Lovastatin Nanoparticle Synthesis and Characterization for Better Drug Delivery
TL;DR: Nano drug delivery system is the latest technology employed in various medicinal applications and NLCs are a smarter generation of drug delivery carriers for lovastatin, a important drug which arrests the rate-limiting step of the cholesterol cascade.
Abstract: Nano drug delivery system is the latest technology employed in various medicinal applications. This technol- ogy can be adapted to the conventional drug administration due to its site-specific targeting phenomena. The oral lipo- philic drug administration has its drawbacks due to poor solubility and bioavailability. Lipid-based carrier systems are now widely popular due to improved efficiency, especially for lovastatin delivery. Lovastatin is an important drug which arrests the rate-limiting step of the cholesterol cascade. This drug has short half-lives, poor oral-administered bioavailabil- ity, poor solubility, and is rapidly metabolizable. Based on the composition, the drug delivery carriers are classified into solid lipid nanoparticles (SLNs), lipid emulsions (LEs), and nanostructured lipid carriers (NLCs). Among them, NLCs are a smarter generation of drug delivery carriers for lovastatin. The selection of various lipid systems and their formulation are discussed in this paper. Moreover, the characterization of these carrier systems to achieve the optimal characteristic features is discussed in a concise manner.
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TL;DR: Zerumbone-loaded nanostructured lipid carriers (ZER-NLC) have potential as a sustained-release drug carrier system for the treatment of leukemia, according to physicochemical properties.
Abstract: Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostructured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68 ± 0.1 nm and a polydispersity index of 0.29 ± 0.004 μm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was −25.03 ± 1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64 ± 0.38 μg/mL, and for free zerumbone was 5.39 ± 0.43 μg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia.
116 citations
Cites background from "Lovastatin Nanoparticle Synthesis a..."
...Approximately 40% of drugs in the pipeline and 70% of synthetic therapeutic molecules are plagued with poor solubility, oral bioavailability, and delivery.(8,9) Drugs with poor solubility suffer from limited transport after oral administration because of a low concentration gradient between the gut and blood vessels....
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TL;DR: Crystals obtained from nitromethane solutions were found to have a very large reduction in aspect ratio to a prismatic morphology reflecting this solvent's propensity to interact with hydrophobic surfaces, critically with no polymorph change.
27 citations
TL;DR: The importance and role of various nanoparticulate systems as carrier for antihyperlipidemic drugs in the treatment of hyperlipidemia and the development of efficient delivery methods and carriers are focused on.
Abstract: Hyperlipidemia is a prevailing risk factor that leads to development and progression of atherosclerosis and consequently cardiovascular diseases. Several antihyperlipidemic drugs are having various disadvantages such as low water solubility and poor bioavailabilty due to presystemic gastrointestinal clearance. Thus, there is a considerable need for the development of efficient delivery methods and carriers. This review focuses on the importance and role of various nanoparticulate systems as carrier for antihyperlipidemic drugs in the treatment of hyperlipidemia. Some nanoparticle technology-based products are approved by FDA for effective treatment of hyperlipidemia, namely Tricor® by Abbott Laboratories (Chicago, IL, USA) and Triglide® by Skye Pharma (London, UK). Efforts to address each of these issues are going on, and should remain the focus on the future studies and look forward to many more clinical products in the future.
26 citations
Cites background from "Lovastatin Nanoparticle Synthesis a..."
...The nano-aided drug delivery system is a suitable choice for poorly soluble lipophilic drugs (Seenivasan et al., 2011)....
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TL;DR: In vivo pharmacodynamics studies showed that the optimized LOV-s-rHDL displayed the most pronounced anti-atherosclerotic effect on decreasing plaque area and reducing the MMP level following an 8-week dosing regimen.
Abstract: Reconstituted high density lipoprotein (rHDL) is a biomimetic nanoparticle with plaque targeting and anti-atherosclerotic efficacy. In this work, we report on a strategy to rational design of lovastatin (LOV)-loaded spherical rHDL (LOV-s-rHDL) for efficient and safe anti-atherosclerotic therapy. Briefly, three LOV-s-rHDLs were formulated with LOV/s-rHDL at ratios of 8:1, 10:1, and 15:1 upon their respective median-effect values (Dm). The combined inhibitory effect between LOV and s-rHDL of different LOV-s-rHDL formulations on DiI-labeled oxLDL internalization was systemically investigated in RAW 264.7 cells based on the median-effect principle. Median-effect analysis demonstrated that the optimized LOV-s-rHDL was formulated with a ratio of 10:1 (Dm LOV:Dm s-rHDL), in which LOV and s-rHDL carrier showed the best synergistic effect, presumably ascribed to their inhibitory effect on CD36 and SR-A expression according to the Western blot analysis. In vivo pharmacodynamics studies showed that the optimized LOV...
