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。     

离心超滤法测定石杉碱甲固体脂质纳米粒的包封率

固体脂质纳米粒（Solid lipid nanoparticles,SLN）其最大特点是采用生理相容性好、毒性低的脂质材料为载体,降低了其对人体的毒副作用同时,既具备聚合物纳米粒的高物理稳定性、药物泄漏慢的优势．又兼具了脂质体、乳剂的低毒性,可大规模生产的特点。模型药石杉碱甲（HuperzineA,HupA）为高效、高选择性、可逆性的乙酰胆碱酯酶抑制剂,     

新型纳米粒给药系统——纳米结构的脂质载体

固体脂质纳米粒（SLN）已被公认是一种新型的纳米粒给药系统，但SLN有不同程度的潜在问题。作为新一代的纳米粒给药系统——纳米结构的脂质载体（Nanostructured lipid carriers，NLC）可减小或者避免SLN有限载药能力及储藏过程包封药物泄漏的问题，而且能调整SLN的释放曲线。NLC以固体脂质与物态上相异的液体脂质混合制备得到，形成3种类型特殊结构的脂质骨架：结晶不完全态、无定形态、复合态。现介绍一种特殊的制备方法，不仅适合于制备NLC，而且也可作为制备高粒子浓度（30％～95％）SLN分散液的方法。描述了NLC作为给药系统潜在的应用前景。     

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。     

固体脂质纳米粒的制备与应用研究进展

固体脂质纳米粒（solid lipid nanoparticles，SLN）是20世纪90年代发展起来的一种性能优异的新型纳米粒给药系统。其以固态类脂化合物（天然或合成）为载体，将药物包裹于类脂核中制成固态胶粒，既具有传统载体系统的优点，同时也改善了不足之处。SLN有多种制备方法，可经多种途径给药，有其特殊的优越性，在新药开发中极具发展前景。本文就国内外关于SLN的制备方法及应用方面的最新研究作一综述。     

固体脂质纳米粒在中药经皮给药中的研究进展

目的:介绍固体脂质纳米粒作为载体应用于中药经皮给药的研究进展。方法:以"固体脂质纳米粒""中药""经皮给药""纳米载体""Solid lipid nanoparticles""Traditional Chinese medicine""Transdermal drug delivery""Nano-carrier"等为关键词,组合查询2000-2014年Pub Med、中国知网全文数据库、维普中文期刊数据库和万方数据库中有关固体脂质纳米粒的常用脂质材料、透皮机制、优劣势及其在中药经皮给药研究进展的相关文献并进行综述。结果与结论:共查阅文献167篇,有效文献32篇。固体脂质纳米粒常用脂质材料为甘油三酯、甘油酯、类胆固醇等,经皮给药时常用表面活性剂有豆磷脂、卵磷脂等。其透皮机制尚不明确,可提高药物物理稳定性、提高难溶性药物生物利用度、降低药物刺激性,同时具有促渗、缓释、靶向作用。其劣势为载药量相对较低。现已有鬼臼毒素、灯盏花素、雷公藤内酯醇、青藤碱固体脂质纳米粒等用于经皮给药中。存在的不足有药物包载有限以及在安全性和有效性方面尚缺乏系统评价等,尚需深入研究。     

正交设计优化伊曲康唑固体脂质纳米粒的处方组成与制备工艺

目的:制备伊曲康唑固体脂质纳米粒(itraconazole solid lipid nanoparticles,ITZ-SLNs)并对其进行物相分析以确定纳米粒的形成。方法:以伊曲康唑(ITZ)为模型药物,硬脂酸为载体材料,采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN),正交试验设计优化处方组成和制备工艺,并对纳米粒的结构形态、粒径、表面电位、包封率、体外释药特性等进行了研究。结果:以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,Zeta电位为-(37.06±0.53)mV,包封率为(92.11±1.60)%,药物体外释放符合Higuchi方程,经DSC分析证明纳米粒确已形成。结论:伊曲康唑固体脂质纳米粒有望成为新型缓释纳米给药系统。     

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.     

固体脂质纳米粒的研究新进展

固体脂质纳米粒是近年来很受重视的一种新型药物传递载体,具有靶向、控释、提高药物稳定性、毒性小、可大批量生产等优点,是一种极有发展前景的新型给药系统.现综述了近年来国内外固体脂质纳米粒的制备技术、作为药物载体的应用、存在问题以及发展前景.     

