Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs

Lipid-based formulations encompass a diverse group of formulations with very different physical appearance, ranging from simple triglyceride vehicles to more sophisticated formulations such as self-emulsifying drug delivery systems (SEDDS). Lipid-based drug delivery systems may contain a broad range of oils, surfactants, and co-solvents. They represent one of the most popular approaches to overcome the absorption barriers and to improve the bioavailability of poorly water-soluble drugs. Diversity and versatility of pharmaceutical grade lipid excipients and drug formulations as well as their compatibility with liquid, semi-solid and solid dosage forms make lipid systems most complex. Digestion of triglyceride lipids, physicochemical characteristics and solubilisation of lipid digestion products as well as intestinal permeability are some of the variable parameters of such formulations. Furthermore, among the factors affecting the bioavailability of the drug from lipid-based formulations are the digestion of lipid, the mean emulsion droplet diameter, the lipophilicity of the drug and the type of lipids. The solubility of the Active Pharmaceutical Ingredient in the Lipid System, the desorption/sorption isotherm and the digestibility of lipid vehicle are important issues to be considered for formulations of isotropic lipid formulations. This review also describes the fate of lipid formulations in the gut and the factors influencing the bioavailability from lipid-based formulations. Novel formulation systems and currently marketed products conclude this review.     

Lipid nanoparticles for parenteral delivery of actives

The present review compiles the applications of lipid nanoparticles mainly solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid drug conjugates (LDC) in parenteral delivery of pharmaceutical actives. The attempts to incorporate anticancer agents, imaging agents, antiparasitics, antiarthritics, genes for transfection, agents for liver, cardiovascular and central nervous system targeting have been summarized. The utility of lipid nanoparticles as adjuvant has been discussed separately. A special focus of this review is on toxicity caused by these kinds of lipid nanoparticles with a glance on the fate of lipid nanoparticles after their parenteral delivery in vivo viz the protein adsorption patterns.     

脂质类纳米载体在难溶性药物递送中的应用

随着新技术在药物研发中的广泛应用,大量有活性的难溶性候选药物涌现出来,但水溶性差的问题又严重制约了此类药物的开发。目前纳米载体作为难溶性药物递送系统的研究日益增多。本文综述了微乳、脂肪乳、脂质体、固体脂质纳米粒、纳米脂质载体、脂质纳米混悬剂和仿生载体等脂质类纳米载体在难溶性药物递送中的应用,旨在为产品的开发提供新策略。     

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.     

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 lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core. Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers’ formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary. This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.     

把握创新制剂推动我国药业发展新机遇

药物研发进入制剂创新时代,新型药物递送系统（drug delivery system,DDS）已成为新药研发热点。我国医药产业的持续、健康发展需要新分子实体（NME）与新制剂产品两个支柱共同支撑。基于目前我国医药产业的发展现状,NME研发适宜作为我国医药产业发展的长远战略,而现阶段发展策略则应以DDS创新作为领头军。DDS能够更迅速地形成战斗力、产业规模和竞争优势,在短期内成为医药产业发展的催化剂和推动力。我国医药企业需要重视并把握创新制剂所带来的新机遇。     

口服结肠释药系统的研究进展

目的:综述近年来口服结肠释药系统临床和药学研究动态,为今后在此领域的研究和临床应用提供参考。方法:通过对国内外相关文献资料的整理,对比和分析,总结口服结肠释药系统制剂进展和临床应用的发展方向。结果结论:口服结肠释药系统是通过口服给药,在结肠处定位释放药物的靶向制剂。此类制剂以其靶向释药方式和独特的临床使用价值,越来越广泛地引起了临床医生的关注,同时也成为药学研究领域的一大热点。     

Ceramic nanocarriers: versatile nanosystem for protein and peptide delivery

Introduction: Proteins and peptides have been established to be the potential drug candidate for various human diseases. But, delivery of these therapeutic protein and peptides is still a challenge due to their several unfavorable properties. Nanotechnology is expanding as a promising tool for the efficient delivery of proteins and peptides. Among numerous nano-based carriers, ceramic nanoparticles have proven themselves as a unique carrier for protein and peptide delivery as they provide a more stable, bioavailable, readily manufacturable, and acceptable proteins and polypeptide formulation.

