Lipid nanoparticles: state of the art,new preparation methods and challenges in drug delivery

Introduction: Nanoparticles are rapidly developing as drug carriers because of their size-dependent properties. Lipid nanoparticles (LNPs) are widely employed in drug delivery because of the biocompatibility of the lipid matrix.

Areas covered: Many different types of LNPs have been engineered in the last 20 years, the most important being solid lipid nanoparticles (SLNs), nanostrucured lipid carriers (NLCs), lipid–drug conjugates (LDCs) and lipid nanocapsules (LNCs). This review gives an overview of LNPs, including their physico-chemical properties and pharmacological uses. Moreover, it highlights the most important innovations in the preparation techniques of LNPs, aimed to encapsulate different molecules within the lipid matrix. Finally, it gives a short perspective on the challenges of drug delivery, which are a potential field of application for LNPs: cancer therapy, overcoming the blood–brain barrier and gene and protein delivery.

Expert opinion: LNPs are a safe and versatile vehicles for drug and active delivery, suitable for different administration routes. New technologies have been developed for LNP preparation and studies are currently underway in order to obtain the encapsulation of different drugs and to deliver the active molecule to the site of action.     

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。     

Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations.

Aqueous dispersions of lipid nanoparticles are being investigated as drug delivery systems for different therapeutic purposes. One of their interesting features is the possibility of topical use, for which these systems have to be incorporated into commonly used dermal carriers, such as creams or hydrogels, in order to have a proper semisolid consistency. For the present investigation four different gel-forming agents (xanthan gum, hydroxyethylcellulose 4000, Carbopol943 and chitosan) were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles--solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)--made from tripalmitin were prepared by hot high pressure homogenization and then incorporated into the freshly prepared hydrogels. NLC differ from SLN due to the presence of a liquid lipid (Miglyol812) in the lipid matrix. Lipid nanoparticles were physically characterized before and after their incorporation into hydrogels. By means of rheological investigations it could be demonstrated that physical properties of the dispersed lipid phase have a great impact on the rheological properties of the prepared semisolid formulations. By employing an oscillation frequency sweep test, significant differences in elastic response of SLN and NLC aqueous dispersions could be observed.     

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals

INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.     

溶致液晶的制备、表征以及作为药物载体的应用

脂质已经被广泛地用作多种药物传递系统中的主要组分,例如脂质体、固体脂质纳米粒、纳米结构脂质载体和溶致液晶。其中,溶致液晶具有高度的有序性和热力学稳定的内部纳米结构,从而具有作为持续释放药物模型的潜力。立方相和六角相的复杂结构已经被证实能够为活性药物原料（不同的相对分子质量和极性）提供由扩散控制的释放。此外,脂质的生物可降解性和生物相容性证明了其具有最小的毒性并且可应用于多种给药途径。因此,近几年对溶致液晶的研究已经吸引了很多研究者的关注。本文将对溶致液晶的结构特点、制备方法、表征进行综述。此外,溶致液晶作为药物传递系统的最新研究进展将被进一步讨论。     

Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

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。     

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.     

Exploitation of lipid-polymeric matrices at nanoscale for drug delivery applications

ABSTRACT

Introduction: Progress in drug delivery and a better quality of life for patients, relies on the development of new and suitable drug carrier systems, with unequivocal therapeutic benefits, low systemic toxicity and reduced side effects. Lipid-polymeric nanoparticles have been explored to produce nanocarriers due to their features and applications such as high drug entrapment, physical-chemical stability and controlled release properties.

Areas covered: In this review, we describe several hybrid nanoparticles obtained from mixing a polymer with a lipid matrix. This association can potentiate the efficacy of drug delivery systems, due to the enhancement of encapsulation efficiency and loading capacity, tailoring the drug release according to the therapeutic purpose, and improving the drug uptake by targeting it to specific receptors. Contrary to lipid nanoparticles, these hybrid nanoparticles can decrease the initial burst release and promote a more sustained and localized release of the drug.