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。     

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): recent advances in drug delivery

Solid lipid-based nanoparticles (SLBNs) were developed as potential alternatives to other conventional drug delivery systems such as polymeric nanoparticles, liposomes, and emulsions. In general, SLBNs are divided into two types: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs are distinguishable from NLCs by the composition of solid particle matrix. SLBNs can be prepared by several methods including high pressure homogenization, solvent emulsification (or diffusion)-evaporation, and microemulsion technologies. Then, SLBNs can be characterized in terms of particle size distribution, surface charge, morphology, and crystallinity. SLBNs are well-tolerated and efficient carrier systems for parenteral, oral, inhalational, ocular, and dermal applications. This review provides an overview of the preparation and characterization technologies for SLBNs and focuses on recent advances in drug delivery using SLBNs.     

Nanostructured lipid carriers for intraocular brimonidine localisation: development,in-vitro and in-vivo evaluation

Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97?±?1.98?nm, negative zeta potential (ZP) of ?44.2?±?7.81?mV, % entrapment efficiency (EE) of 83.631?±?0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4?°C for 3?months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (?13.14?±?1.28?mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.     

Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release

Topotecan is an important cytotoxic drug that has gained broad acceptance in clinical use for the treatment of refractory ovarian and small-cell lung cancer. The lactone active form of topotecan can be hydrolyzed in vivo, decreasing the drug’s therapeutic efficacy. Lipid encapsulation may promote in vivo stabilization by removing topotecan from aqueous media. Earlier reports of topotecan lipid nanoencapsulation have focused on liposomal encapsulation; however, the higher stability and cost-effectiveness of solid lipid nanoparticles (SLN) highlight the potential of these nanoparticles as an advantageous carrier for topotecan. The initial motivation for this work was to develop, for the first time, solid lipid nanoparticles and nanostructured lipid carriers (NLC) with a high drug loading for topotecan. A microemulsion technique was employed to prepare SLNs and NLCs and produced homogeneous, small size, negatively charged lipid nanoparticles with high entrapment efficiency and satisfactory drug loading. However, low recovery of topotecan was observed when the microemulsion temperature was high and in order to obtain high quality nanoparticles, and precise control of the microemulsion temperature is critical. Nanoencapsulation sustained topotecan release and improved its chemical stability and cytotoxicity. Surprisingly, there were no significant differences between the NLCs and SLNs, and both are potential carriers for topotecan delivery.     

SLN, NLC, LDC: state of the art in drug and active delivery

Drug delivery system focuses on the regulation of the in vivo dynamics, in order to improve the effectiveness and safety of the incorporated drugs by use of novel drug formulation technologies. Lipids such as fatty acids, triglycerides, vegetable oils and their derivatives, used for developing multiparticulate dosage forms, may be available in solid, semi-solid or liquid state. Solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid drug conjugate (LDCs) nanoparticles are novel lipid drug delivery systems. They were devised to address some of the challenges of conventional drug delivery systems ranging from low drug encapsulation efficiency to low bioavailability of Biopharmaceutical Classification Systems (BCS) class II and class IV drugs. SLNs are based on melt-emulsified lipids, which are solid at room temperature and consist of physiologically well tolerated ingredients often generally recognised as safe. NLCs are colloidal carriers characterized by a solid lipid core consisting of a mixture of solid and liquid lipids, and having a mean particle size in the nanometer range. LDC are nanoparticles contain drugs linked to lipid particles. This minireview highlights these three different but related technologies in lipid drug delivery. The objectives of their introduction, current applications, major challenges and some patented formulations are highlighted.     

Lipid nanoparticles for chemotherapeutic applications: strategies to improve anticancer efficacy

INTRODUCTION: Chemotherapy remains the major form of treatment for cancer. However, chemotherapy often fails due to a variety of barriers, resulting in a limited intratumoral drug disposition. Recently, lipid nanoparticles (LNs, i.e., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)) have been shown to provide a favorable means for efficiently delivering drugs to tumor sites, while minimizing their side effects. AREAS COVERED: The delivery of drugs to tumors is restricted by a series of barriers, including the tumor abnormalities, strong adverse effects and poor specificity of cytotoxic drugs, and the induction of multidrug resistance (MDR). The present review summarizes the strategies using SLNs and/or NLCs to improve the anticancer efficacy of cytotoxic drugs, including passive targeting, active targeting, long circulating and MDR reversing. Specifically, the most significant in vitro and in vivo results on the use of SLNs and/or NLCs are highlighted. EXPERT OPINION: The future success of SLNs and NLCs for administration of cytotoxic drugs will depend on their ability to efficiently encapsulate and release drugs, the possibility for large-scale production, selective tumor cells targeting and increased antitumor efficacy with reduced tissue toxicity.     

Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a comparison of solid lipid nanoparticles and nanostructured lipid carriers for dual drugs delivery

Context: Glioma is a common malignant brain tumor originating in the central nervous system. Efficient delivery of therapeutic agents to the cells and tissues is a difficult challenge. Co-delivery of anticancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment.

Objective: In this study, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were constructed for co-delivery of vincristine (VCR) and temozolomide (TMZ) to develop the synergetic therapeutic action of the two drugs. The antitumor effects of these two systems were compared to provide a better choice for gliomatosis cerebri treatment.

Methods: VCR- and TMZ-loaded SLNs (VT-SLNs) and NLCs (VT-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE) and drug loading capacity were evaluated. The single TMZ-loaded SLNs and NLCs were also prepared as contrast. Anti-tumor efficacies of the two kinds of carriers were evaluated on U87 malignant glioma cells and mice bearing malignant glioma model.

Results: Significantly better glioma inhibition was observed on NLCs formulations than SLNs, and dual drugs displayed the highest antitumor efficacy in vivo and in vitro than all the other formulations used.

Conclusion: VT-NLCs can deliver VCR and TMZ into U87MG cells more efficiently, and inhibition efficacy is higher than VT-SLNs. This dual drugs-loaded NLCs could be an outstanding drug delivery system to achieve excellent therapeutic efficiency for the treatment of malignant gliomatosis cerebri.     

Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs?

In recent years, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are among the popular research topics for the delivery of lipophilic drugs. Although SLNs have demonstrated several beneficial properties as drug-carrier, limited drug-loading and expulsion of drug during storage led to the development of NLCs. However, the superiority of NLCs over SLNs has not been fully established yet due to the contradictory results. In this study, SLNs and NLCs were developed using clotrimazole as model drug. Size, polydispersity index (PI), zeta potential (ZP), drug-loading (L), drug encapsulation efficiency (EE), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), drug release and stability of SLNs and NLCs were compared. Critical process parameters exhibited significant impact on the nanoparticles' properties. Size, PI, ZP and EE of the developed SLNs and NLCs were<100 nm, <0.17, <-22 mV and>82%, respectively. SEM images of SLNs and NLCs revealed spherical shaped particles (≈ 100 nm). DSC and XRD studies indicated slight difference between SLNs and NLCs as well as disappearance of the crystalline peak(s) of the encapsulated drug. NLCs demonstrated faster drug release than SLNs at low drug-loading, whereas there was no significant difference in drug release from SLNs and NLCs at high drug-loading. However, sustained/prolonged drug release was observed from both formulations. Furthermore, this study suggests that the drug release experiment should be designed considering the final application (topical/oral/parenteral) of the product. Regarding stability, NLCs showed better stability (in terms of size, PI, EE and L) than SLNs at 25°C. Moreover, there was no significant difference in drug release profile of NLCs after 3 months storage in compare to fresh NLCs, while significant change in drug release rate was observed in case of SLNs. Therefore, NLCs have an edge over SLNs.     

Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years.KEY WORDS: Nose-to-brain delivery, Intranasal administration, Nanostructured lipid carriers, NLC, Solid lipid nanoparticles, SLN, Nanoemulsions, In vivo studies, Pharmacokinetic, Pharmacodynamics     

Nanostructured lipid carriers,solid lipid nanoparticles,and polymeric nanoparticles: which kind of drug delivery system is better for glioblastoma chemotherapy?

Context: Glioblastoma is a malignant brain tumor originating in the central nervous system. Successfully therapy of this disease required the efficient delivery of therapeutic agents to the tumor cells and tissues. Delivery of anticancer drugs using novel nanocarriers is promising in glioma treatment.

Objective: Polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were constructed for the delivery of temozolomide (TMZ). The anti-tumor effects of the three kinds of nanocarriers were compared to provide the optimum choice for gliomatosis cerebri treatment.

Methods: TMZ-loaded PNPs (T-PNPs), SLNs (T-SLNs), and NLCs (T-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE), and drug loading (DL) capacity were evaluated. Anti-tumor efficacies of the three kinds of nanocarriers were evaluated on U87 malignant glioma cells (U87?MG cells) and mice-bearing malignant glioma model.

Results: T-NLCs displayed the best anti-tumor activity than other formulations in vivo and in vitro. The most significantly glioma inhibition was observed on NLCs formulations than PNPs and SLNs.

Conclusion: This work demonstrates that NLCs can deliver TMZ into U87MG cells more efficiently, with higher inhibition efficacy than PNPs and SLNs. T-NLCs could be an excellent drug delivery system for glioblastoma chemotherapy.