Current Drug Metabolism - Volume 13, Issue 4, 2012

In recent years, nanoscale drug delivery systems (NDDS) have been transformed from laboratory to market with faster speed due to the combination of nanotechnology, material science and life science. Advances in designing and engineering of NDDS with distinct physical and biochemical properties will bring enormous impact on public health because NDDS are capable of carrying drugs (small, peptides, proteins), nucleic acids or antigens across biological barriers to reach a specific organization and then locate in the cell or even sub-cellular organelles, which can help to improve treatment efficacy and reduce adverse drug reactions. Global research into targeting of drugs, biologics and diagnostic agents via intravenous and interstitial routes of administration with NDDS is accelerating dramatically. However, more and more researchers come to realize that the biosafety and the biological performance of NDDS should be made clear, which are often related with the dose, size, shape, surface reactivity and inherent material properties of NDDS. Indeed, the underlying processes of toxicity are both complex and multifaceted, and in need of urgent detailed cell and molecular investigation. In this emerging area, many advances have been made in the recent years, but no latest books or edited collections have well summarized the recent advances. This special issue will be the first one to summarize the latest progress, which is of great appeal to students and researchers in the fields of biomedical engineering, nanotechnology, materials science, physics, medicine and biology. It is also of interest to practising engineers, materials scientists, chemists and research medical doctors involved in the development of more safety NDDS for medical care. Particularly, the issue will play a key role on professional reference and future teaching.

Micelles assembled from amphiphilic poly(ethylene glycol)/poly(ε-caprolactone) (PEG/PCL) copolymers are promised as safe and effective drug delivery systems. They offer the potential to achieve high solubility of hydrophobic drugs, long blood circulation time and effective delivery to target organs. These advantages contribute to their application as vehicles of a broad variation of therapeutic compounds. In this review, we discussed the safety of the copolymers, release behavior of PEG/PCL micelles in vitro, and pharmacokinetic profiles referring to the optimized fate in vascular system and targeting biodistribution.

Nanomaterials have unique physicochemical properties compared with those bulk materials of the same composition. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. A number of studies on the effects of Nanomaterials in vitro and in vivo systems have been published. However, while the number of nanomaterials types and applications continues to increase, studies to characterize their effects after exposure and to address their potential toxicity are few in comparison, there is still a need for further studies that conclusively establish their safety/toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable. The major goal of this review is to summarize 1) analytical techniques applied for characterization of nanomaterials, 2 current analytical methods to assess nanomaterials toxicity in vitro and in vivo; 3) research progress of polymeric nanomaterials toxicity; 4) outlook.

Chitosan is a natural polysaccharide which is generally biodegradable, biocompatible and mucoadhesive, thus, attracting considerable interest of scientific researchers. The application of chitosan as nanocarriers for drug delivery thrived. And some of their pharmacokinetics and biodistribution profiles were studied, which are crucial to develop a promising drug delivery system. In this article, we will first give an introduction for the chitosan as drug delivery system, especially as nanoparticles. Then, we focus on pharmacokinetics studies of various chitosan nanoparticles both in vitro and in vivo. In a following part, we refer to researches on biodistribution properties of chitosan nanoparticles. Here we crucially discuss the in vivo fate of chitosan nanoparticles. And finally, toxicity issue is discussed and conclusions are drawn.

Due to great efforts in past 45 years, several liposomal products including two liposomal vaccine products have been commercialized and many more potential products are now under clinical trial stage. Although liposome has significantly reduced the toxicity of the drugs with improved or maintained the efficacy, its further development has been limited by its instabilities during preparation and storage, incompatibility with certain drugs, relative high cost of production and quality control as well as unspecified drug release time and sites in vivo. In vivo behaviors of liposomal drugs highly depend on their physiochemical properties including lipid composition, particle size, surface charge, surface modifications and the administrated dose as well as the route of administration. Based on the literature reports from the past two decades, the current review provided an updated summary of the key factors in liposomal preparations for clinical usage and its impact on the alternation of pharmacokinetic and disposition behaviors of drugs encapsulated in the liposome formulations. Clinical applications of liposomal preparation in anti-tumor agents, anti-infective agents as well as the macromolecules have been highlighted.

Nanoemulsions are composed of nanoscale droplets of one immiscible liquid dispersed within another, which have been the focus of extensive research worldwide due to their solubilization and transportation capacity of both hydrophobic and hydrophilic active compounds with unique physical properties. In a broad sense, submicron-emulsion, microemulsion, self-microemulsifing drug delivery system, lipid emulsion and cholesterol-rich microemulsion (LDE) all belong to nanoemulsions. The review starts with a brief introduction to the definition, formulation rationale, and types of nanoemulaions, and focused on, by different administration routes such as the oral, intravenous, transdermal, ocular nasal and rectal routes, the absorption, disposition, pharmacokinetics properties of nanoemulsions.