Expert Opinion: Lipid-polymeric nanoparticles are versatile vehicles for drug delivery by different administration routes in the treatment of multiple diseases. Different solid lipids, polymers, surfactants and techniques for producing these carriers have been investigated, revealing the importance of their composition to achieve optimal characteristics to drug delivery.     

Solid lipid nanocarriers in drug delivery: characterization and design

Introduction: Solid lipid nanoparticles are promising drug carriers for systemic circulations as well as local applications. One of the major challenges for drug delivery is designing nanocarriers for efficient delivery of active substances to the target site and facilitating drug absorption.

Areas covered: In this article, the effects of excipients and particle preparation methods on the properties of solid lipid nanocarriers (SLNCs) and their impact on drug absorption and efficacies related to different administration routes are reviewed and discussed.

Expert opinion: SLNCs have special characteristics, making them attractive as drug delivery systems, for parenteral and oral delivery for systemic effects, or ocular, pulmonary and topical delivery to enhance local treatment efficacy and reducing systemic side effects. Both excipients and fabrication methods are crucial for the function and size of nanoparticles and should be considered simultaneously in designing particles to obtain the optimal drug absorption and efficacy, especially for local treatments. Despite the demonstrated advantages by the preclinical studies, further studies on improved understanding of the interactions of SLNCs with biological tissues of the target site is necessary for efficient designing functional nanoparticles for clinical applications.

Abbreviations: DG: diglycerides; FFA: free fatty acids; GMS: glyceryl monostearate; MG: monoglycerides; NLC: nanostructured lipid carriers; PL: phospholipids; SLM: solid lipid microparticles; SLN: solid lipid nanoparticles; SLNC: solid lipid nanocarriers; TG: triglycerides.     

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。     

Features,applications, and sustainability of lipid nanoparticles in cosmeceuticals

Cosmeceuticals are a branch of cosmetic products that forms a bridge between cosmetic and drug products. It is a fast-growing branch of the cosmetic industry, especially after the introduction of novel formulation and manufacturing techniques such as lipid nanoparticles (LNPs). These LNPs-based cosmeceutical products offer several advantages such as enhanced bioavailability of cosmeceutical active ingredients (CAIs), improved aesthetic appeal, and stability of the final products. However, the use of these LNPs may raise some concerns about possible side effects of these LNPs and potential hazards to the customer’s health. Accordingly, an update that focuses on the use of this important branch of nanoparticles is necessary since most review papers are dealing with all types of nanocarriers in the same review with little focus on LNPs. Therefore, in the current review, a detailed analysis of the advantages and disadvantages of LNPs in this field was highlighted, to emphasize the LNPs-based cosmeceuticals on the market, as well as the potential risk posed by LNPs on exposure and recently introduced regulatory guidelines to address them. In addition, if these products can be a candidate as products that meet the sustainable development goals raised by the UN are discussed.     

Perspectives on cutting-edge nanoparticulate drug delivery technologies based on lipids and their applications

Numerous nanotech arenas in therapeutic biology have recently provided a scientific platform to manufacture a considerable swath of unique chemical entities focusing on drugs. Recently, nanoparticulate drug delivery systems have emerged to deliver a specific drug to a specified site. Among all other carriers, lipids possess features exclusive to nanostructured dosage forms. The bioavailability of orally administered drugs is typically negatively affected by their poor water solubility, resulting from the unique chemical moieties introduced. Because of their unique advantages, lipid nanoparticles must become increasingly predictable as a robust delivery mechanism. The enhanced biopharmaceutical properties and significance of lipid-based targeting technologies such as liposomes, niosomes, solid lipid nanoparticles and micelles are highlighted in this review. Pharmaceutical implications of lipid nanocarriers for the transport and distribution of various therapeutic agents, such as biotechnological products and small pharmaceutical molecules, is a booming topic. Lipid nanoparticles as drug delivery systems have many appealing properties, including high biocompatibility, ease of preparation, tissue specificity, avoidance of reticuloendothelial systems, delayed drug release, scale-up feasibility, nontoxicity and targeted delivery. The use of lipid nanoparticles to enhance the transport of biopharmaceuticals is currently considered state-of-the-art. Similarly, we critically examine the upcoming guidelines that therapeutic scientists should handle.     

