固体脂质纳米粒和纳米结构脂质载体在药物传递中的研究进展

基于固体脂质的纳米粒（Solid lipid - based nanoparticles,SLBNs）作为新型药物传递系统比常规的药物传递系统存在优势。通常,基于固体脂质的纳米粒可以分成两种形态,即固体脂质纳米粒（ Solid lipid nanoparticles, SLNs）和纳米结构脂质载体（Nanostructured lipid carriers,NLCs）。但固体脂质纳米粒与纳米结构脂质载体在基质的组成上不同,本文就基于固体脂质的纳米粒的制备技术、表征方法及应用的最新研究进展进行总结,为基于固体脂质的纳米粒进一步研究提供参考依据。     

固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的研究进展

目的介绍固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的应用与优势,为其开发利用提供参考。方法查阅国内外相关文献共30余篇,从固体脂质纳米粒和纳米结构脂质载体用于经皮给药系统的优势、药物在固体脂质纳米粒和纳米结构脂质载体中的分布形式及固体脂质纳米粒和纳米结构脂质载体在经皮给药领域中的应用等方面进行综述。结果固体脂质纳米粒和纳米结构脂质载体可以增强药物稳定性,能在皮肤表面产生包封效应,增加皮肤水合作用,具有药物靶向性。结论固体脂质纳米粒和纳米结构脂质载体是极有发展前景的新型经皮给药系统。     

布地奈德固体脂质纳米粒肺部给药系统的制备和评价(英文)

为改善布地奈德的溶解度和吸收,制备并评价了布地奈德固体脂质纳米粒(BUD-SLNs)。通过计算部分溶解度参数选择了单硬脂酸甘油酯作为脂材。经处方优化采用乳化-超声分散的方法制备的BUD-SLNs,包封率为(97.77±2.60)%;平均粒径是147.3nm,粒径分布均匀(PDI=0.228)。透射电镜下可见圆整颗粒。差热分析和X射线衍射实验的结果表明BUD以分子形式分散在SLNs中,体外释放结果表明BUD-SLNs符合双相动力学方程,属于均相骨架结构。研究结果为BUD-SLNs在肺部给药奠定了基础。     

Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery

Abstract

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199?nm, while the SLNs prepared with palmitic acid had particle size in the range of 126–160?nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations.     

Preparation,characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system

This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(ζ )-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive ζ -potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components.     

Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery

Solid lipid nanoparticles (SLNs) are essentially composed of triglyceride(s) that orient to form a polar core with polar heads oriented toward the aqueous phase, resembling chylomicrons. The composition of such SLNs may alter the course of drug absorption predominantly to and through lymphatic route and regions, presumably following a transcellular path of lipid absorption, especially by enterocytes and polar epithelial cells of the intestine. SLNs were prepared using stearic acid, glycerol monostearate, tristearin, and Compritol 888 ATO by solvent diffusion method using demineralized double-distilled water as the dispersion medium. The SLNs were characterized for shape, size, zeta potential, and percentage drug content and its release. The characterization of SLNs suggests that Compritol 888 ATO–based nanoparticles were heterogeneous with better drug-loading and release characteristics as compared with the other formulations. The selected products were studied for in vivo absorption and hence bioavailability by measure of area under the blood plasma curve plotted as a function of time. Periodic lymphatic concentration of drug following oral administration of respective formulations was also determined by mesenteric duct cannulation and collection of samples. The comparative study conducted on methotrexate (MTX)-bearing SLNs revealed that the formulation based on Compritol 888 ATO could noticeably improve the oral bioavailability of MTX, presumably following SLNs constituting lipid digestion and co-absorption through lymphatic transport and route.     

Solid lipid nanoparticles for ocular drug delivery

Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.     

Solid lipid nanoparticles for parenteral drug delivery

This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticles are introduced and structural differences are pointed out. Different production methods including the suitability for large scale production are described. Stability issues and drug incorporation mechanisms into the particles are discussed. In the second part, the biological activity of parenterally applied SLN and biopharmaceutical aspects such as pharmacokinetic profiles as well as toxicity aspects are reviewed.     

Solid lipid nanoparticles as drug delivery systems

For a decade, trials have been made to utilize solid lipid nanoparticles (SLNs) as alternative drug delivery systems to colloidal drug delivery systems such as lipid emulsions, liposomes, and polymeric nanoparticles. Various lipid matrices, surfactants, and other excipients used in formulation, preparation methods, sterilization and lyophilization of SLNs are discussed in this article. Entrapment efficiency of drug carrier and its effect on physical parameters, drug release, and release mechanisms of various compositions are reviewed and discussed. Important points in characterization and stability of SLNs are outlined. Various in vitro studies carried out by different research groups are mentioned in addition to in vivo evaluation. Exploitation potential of SLNs to administer by various routes of administration are covered. Passive and active drug targeting using SLNs are presented.     

Solid lipid nanoparticles for topical drug delivery

Solid lipid nanoparticles (SLN) have shown interesting potential as a drug delivery system for the topical delivery of various drugs. However, their performance when applied to the skin has not been fully investigated because of the complexity of their composition and structure. Theoretically, drug can be targeted systemically to the vasculature in the dermis, locally to the skin strata, or superficially to the surface of the skin. Therefore, the topical delivery vehicle should be designed according to the desired therapeutic purposes. To understand drug permeation behavior, it is essential to elucidate the pattern of drug release from the SLN formulations. A number of different drug release patterns have been outlined in the literature, and these patterns have been found to be related to the manufacturing process of the vehicle. In this paper, we summarize the results of SLN-mediated skin penetration data in the literature and illustrate several theoretical mechanisms of SLN-skin interactions that might take place at the site of action. Substantial research dedicated to the development of this promising drug delivery system is still required.     

