Simvastatin-loaded solid lipid nanoparticles for enhanced anti-hyperlipidemic activity in hyperlipidemia animal model

Rizvi, Syed Zaki Husain; Shah, Fawad Ali; Khan, Namrah; Muhammad, Iftikhar; Ali, Khan Hashim; Ansari, Muhammad Mohsin; Din, Fakhar ud; Qureshi, Omer Salman; Kim, Kyoung-Won; Choe, Yeong-Hwan; Kim, Jin‐Ki; Zeb, Alam

doi:10.1016/j.ijpharm.2019.02.002

Cited by 102 publications

(48 citation statements)

References 51 publications

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“…The experimental domain of the two-level D-optimal screening experimental design of the formulation parameters for the 46 runs and their measured responses are summarized in Table S1 of the Supplementary Materials. The observed response coefficients of the experimental runs along with the Analysis of Variance (ANOVA) results calculated for measured responses such as the p-value are summarized in Table 2 and Equations ( 3)- (5). Statistical analysis using ANOVA revealed that the sequential model suggested for evaluating the different parameters was linear.…”

Section: Combined D-optimal Screening Designmentioning

confidence: 99%

“…It is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase competitive inhibitor. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, a ratelimiting step in cholesterol biogenesis [5]. AT bioavailability is approximately 12% and is classified as a class II drug according to the Biopharmaceutical Classification System (BCS) [6].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

et al. 2021

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The aim of the current study is to establish a comprehensive experimental design for the screening and optimization of Atorvastatin-loaded nanostructured lipid carriers (AT-NLCs). Initially, combined D-optimal screening design was applied to find the most significant factors affecting AT-NLCs properties. The studied variables included mixtures of solid and liquid lipids, the solid/liquid lipid ratio, surfactant type and concentration, homogenization speed as well as sonication time. Then, the variables homogenization speed (A), the ratio of solid lipid/liquid lipid (B), and concentration of the surfactant (C) were optimized using a central composite design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were chosen as dependent responses. The optimized AT-NLCs demonstrated a nanometric size (83.80 ± 1.13 nm), Polydispersity Index (0.38 ± 0.02), surface charge (−29.65 ± 0.65 mV), and high drug incorporation (93.1 ± 0.04%). Fourier Transform Infrared Spectroscopy (FTIR) analysis showed no chemical interaction between Atorvastatin and the lipid mixture. Differential Scanning Calorimetry (DSC) analysis of the AT-NLCs suggested the transformation of Atorvastatin crystal into an amorphous state. Administration of the optimized AT-NLCs led to a significant reduction (p < 0.001) in serum levels of rats’ total cholesterol, triglycerides, and low-density lipoproteins. This change was histologically validated by reducing the relevant steatosis of the liver.

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Section: Combined D-optimal Screening Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

et al. 2021

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“…Among these drugs, statins are widely used to retard the atherosclerosis in patients with hyperlipidemia (Macan et al, 2015). In fact, these drugs have also been reported to present anti-inflammatory, anticancer, antioxidant and immunomodulatory effects (Chen et al, 2018;Rizvi et al, 2019). Experiments in vivo and in vitro have shown that statins protect organism damage from oxidative stress by eliminating superoxide anion and hydroxyl radicals (Murakami et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Experiments in vivo and in vitro have shown that statins protect organism damage from oxidative stress by eliminating superoxide anion and hydroxyl radicals (Murakami et al, 2018). Simvastatin (SIM), a family of statins, is the first choice for the treatment of hypercholesterolemia, dyslipidemia, and coronary heart disease (Rizvi et al, 2019). It is an inhibitor of 3-hydroxy-3methylglutaryl CoA reductase (HMG-CoA reductase) and responsible for converting HMG-CoA into mevalonate (Harisa et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

et al. 2020

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The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

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“…Scanning was performed with a 2θ range from 10° to 80° with an increase of 5°/min. 37 …”

Section: Methodsmentioning

confidence: 99%

Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers

Guo¹,

Ali²,

Khan³

et al. 2021

IJN

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Background The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer. Methods HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo. Results The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced ( P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs. Conclusion These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.

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Simvastatin-loaded solid lipid nanoparticles for enhanced anti-hyperlipidemic activity in hyperlipidemia animal model

Cited by 102 publications

References 51 publications

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers

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