Nanostructured materials in drug and gene delivery: a review of the state of the art

A wide variety of drug delivery systems have been developed, each with its own advantages and limitations, but the important goals of all of the systems are to enhance bioavailability, reduce drug toxicity, target to a particular organ, and increase the stability of the drug. The development of nanostructured drug carriers have grasped increased attention from scientific and commercial organizations due to their unique ability to deliver drugs and challenging molecules such as proteins and nucleic acids. These carriers present many technological advantages such as high carrier capacity, high chemical and biological stability, feasibility of incorporating both hydrophilic and hydrophobic substances, and their ability to be administered by a variety of routes (including oral, inhalational, and parenteral) to provide controlled/sustained drug release. Moreover, applications of nanoparticulate formulations in enhancing drug solubility, dissolution, bioavailability, safety, and stability have already been proven. In the view of their multifaceted applications, the present review aims to discuss and summarize some of the interesting findings and applications, methods of preparation, and characterization of various nanostructured carriers useful in drug delivery. Included in this discussion are polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, cyclodextrins, fullerenes, gold and silica nanoparticles, and quantum dots. Because there are likely to be new applications for nanoparticles in drug delivery, they are expected to solve many problems associated with the delivery of drugs and biomolecules through different delivery routes.     

Nanostructured lipid carriers system: Recent advances in drug delivery

Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.     

Nanocarriers for dermal drug delivery: Influence of preparation method, carrier type and rheological properties

Nanocarriers are highly interesting delivery systems for the dermal application of drugs. Based on a eudermic alkylpolyglycosid nanoemulsions, solid lipid nanoparticles (SLN) and nano-structured lipid carriers (NLC) were prepared by ultrasonic dispersion. The ultrasound preparation technique turned out to be convenient and rapid. For reasons of comparison, nanoemulsions were also prepared by high-pressure homogenisation with highly similar physicochemical properties. Cryo electron microscopy was employed to elucidate the microstructure of the ultrasound-engineered nanocarriers. Furthermore, in vitro skin experiments showed excellent skin permeation and penetration properties for flufenamic acid from all formulations. Moreover, ATR-FTIR studies revealed barrier-restorative properties for NLC and SLN. Furthermore, the rheological characteristics of all nanocarriers were determined. In order to increase the viscosity, three different polymers were employed to also prepare semi-solid NLC drug delivery systems. All of them exhibited comparable skin diffusion properties, but may offer improved dermal applicability.     

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.     

Physical chemical considerations of lipid-based oral drug delivery--solid lipid nanoparticles

Of all the methods employed by formulators when presented with the task of improving oral bioavailability, the use of lipid assemblies is perhaps the least understood. Nonetheless, lipid-based formulations, and in particular solid lipid nanoparticles (SLN), show great promise for enhancing the oral bioavailability of some of the most poorly absorbed compounds. The physical/chemical characteristics of lipid-based systems are highly complex because of the existence of a variety of lipid assembly morphologies, the morphology-dependent solubility of drug, the interconversion of assembly morphology as a function of time and chemical structure, and the simultaneous lipid digestion. The present work will center on recent studies of the relevant physicochemical characteristics of SLN, most notably solubility of the drug in the lipid matrix, location of the drug in the aggregate, drug release properties of the aggregate, and particle size stability. Strengths and weaknesses of the lipid assemblies, in particular solid lipid nanoparticles, in promoting drug delivery by the oral route for systemic or Peyer's patch uptake will be highlighted, and possible future research pathways will be suggested.     

Solid lipid nanoparticles as vehicles of drugs to the brain: Current state of the art

Central nervous system disorders are already prevalent and steadily increasing among populations worldwide. However, most of the pharmaceuticals present on world markets are ineffective in treating cerebral diseases, because they cannot effectively cross the blood brain barrier (BBB). Solid lipid nanoparticles (SLN) are nanospheres made from biocompatible solid lipids, with unique advantages among drug carriers: they can be used as vehicles to cross the BBB. This review examines the main aspects surrounding brain delivery with SLN, and illustrates the principal mechanisms used to enhance brain uptake of the delivered drug.