Solid lipid nanoparticles (SLNs) are primarily composed of solid lipids, which thus impart to them some of the fundamental properties of these lipids, including biocompatibility, biodegradability and low-toxicity. SLNs represent a unique class of colloidal drug delivery systems that possess the advantages of both the “soft” drug carriers such as emulsions and liposomes and polymeric nanoparticles. In this review, we will provide an overview on the absorption, disposition and pharmacokinetics of SLNs. The lipidic nature, as well as the relatively small particle size, of SLNs ensures sufficient affinity with the biomembranes, and results in improved absorption by either of the oral, transdermal, pulmonary, nasal, ocular, rectal or buccal route. One special aspect of oral SLNs is the enhanced lymphatic absorption by either the chylomicron-association pathway or the M cell uptaking pathway. Intravenous SLNs are predominantly uptaken by the liver or spleen following opsonization by the complementary system. Modification of SLN surface with PEGs chains will mask the hydrophobic surface and divert SLNs to non-hepatic and non-splenic organs, while ligand-modification will achieve active targeting to specific tissues or organs. Degradation of SLNs is primarily based on the degradation of the lipids themselves by lipase. Pharmacokinetics reflects the effect of the lipidic vehicles of SLNs on in vivo disposition of the loaded drugs.

Nowadays, biodegradable nanoscale preparations such as liposomes, micelles, nanoparticles (NPs), and solid lipid nanoparticles (SLN) have attracted increasing attention from major researchers. This article aims to review the absorption, pharmacokinetics, distribution properties and toxicity of the above-mentioned nanoscale preparations and the relative methodology. It may be significant for successful use of more nanoscale preparations in clinical practice.

Nowadays, biodegradable nanoscale preparations such as liposomes, micelles, nanoparticles (NPs), and solid lipid nanoparticles (SLN) have attracted increasing attention from major researchers. Meanwhile the biosafety of the nanomaterials brings more and more attention. Toxicity of the biodegradable nanoscle preparations varies depending on their particle size, shape, surface structure, et al. This article aims to review the toxicity of the above-mentioned nanoscale preparations and the relative methodology. It may be significant for successful use of more nanoscale preparations in clinical practice.

In recent years, many researchers have paid more and more attentions on the use of Nanotechnology. Solid lipid nanoparticles (SLNs) are emerged as a promising alternation herein to emulsions, liposomes, microparticles and polymeric nanoparticles for their advantages. As promising drug carrier systems, SLNs are valuable for nanomedicine and have been widely used as delivery systems mostly for drugs and macromolecules like proteins, oligonucleotides and DNA by various application routes, such as intravenous, oral, duodenalous, intramuscular, pulmonary, intranasal, ocular, rectal and intraperitoneal administrations. It has been shown that SLNs can increase bioavailability, alter pharmacokinetic parameters and tissue distribution of the drug loaded. In this review, we will primarily focus on the absorption, pharmacokinetics and disposition properties of SLNs for their possible applications in drug delivery.

The renewed interest in inhalation delivery over recent years has led to an expansion in the understanding of lung pharmacokinetics. Historically optimisation of inhaled drugs focused largely on development of material properties, consistent with achieving a good lung deposition, alongside demonstrating appropriate in vivo efficacy with little understanding of the relationship to pharmacokinetics in the lung. Recent efforts have led to an increased understanding of lung concentrations and how to maximise exposure in order to achieve the desired pharmacological response at a dose consistent with development of an inhaled product. Although there is a prerequisite for excellent potency in inhalation delivery, it is essential that this be combined with pharmacokinetic properties that allow sufficient free concentration at the effect site in lung to exert the pharmacological response for an appropriate dosing interval. Increases in basicity, polarity and/or decreases in aqueous solubility can extend pharmacokinetic duration and assist in finding the right balance between lung and systemic exposure. Current evidence suggests there are similarities in lung retention in rat and dog and that animal lung concentration data can enable pharmacokinetic-pharmacodynamic relationships to be derived thus providing more confidence in the requirements for man. Although inhaled delivery is challenging from a pharmacokinetic point of view, direct evaluation of exposure in the target organ has enabled further understanding of the drivers for drug disposition and highlighted the need for further development of predictive lung pharmacokinetic tools in the future.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in pregnancy to treat fever, pain and inflammation. Indications for chronic use of these agents during pregnancy are inflammatory bowel or chronic rheumatic diseases. Since the seventies, NSAIDs have been used as effective tocolytic agents: indomethacin has been the reference drug, delaying delivery for at least 48 hours and up to 7-10 days. Additionally, self-medication with NSAIDs is practiced by pregnant women. NSAIDs given to pregnant women cross the placenta and may cause embryo-fetal and neonatal adverse effects, depending on the type of agent, the dose and duration of therapy, the period of gestation, and the time elapsed between maternal NSAID administration and delivery. These effects derive from the action mechanisms of NSAIDs (mainly inhibition of prostanoid activity) and from the physiological changes in drug pharmacokinetics occurring during pregnancy. Increased risks of miscarriage and malformations are associated with NSAID use in early pregnancy. Conversely, exposure to NSAIDs after 30 weeks' gestation is associated with an increased risk of premature closure of the fetal ductus arteriosus and oligohydramnios. Fetal and neonatal adverse effects affecting the brain, kidney, lung, skeleton, gastrointestinal tract and cardiovascular system have also been reported after prenatal exposure to NSAIDs. NSAIDs should be given in pregnancy only if the maternal benefits outweigh the potential fetal risks, at the lowest effective dose and for the shortest duration possible.