Areas covered: This article provides an overview of the various aspects of ceramic nanoparticles including their classification, methods of preparation, latest advances, and applications as protein and peptide delivery carriers.

Expert opinion: Ceramic nanocarriers seem to have potential for preserving structural integrity of proteins and peptides, thereby promoting a better therapeutic effect. This approach thus provides pharmaceutical scientists with a new hope for the delivery of proteins and peptides. Still, considerable study on ceramic nanocarrier is necessary with respect to pharmacokinetics, toxicology, and animal studies to confirm their efficiency as well as safety and to establish their clinical usefulness and scale-up to industrial level.     

Natural and synthetic poly(malic acid)-based derivates: a family of versatile biopolymers for the design of drug nanocarriers

Abstract

The field of specific drug delivery is an expanding research domain. Besides the use of liposomes formed from various lipids, natural and synthetic polymers have been developed to prepare more efficient drug delivery systems either under macromolecular prodrugs or under particulate nanovectors. To ameliorate the biocompatibility of such nanocarriers, degradable natural or synthetic polymers have attracted the interest of many researchers. In this context, poly(malic acid) (PMLA) extracted from microorganisms or synthesized from malic or aspartic acid was used to prepare water-soluble drug carriers or nanoparticles. Within this review, both the preparation and the applications of PMLA derivatives are described emphasizing the in vitro and in vivo assays. The results obtained by several groups highlight the interest of such polyesters in the field of drug delivery.     

Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics

Introduction: For many years, the controlled delivery of therapeutic compounds has been a matter of great interest in the field of nanomedicine. Among the wide amount of drug nanocarriers, magnetic iron oxide nanoparticles (IONs) stand out from the crowd and constitute robust nanoplatforms since they can achieve high drug loading as well as targeting abilities stemming from their remarkable properties (magnetic and biological properties). These applications require precise design of the nanoparticles regarding several parameters which must be considered together in order to attain highest therapeutic efficacy.

Areas covered: This short review presents recent developments in the field of cancer targeted drug delivery using magnetic nanocarriers as drug delivery systems.

Expert opinion: The design of nanocarriers enabling efficient delivery of therapeutic compounds toward targeted locations is one of the major area of research in the targeted drug delivery field. By precisely shaping the structural properties of the iron oxide nanoparticles, drugs loaded onto the nanoparticles can be efficiently guided and selectively delivered toward targeted locations. With these goals in mind, special attention should be given to the pharmacokinetics and in vivo behavior of the developed nanocarriers.     

Monitoring of In Vitro Fat Digestion by Electron Paramagnetic Resonance Spectroscopy

Purpose The distribution of drugs between water, oil and mixed micelles after the oral application of lipid-based drug delivery systems affects their absorption rate. Since it has not been previously possible to monitor this process online during in vitro lipolysis, it was our aim to develop a suitable real-time method.Materials and Methods To follow the fate of a co-administered drug during fat digestion, the spin probe tempol benzoate was incorporated as a lipophilic model drug into a long-chain triglyceride (olive oil) and an in vitro digestion test was combined with electron paramagnetic resonance (EPR) spectroscopy (X-Band). Additionally the progression of digestion was determined by means of high performance thin layer chromatography (HPTLC).Results The spectral shape of the EPR spectrum changed significantly during the digestion process. EPR spectra at all times could be simulated with three species indicating a redistribution of the lipophilic model drug between olive oil, phosphate buffer and mixed micelles formed by bile salts and phospholipids.Conclusion This in vitro real-time analysis could be a very helpful tool to monitor the digestibility of novel lipid-based drug nanocarriers which is an important step to optimize and to predict drug delivery processes. In future the EPR monitoring of fat digestion will be transferred to in vivo experiments.     