Physicochemical characterization of curcuminoid-loaded solid lipid nanoparticles

Curcuminoid-loaded solid lipid nanoparticles (SLN) were produced by melt-homogenization. The used lipid matrices were medium chain triglycerides, trimyristin and tristearin. The resulting nanoparticles had an anisometric shape and a platelet-like structure. Curcuminoid-loaded trimyristin particles did not solidify when stored at room temperature. The supercooled state of trimyristin was studied by DSC and ¹H NMR experiments. A partial recrystallization of the lipid matrix was detected but no change of the mobility of the lipid was noted. Nanoparticles based on tristearin had an α- and β-modification which was subsequently converted into the stable β-phase. Curcuminoids did neither influence the melting behavior nor the crystalline or geometric structure of the particles. The interactions between the curcuminoids and the lipid matrix were investigated by Raman and fluorescence spectroscopy. The shape of the curcuminoid bands in the Raman spectra suggested that the drug was in an amorphous state. The fluorescence spectra showed an effect of the lipid matrix on fluorescence properties of the curcuminoids. It was further demonstrated that the drug was not secluded by the solid lipid matrix, but it was influenced by the surrounding aqueous environment. Fluorescence anisotropy measurements revealed a decreased mobility of the curcuminoids within the nanodispersions. From the results of Raman and fluorescence measurements it was concluded that the drug was mainly located on the surface of the crystalline particles.     

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers.     

Application of lipid nanoparticles to ocular drug delivery

ABSTRACT

Introduction: Although eye drops are widely used as drug delivery systems for the anterior segment of the eye, they are also associated with poor drug bioavailability due to transient contact time and rapid washout by tearing. Moreover, effective drug delivery to the posterior segment of the eye is challenging, and alternative routes of administration (periocular and intravitreal) are generally needed, the blood–retinal barrier being the major obstacle to systemic drug delivery.

Areas covered: Nanotechnology, and especially lipid nanoparticles, can improve the therapeutic efficiency, compliance and safety of ocular drugs, administered via different routes, to both the anterior and posterior segment of the eye. This review highlights the main ocular barriers to drug delivery, as well as the most common eye diseases suitable for pharmacological treatment in which lipid nanoparticles have proved efficacious as alternative delivery systems.

Expert opinion: Lipid-based nanocarriers are among the most biocompatible and versatile means for ocular delivery. Mucoadhesion with consequent increase in pre-corneal retention time, and enhanced permeation due to cellular uptake by corneal epithelial cells, are the essential goals for topical lipid nanoparticle delivery. Gene delivery to the retina has shown very promising results after intravitreal administration of lipid nanoparticles as non-viral vectors.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5?mg TS?g^?1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24?h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM?<?5% GD?<?5% SA?<?5% GB?<?2.5% GM?<?2.5% SA?<?10% GD?<?10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5?mg TS?g^?1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5?mg TS?g^?1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

PURPOSE: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system. METHODS: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5 mg TS g(-1). Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24 h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated. RESULTS: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7-95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM < 5% GD < 5% SA < 5% GB < 2.5% GM < 2.5% SA < 10% GD < 10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB-2.5 mg TS g(-1) SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB-2.5 mg TS g(-1) stored at 5 degrees C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation. CONCLUSIONS: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.     

Effect of nanoparticles on transdermal drug delivery

The purpose of the present study was to assess by in vitro means the effect of poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles on transdermal drug delivery. Methanol and octanol were chosen as test permeants. In order to distinguish between thermodynamic effect and those due to biological consequences, two different membranes were employed, i.e., full thickness hairless mouse skin and silicone elastomer sheeting (175 microns). It is evident that poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles increase the permeability of methanol through hairless mouse skin by a factor of 1.2-2. The permeability of lipophilic octanol is either unaffected by nanoparticles or decreases as a function of nanoparticle concentration depending on the lipophilicity of the polymer material.     

Lung-targeting delivery of dexamethasone acetate loaded solid lipid nanoparticles

The objective of the present study was to develop a novel solid lipid nanoparticle (SLN) for the lung-targeting delivery of dexamethasone acetate (DXM) by intravenous administration. DXM loaded SLN colloidal suspensions were prepared by the high pressure homogenization method. The mean particle size, drug loading capacity and drug entrapment efficiency (EE%) of SLNs were investigated. In vitro drug release was also determined. The biodistribution and lung-targeting efficiency of DXM-SLNs and DXM-solutions (DXM-sol) in mice after intravenous administration were studied using reversed-phase high-performance liquid chromatography (HPLC). The results (expressed as mean +/- SD) showed that the DXM-SLNs had an average diameter of 552 +/- 6.5 nm with a drug loading capacity of 8.79 +/- 0.04% and an entrapment efficiency of 92.1 +/- 0.41%. The in vitro drug release profile showed that the initial burst release of DXM from DXM-SLNs was about 68% during the first 2 h, and then the remaining drug was released gradually over the following 48 hours. The biodistribution of DXM-SLNs in mice was significantly different from that of DXM-sol. The concentration of DXM in the lung reached a maximum level at 0.5 h post DXM-SLNs injection. A 17.8-fold larger area under the curve of DXM-SLNs was achieved compared to that of DXM-sol. These results indicate that SLN may be promising lung-targeting drug carrier for lipophilic drugs such as DXM.