQ‐GTPase‐activating protein 1 (IQGAP1) siRNA was used to knockdown endogenous IQGAP1, which was used to verify the role of the PDGFRβ/PI3K/Akt/IQGAP1 pathway in SV/SV‐NPs‐mediated barrier protection in HUVECs injured by LPS. The results show that SV/SV‐NPs promoted the migration and decreased the permeability of HUVECs treated with LPS, and the efficacy of the SV‐NPs exceeded that of SV significantly. LY294002, imatinib and IQGAP1 siRNA all suppressed the barrier protection of SV/SV‐NPs. SV/SV‐NPs promoted the secretion of platelet‐derived growth factor‐BB (PDGF‐BB) and activated the PDGFRβ/PI3K/Akt/IQGAP1 pathway. SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRβ/PI3K/Akt/IQGAP1 pathway and PDGF‐BB secretion. As an appropriate formulation for restoring endothelial dysfunction, SV‐NPs may be more effective than SV.

Simvastatin Nanoparticles Reduce Inflammation in LPS-Stimulated Alveolar Macrophages

Simvastatin (SV) is widely used as a lipid-lowering medication that has also been found to have beneficial immunomodulatory effects for treatment of chronic lung diseases. Although its anti-inflammatory activity has been investigated, its underlying mechanisms have not yet been clearly elucidated. In this study, the anti-inflammatory and antioxidant effects and mechanism of simvastatin nanoparticles (SV-NPs) on lipopolysaccharide-stimulated alveolar macrophages (AMs) NR8383 cells were investigated. Quantitative cellular uptake of SV-NPs, the production of inflammatory mediators (interleukin-6, tumor necrosis factor, and monocyte chemoattractant protein-1), and oxidative stress (nitric oxide) were tested. Furthermore, the involvement of the nuclear factor κB (NF-κB) signaling pathway in activation of inflammation in AMs and the efficacy of SV were visualized using immunofluorescence. Results indicated that SV-NPs exhibit a potent inhibitory effect on nitric oxide production and secretion of inflammatory cytokine in inflamed AM, without affecting cell viability. The enhanced anti-inflammatory activity of SV-NPs is likely due to SV-improved chemical-physical stability and higher cellular uptake into AM. The study also indicates that SV targets the inflammatory and oxidative response of AM, through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of SV for treatment of chronic inflammatory lung diseases.

Locally Applied Simvastatin as an Adjunct to Promote Spinal Fusion in Rats.

Basic Science. To determine if locally delivered simvastatin can enhance bone formation in a rat spinal fusion model. The bone-anabolic properties of statins in fracture healing are well established, however, few studies have evaluated the impact of locally delivered statins in spinal fusion. We formulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles by adapting previously published techniques. Two types of nanoparticles were created: simvastatin nanoparticles (SimNP) and nanoparticles without simvastatin (BlankNP). Drug elution from SimNP was characterized. Osteoblastic differentiation was analyzed using MC3T3-E1 cells cultured in differentiation medium containing SimNP or BlankNP. Forty male 12 week old outbred Wistar rats underwent uninstrumented posterolateral fusion using iliac crest bone graft and BlankNP, SimNP or simvastatin drug. X-rays to assess bone formation were obtained at 4 weeks and 9 weeks post-operatively. Spines were explanted at 9 weeks for micro-CT analysis, and a blinded manual assessment of fusion (MAF). SimNP achieved a release efficiency of 74.1% with ∼50% release occurring in the first day. Simvastatin and SimNP treated cells showed significantly greater expression of osteopontin (OPN) and osteocalcin (OCN). On micro-CT analysis, SimNP animals had higher bone volume and percent bone volume (bone volume/total volume) than control animals. SimNP rats had higher X-ray scores at 4 weeks (p=0.010) and 9 weeks (p<0.001) relative to BlankNP. MAF showed that SimNP had a higher fusion rate than BlankNP (42.9% vs. 0%, p=0.006). We were able to validate that sustained release of simvastatin via a PLGA nanoparticle. SimNP was able to induce an increase in mineralization as well as an increase in markers of bone formation. X-ray analysis, micro-CT quantification, and MAF assessment of SimNP treated rats showed significantly greater bone formation and fusion mass strength relative to vehicle treated animals. Simvastatin may be a safe, cost-effective bone anabolic agent for use in spinal fusion. N/A.

Combination of a Bioceramic Scaffold and Simvastatin Nanoparticles as a Synthetic Alternative to Autologous Bone Grafting.

The fragile nature of porous bioceramic substitutes cannot match the toughness of bone, which limits the use of these materials in clinical load-bearing applications. Statins can enhance bone healing, but it could show rhabdomyolysis/inflammatory response after overdosing. In this study, the drug-containing bone grafts were developed from poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles encapsulating simvastatin (SIM) (SIM-PP NPs) loaded within an appropriately mechanical bioceramic scaffold (BC). The combination bone graft provides dual functions of osteoconduction and osteoinduction. The mechanical properties of the bioceramic are enhanced mainly based on the admixture of a combustible reverse-negative thermoresponsive hydrogel (poly(N-isopropylacrylamide base). We showed that SIM-PP NPs can increase the activity of alkaline phosphatase and osteogenic differentiation of bone marrow stem cells. To verify the bone-healing efficacy of this drug-containing bone grafts, a nonunion radial endochondral ossification bone defect rabbit model (N = 3/group) and a nonunion calvarial intramembranous defect Sprague Dawley (SD) rat model (N = 5/group) were used. The results indicated that SIM-PP NPs combined with BC can improve the healing of nonunion bone defects of the radial bone and calvarial bone. Therefore, the BC containing SIM-PP NPs may be appropriate for clinical use as a synthetic alternative to autologous bone grafting that can overcome the problem of determining the clinical dosage of simvastatin drugs to promote bone healing.

Inhaled Simvastatin Nanoparticles for Inflammatory Lung Disease

Current inhaled treatments are not adequate to treat all lung diseases. In this study, a promising nanotechnology has been developed to deliver a potential anti-inflammatory and muco-inhibitory compound, simvastatin, for treatment of inflammatory lung diseases via inhalation. Simvastatin nanoparticles (SV-NPs) encapsulated with poly(lactic-co-glycolic) acid were fabricated using the solvent and anti-solvent precipitation method. SV-NPs were found to be stable up to 9months at 4°C in a freeze-dried form prior to reconstitution. The amount of mucus produced was significantly reduced after SV-NPs treatment on inflammation epithelial cell models and were effective in suppressing the proinflammatory marker expression. This study suggests that SV-NPs nebulization could potentially be used for the treatment of chronic pulmonary diseases.

Simvastatin nanoparticles attenuated intestinal ischemia/reperfusion injury by downregulating BMP4/COX-2 pathway in rats.

The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.

Corrigendum: Preparation, optimization, and characterization of simvastatin nanoparticles by electrospraying: An artificial neural networks study

Article First Published Online: 5 August 2016 DOI: 10.1002/app.44205 [Article in J. Appl. Polym. Sci. 2016, 133, DOI: 10.1002/app.43602] In the published article cited above, Figure 4C was reproduced incorrectly. The correct figure is given below. Please also note that OH stretching vibrations are not present at 3200–3500 cm−1 in the FTIR spectrum of PLGA, as stated in the text. The authors regret any inconvenience this may have caused. FT-IR spectra of SIM (A), PLGA (B), and SIM-loaded PLGA NPs.