Lipid - An emerging platform for oral delivery of drugs with poor bioavailability

The sole objective of pharmaceutical science is to design successful dosage forms which fulfill the therapeutic needs of the patients effectively. Development of new drug entities is posing real challenge to formulators, particularly due to their poor aqueous solubility which in turn is also a major factor responsible for their poor oral bioavailability. Lipids as carriers, in their various forms, have the potential of providing endless opportunities in the area of drug delivery due to their ability to enhance gastrointestinal solubilization and absorption via selective lymphatic uptake of poorly bioavailable drugs. These properties can be harvested to improve the therapeutic efficacy of the drugs with low bioavailability, as well as to reduce their effective dose requirement. The present communication embodies an in-depth discussion on the role of lipids (both endogenous and exogenous) in bioavailability enhancement of poorly soluble drugs, mechanisms involved therein, approaches in the design of lipid-based oral drug delivery systems with particular emphasis on solid dosage forms, understanding of morphological characteristics of lipids upon digestion, in vitro lipid digestion models, in vivo studies and in vitro-in vivo correlation.     

脂质聚合物杂化纳米粒的研究进展

目的：综述脂质聚合物杂化纳米粒的最新研究进展。方法：查阅近20年国内外有关脂质聚合物杂化纳米粒文献,对脂质聚合物杂化纳米粒的制备方法、主要影响因素及其应用现状进行总结。结果：核壳结构脂质聚合物杂化纳米粒兼具脂质体与聚合物纳米粒2种载体的优势,可一定程度改善脂质体和纳米粒存在的稳定性差、药物渗漏等不足。结论：脂质聚合物杂化纳米粒是一种性能优良,具有广阔发展前景的新型给药系统,但目前尚需对稳定性、在体药效及安全性等问题做深入研究。     

Recent advance of nanoparticle-based topical drug delivery to the posterior segment of the eye

Introduction: Considering that the number of patients afflicted by posterior eye diseases is increasing, effective drug delivery is currently in high clinical demand. Topical administration has been identified as the preferred option, while sufferingfrom multiple barriers. The development of nanoparticle-based drug delivery system provides an option, which would enhance the drug permeability across the barriers and achieve the desired drug level in the targeted tissue.

Areas covered: This review highlights the barrier to the posterior segment of the eye via topical administration. The up-to-date development of lipid nanoparticles, liposomes, emulsions, spanlastics, micelles, polymeric nanoparticles, layered double hydroxides (LDH), dendrimers, cyclodextrins(CDs), and prodrugs are summarized. Moreover, nanocarriers currently in clinical trials for posterior segment diseases have been discussed.

Expert opinion: Topical nanoparticle-based drug delivery systems have demonstrated significant progress. An ideal formulation should prolong retention time on the surface, enhance drug permeability through the ocular tissues, and efficiently deliver drugs to the targeted site. To design the rational targeting nanoparticle-based drug delivery system, a better understanding of the distribution of transporters and receptors on the eye is required. Ultimately, there is an urgent need to develop targeting hybrid drug delivery systems with the combination of the advantages of several nanocarriers.     

Nanotechnology in cancer therapy

Abstract

Cancer is one of the major causes of mortality worldwide and advanced techniques for therapy are urgently needed. The development of novel nanomaterials and nanocarriers has allowed a major drive to improve drug delivery in cancer. The major aim of most nanocarrier applications has been to protect the drug from rapid degradation after systemic delivery and allowing it to reach tumor site at therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as much as possible to reduce adverse effects. These nanocarriers are formulated to deliver drugs either by passive targeting, taking advantage of leaky tumor vasculature or by active targeting using ligands that increase tumoral uptake potentially resulting in enhanced antitumor efficacy, thus achieving a net improvement in therapeutic index. The rational design of nanoparticles plays a critical role since structural and physical characteristics, such as size, charge, shape, and surface characteristics determine the biodistribution, pharmacokinetics, internalization and safety of the drugs. In this review, we focus on several novel and improved strategies in nanocarrier design for cancer therapy.     

