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。     

固体脂质纳米粒的研究进展

目的综述固体脂质纳米粒的最新研究进展。方法以国内外大量有代表性的论文为依据,将固体脂质纳米粒的制备方法、特性分析、药物载入、药物释放及应用情况进行了概括,指出了发展前景和尚待解决的问题。结果固体脂质纳米粒的多种制备方法各有优、缺点,调整制备参数可调整药物的包封率和释药曲线。结论固体脂质纳米粒可供多途径给药,是极有发展前景的新型给药系统。     

固体脂质纳米粒制备及应用研究进展

目的综述固体脂质纳米粒制备及应用进展。方法以国内外有代表性的文献和资料为依据,将固体脂质纳米粒的制备及应用等情况进行了分析与归纳。结果固体脂质纳米粒的多种制备方法各有优、缺点,其中以高压乳匀法和微乳法被推崇。调整制备参数可调整药物的包封率和释药曲线。结论固体脂质纳米粒是一种性能优异、有发展前景的新型给药系统。     

固体脂质纳米粒的制备和载体结构的研究进展及其应用

目的:从固体脂质纳米载体的制备和结构特征方面介绍其研究进展.方法:以国内外大量有代表性的论文为依据进行分析、归纳整理.结果:固体脂质纳米粒的多种制备方法各有优缺点,其中以高压乳化法和微乳化法被推崇.以固体和液体的混合脂质为基材,制备出O/F/W结构的纳米粒,不但能够有较好的载药能力,还可以拥有优异的缓控释功能.结论:固体脂质纳米粒是一种性能优异、有发展前景的新型给药系统.     

固体脂质纳米粒的研究概述

目的：从固体脂质纳米载体的制备和剂型应用等方面阐述其研究进展情况。方法：以国内外大量有代表性的论文为依据进行分析、归纳整理。结果：固体脂质纳米粒的多种制备方法各有优缺点，以高压乳化法、微乳法较好，其低毒、靶向性好、缓控释药物能力强等优点决定其在剂型应用方面有很大潜力。结论：固体脂质纳米粒是一种有巨大发展前景的新型给药系统。     

固体脂质纳米粒的制备与应用

介绍固体脂质纳米粒作为药物载体的发展现状.以国外有代表性的文献资料为依据,进行分析和归纳,综述了固体脂质纳米粒的制备工艺、理化性质、稳定性及应用,指出固体脂质纳米粒作为药物载体,具有广阔应用前景.     

新型纳米结构脂质载体系统的研究进展

目的介绍新型的纳米结构脂质载体系统的研究进展,为其研究和应用提供参考。方法查阅相关文献33篇,进行整理和归纳。结果新型的纳米结构脂质载体能够克服固体脂质纳米粒的一些不足,并具有独特的结构特征,药物的包封机理和释放特征。结论纳米结构脂质载体作为药物传递系统的一种新剂型,具有广阔的发展前景。     

表面修饰脂质纳米粒给药系统的研究进展

脂质纳米粒是一种极具潜力的新型药物传输载体,对脂质纳米粒表面修饰是近年来的研究热点。通过表面修饰的手段能有效的避免单核巨噬细胞的吞噬、延长脂质纳米粒在体内的循环时间、主动靶向于病灶部位。本文就脂质纳米粒的体内命运及脂质纳米粒表面修饰的研究进展做一综述。     

纳米结构脂质载药系统的研究进展

纳米结构脂质载体是在第一代脂质纳米粒——固体脂质纳米粒的基础上发展起来的一种新型药物传递系统,相比于传统脂质纳米粒,具有安全性好、稳定性高等优势,故而引起国内外医药工作者的广泛关注。对纳米结构脂质载体的特点、性质、结构、制备工艺及其用作载药系统的研究情况进行概述,为其在医药领域中的深度开发提供参考。     

非洛地平-硬脂酸固体脂质纳米粒的制备及其体外透皮吸收研究

目的:以固体脂质纳米粒为栽体,通过透皮给药达到提高非洛地平透皮吸收及缓释长效的目的.方法:采用溶剂挥发-超声法制备非洛地平固体脂质纳米粒水分散体,以大鼠皮肤为渗透屏障对非洛地平固体脂质纳米粒的经皮渗透进行研究.结果:非洛地平-硬脂酸固体脂质纳米粒为类球形实体粒子,平均粒径范围在50～150 nm,包封率大于85%,栽药量大于7%,药物体外释放符合一级动力学过程.体外经皮渗透速率显著高于空白对照组.结论:非洛地平固体脂质纳米粒处方设计合理,制备工艺可靠,以纳米粒作为透皮给药载体具有广阔的发展前景.     

Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers

The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.     

Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art.

Solid lipid nanoparticles (SLN) introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipients, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted. References of the most relevant literature published by various research groups around the world are provided.     

Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.     

Solid lipid nanoparticles (SLN) for controlled drug delivery II. drug incorporation and physicochemical characterization

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.     

Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems

Solid lipid nanoparticles (SLN) have attracted increasing attention by various research groups and companies since the early 1990s. Their advantages over existing traditional carriers have been clearly documented. In addition, modified SLN have been described which are nanostructured lipid carriers (NLC) composed of liquid lipid blended with a solid lipid to form a nanostructured solid particle matrix. NLC combine controlled release characteristics with some advantages over SLN. This paper reviews the production techniques, characterization and physical stability of these systems including destabilizing factors and principles of drug loading, then considers aspects and benefits of SLN and NLC as colloidal drug carriers.     

Production of solid lipid nanoparticles (SLN): scaling up feasibilities.

Solid lipid nanoparticles (SLN/Lipopearls) are widely discussed as a new colloidal drug carrier system. In contrast to polymeric systems, such as Polylactic copolyol microcapsules, these systems show with a good biocompatibility, if applied parenterally. The solid lipid matrices can be comprised of fats or waxes, and allow protection of incorporated active ingredients against chemical and physical degradation. The SLN can either be produced by 'hot homogenization' of melted lipids at elevated temperatures or by a 'cold homogenization' process. This paper deals with production technologies for SLN formulations, based on non-ethoxylated fat components for topical application and high pressure homogenization. Based on the chosen fat components, a novel and easy manufacturing and scaling-up method was developed to maintain chemical and physical integrity of the encapsulated active ingredients in the carrier.     

Production of solid lipid nanoparticles (SLN): scaling up feasibilities

Solid lipid nanoparticles (SLN/Lipopearls) are widely discussed as a new colloidal drug carrier system. In contrast to polymeric systems, such as Polylactic copolyol microcapsules, these systems show with a good biocompatibility, if applied parenterally. The solid lipid matrices can be comprised of fats or waxes, and allow protection of incorporated active ingredients against chemical and physical degradation. The SLN can either be produced by 'hot homogenization' of melted lipids at elevated temperatures or by a 'cold homogenization' process. This paper deals with production technologies for SLN formulations, based on non-ethoxylated fat components for topical application and high pressure homogenization. Based on the chosen fat components, a novel and easy manufacturing and scaling-up method was developed to maintain chemical and physical integrity of the encapsulated active ingredients in the carrier.     

SLN and NLC for topical delivery of ketoconazole

The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol 888 ATO as solid lipid. The natural antioxidant alpha-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.     

Liquid and semisolid SLN dispersions for topical application: rheological characterization.

Aqueous dispersions of solid lipid nanoparticles (SLN) are promising drug carrier systems for topical application. A drawback, however, is the need of incorporating the SLN dispersion in commonly used dermal carriers (creams, gels) to obtain the required semisolid consistency for dermal application. This study describes the production of SLN dispersions having the desired semisolid consistency by a one-step process. Physical characterization of these systems in terms of particle size and rheological properties revealed some interesting features. Despite the high lipid content it was possible to produce colloidal dispersions by high pressure homogenization. Continuous flow measurements revealed systems with yield point, plastic flow and thixotropy. Oscillation measurements proved the viscoelastic microstructure of the SLN dispersions. Higher concentrated SLN dispersions were found to have a prevailing elastic component in contrast to lower concentrated systems. Viscoelastic properties of a 40% SLN dispersion were found to be comparable to standard dermal preparations. Storage stability at room temperature in terms of particle size could be demonstrated over a 6-month period. The development of the gel structure of semisolid SLN dispersions is delayed comparable to commercial O/W creams with non-ionic emulsifiers. Parameters like concentration of the dispersed phase, particle size and particle shape were identified as significant factors influencing the microstructure of these complex semisolid systems.     

Idebenone loaded solid lipid nanoparticles interact with biomembrane models: calorimetric evidence

The knowledge of the interactions between solid lipid nanoparticles (SLN) and cell membranes is important to develop effective carrier systems for drug delivery applications. Loading idebenone (IDE), an antioxidant drug useful in the treatment of neurodegenerative diseases, into SLN improves IDE antioxidant activity in in vitro biological studies, but the mechanism by which IDE permeation through the blood-brain barrier (BBB) occurs are still unclear. Therefore, in this research, unloaded and IDE loaded SLN interaction with biomembrane models, consisting of dimyristoylphosphatidylcholine multilamellar vesicles (MLV), were studied by differential scanning calorimetry (DSC). In the experiments performed, unloaded and IDE loaded SLN where incubated with the biomembrane models and their interactions were evaluated through the variations in their calorimetric curves. The results of our DSC studies indicated that the SLN under investigation were able to go inside the phospholipid bilayers with a likely localization in the outer bilayers of the MLV from where they moved toward the inner layers by increasing the contact time between SLN and MLV. Furthermore, IDE loaded SLN were able to release IDE into the biomembrane model, thus facilitating IDE penetration into the bilayers while free IDE showed only a low ability to interact with this model of biomembranes. Our results suggest that these SLN could be regarded as a promising drug delivery system to improve IDE bioavailability and antioxidant activity.