18 citations
TL;DR: Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension, and the SSL-S provided superior drug solubilization under simulated intestinal digesting condition.
Abstract: Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.
10 citations
References
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19 Dec 2012TL;DR: The emerging formulation designs for delivering of poorly water-soluble drugs, including the massive use of surface-active excipients for solubilisation, are addressed.
Abstract: The drug candidates coming from combinatorial chemistry research and/or the drugs selected from biologically based high-throughput screening are quite often very lipophilic, as these drug candidates exert their pharmacological action at or in biological membranes or membrane-associated proteins. This challenges drug delivery institutions in industry or academia to develop carrier systems for the optimal oral and parenteral administration of these drugs. To mention only a few of the challenges for this class of drugs: their oral bioavailability is poor and highly variable, and carrier development for parenteral administration is faced with problems, including the massive use of surface-active excipients for solubilisation. Formulation specialists are confronted with an even higher level of difficulties when these drugs have to be delivered site specifically. This article addresses the emerging formulation designs for delivering of poorly water-soluble drugs.
489 citations
TL;DR: The present review discusses the potential use of solid lipid nanoparticles for brain drug targeting purposes and the state of the art on surfactant-coated poly(alkylcyanoacrylate) nanoparticles specifically designed for brain targeting is given by emphasizing the transfer of this technology to solid lipid matrices.
373 citations
"Lovastatin Nanoparticle Synthesis a..." refers background in this paper
...Examples of this delivery system were successfully employed in the field of brain, cosmetic, dermal, bone fracture, and cancer target delivery [2-5]....
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...Keywords: Lovastatin, nanoparticles, solid lipid nanoparticles, lipid emulsions, nano-structured lipid carriers....
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...These systems demand suitable conditions for drug delivery, viz., the use of physiologically tolerated lipids, large-scale production, protection of drugs from degradation, improved bioavailability, minimum level of toxicity, and controlledrelease characteristics....
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TL;DR: In vitro release kinetics demonstrated that lovastatin release could be reduced by up to 60% with lipid nanoparticles containing Myverol as the lipophilic emulsifier, which showed a decreasing order of NLCs>LEs>SLNs.
251 citations
"Lovastatin Nanoparticle Synthesis a..." refers background in this paper
...These systems demand suitable conditions for drug delivery, viz., the use of physiologically tolerated lipids, large-scale production, protection of drugs from degradation, improved bioavailability, minimum level of toxicity, and controlledrelease characteristics....
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...This paper discusses emerging formulation designs for the delivery of poorly water-soluble lovastatin, their characterization, and applications....
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...Carrier development for the parenteral administration of these drugs has many problems including the massive use of surface-active excipients for solubilization [1]....
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...Keywords: Lovastatin, nanoparticles, solid lipid nanoparticles, lipid emulsions, nano-structured lipid carriers....
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...However, the oral administration of this drug has certain limitations, viz., poor bioavailability, nonhepatic shunting, side effects due to higher dosage, more excretion in bile....
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TL;DR: In vitro stability studies showed the slow release and stability of lovastatin SLN, and the relative bioavailabilities of lovaston hydroxy acid of SLN were increased by ∼173% and 324%, respectively, compared with the reference Lovastatin suspension.
Abstract: The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wistar rats after intraduodenal administration of lovastatin suspension and SLN. Stable lovastatin SLN having a mean size range of 60 to 119 nm and a zeta potential range of −16 to −21 mV were developed. More than 99% of the lovastatin was entrapped in the SLN. Lovastatin was dispersed in an amorphous state, and triglycerides were in {ieE162-1} form in the SLN. In vitro stability studies showed the slow release and stability of lovastatin SLN. The relative bioavailabilities of lovastatin and lovastatin hydroxy acid of SLN were increased by ∼173% and 324%, respectively, compared with the reference lovastatin suspension.
134 citations
"Lovastatin Nanoparticle Synthesis a..." refers background in this paper
...However, the oral administration of this drug has certain limitations, viz., poor bioavailability, nonhepatic shunting, side effects due to higher dosage, more excretion in bile....
[...]
...Carrier development for the parenteral administration of these drugs has many problems including the massive use of surface-active excipients for solubilization [1]....
[...]
...These systems demand suitable conditions for drug delivery, viz., the use of physiologically tolerated lipids, large-scale production, protection of drugs from degradation, improved bioavailability, minimum level of toxicity, and controlledrelease characteristics....
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TL;DR: Preclinical results suggest that lovastatin administered in a nanobead preparation may be therapeutically useful in hastening repair of human fractures.
93 citations