Designer nanoparticles: incorporating size,shape and triggered release into nanoscale drug carriers

Importance of the field: Although significant progress has been made in delivering therapeutic agents through micro and nanocarriers, precise control over in vivo biodistribution and disease-responsive drug release has been difficult to achieve. This is critical for the success of next generation drug delivery devices, as newer drugs, designed to interfere with cellular functions, must be efficiently and specifically delivered to diseased cells. The chief constraint in achieving this has been our limited repertoire of particle synthesis methods, especially at the nanoscale. Recent developments in generating shape-specific nanocarriers and the potential to combine stimuli-responsive release with nanoscale delivery devices show great promise in overcoming these limitations.

Areas covered in this review: How recent advances in fabrication technology allow synthesis of highly monodisperse, stimuli-responsive, drug-carrying nanoparticles of precise geometries is discussed. How particle properties, specifically shape and stimuli responsiveness, affect biodistribution, cellular uptake and drug release is also reviewed.

What the reader will gain: The reader is introduced to recent developments in intelligent drug nanocarriers and new nanofabrication approaches that can be combined with disease-responsive biomaterials. This will provide insight into the importance of controlling particle geometry and incorporating stimuli-responsive materials into drug delivery.

Take home message: The integration of responsive biomaterials into shape-specific nanocarriers is one of the most promising avenues towards the development of next generation, advanced drug delivery systems.     

Application of freeze-drying in the development of oral drug delivery systems

ABSTRACT

Introduction: With continual focus on oral drug delivery systems (ODDS), the role of freeze-drying becomes increasingly valuable. While freeze-drying is fundamentally a desiccation process, the advantageous material properties attributed to freeze-drying extend far beyond the preparation of stable pharmaceutical products. The formulation and process variables are important considerations as they affect the final freeze-dried product characteristics. It is of interest to expound on the principles and effects of freeze-drying in the hope of introducing novel products for applications in the development of ODDS.

Areas covered: In this review, basic principles, general formulation and process variables associated with freeze-drying will be covered. The application of freeze-drying in 3 areas: modification of active ingredients, development of novel freeze-dried excipients and development of freeze-dried final dosage forms will be discussed.

Expert opinion: As a pharmaceutical unit operation, freeze-drying has created new dimensions in the area of oral drug delivery, where the properties of the drugs, excipients and characteristics of the final solid dosage form can be modified by the freeze-drying process. With the emergence of new applications, the role of freeze-drying technology in ODDS is indeed a relevant and promising one.     

From conventional towards new – natural surfactants in drug delivery systems design: current status and perspectives

Importance of the field: Surfactants play an important role in the development of both conventional and advanced (colloidal) drug delivery systems. There are several commercial surfactants, but a proportionally small group of them is approved as pharmaceutical excipients, recognized in various pharmacopoeias and therefore widely accepted by the pharmaceutical industry.

Areas covered in this review: The review covers some of the main categories of natural, sugar-based surfactants (alkyl polyglucosides and sugar esters) as prospective pharmaceutical excipients. It provides analysis of the physicochemical characteristics of sugar-based surfactants and their possible roles in the design of conventional or advanced drug delivery systems for different routes of administration.

What the reader will gain: Summary and analysis of recent data on functionality, applied concentrations and formulation improvements produced by alkyl polyglucosides and sugar esters in different conventional and advanced delivery systems could be of interest to researchers dealing with drug formulation.

Take home message: Recent FDA certification of an alkyl polyglucoside surfactant for topical formulation presents a significant step in the process of recognition of this relatively new group of surfactants. This could trigger further research into the potential benefits of naturally derived materials in both conventional and new drug delivery systems.