Nanocarrier-based topical drug delivery for the treatment of skin diseases

Introduction: Skin disorders will continue to cause complications in patients. At present, there is an expansion of research into dermatologic treatment due to a critical need for new treatment options to treat skin diseases.

Areas covered: The skin itself provides a natural barrier against particle penetration for topical delivery. However, it also offers a potential approach for the delivery of therapeutics, especially in diseased skin and via the openings of hair follicles. Recent innovation might be achieved in the field of dermatological treatment with improvement in the dermal localization of bioactives into the affected skin region, via novel nanocarriers that deliver the drugs directly to the target cells. After application, these nanocarriers can penetrate through the stratum corneum into viable skin and accumulate at the target site. However, noteworthy uptake does occur after damage and in certain diseased skin.

Expert opinion: Skin-targeted topical delivery by means of nanosystems, in order to produce sustained release and maintain a localized effect, will result in an effective treatment of various life-threatening dermatological conditions. In addition, research continues into the interactions between novel particles, skin and skin lipid, and the influence of particle composition on drug distribution within the skin strata.     

Core–shell nanocarriers for cancer therapy. Part I: biologically oriented design rules

Introduction: The application of nanotechnologies to the cancer field for therapeutic, imaging or diagnostic purposes represents an advanced and very attractive approach to overcome the main limits related to conventional chemotherapy. In particular, core–shell nanocarriers can be engineered to provide adequate features to overcome the main biological barriers encountered by free anti-cancer drugs.

Areas covered: This review will try to summarise the design rules – as dictated by biological requirements – to take into account for proper nanocarrier design and to highlight the potential of administration routes other than intravenous.

Expert opinion: Although intravenous injection remains the most investigated route of administration for ‘nanoncologicals', research interest towards less explored administration routes allowing localised chemotherapy or delivery in close proximity to the tumour site might change the way cancer is treated in the near future. Nevertheless, an experimental set-up more biologically oriented taking into account an in-depth evaluation of stability in complex media, protein interaction, and cell interaction of novel nanoconstructs could allow their successful translation in pre-clinical and clinical settings.     

Use of nanotechnology for improved pharmacokinetics and activity of immunogenic cell death inducers used in cancer chemotherapy

Introduction: Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers.

Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology.

Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.     

Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs

Introduction: Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo.

Areas covered: In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed.

Expert opinion: During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.     

Stealth properties of poly(ethylene oxide)-based triblock copolymer micelles: a prerequisite for a pH-triggered targeting system

Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(ε-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment.     

Post‐Assembly of Oxidation‐Responsive Amphiphilic Triblock Polymer Containing a Single Diselenide

Linear amphiphilic triblock polymers containing a single diselenide (SeSe‐tri‐ABP) are synthesized by coupling reactions. They self‐assemble into spherical micelles 1 in aqueous solution. A remarkable morphology transformation of the micelles is confirmed through dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release behavior of a model molecule, Rhodamine B (RB), is studied by UV–vis spectrophotometry. It is found that post‐assembly from micelles 1 to micelles 2 is induced by the oxidation‐responsive cleavage of the diselenide group in the oxidation solution. Interestingly, the RB release studies reveal that these micelles release RB in a diphasic pattern (slow after initial fast release) within 24 h under an oxidative environment. In contrast, minimal drug release (<20%) is observed within 24 h for SeSe‐tri‐ABP micelles under aqueous conditions. Meanwhile, this release behavior of the RB‐loaded micelles can be tuned by the post‐assembly of oxidation‐responsive SeSe‐tri‐ABP in different oxidation conditions, providing a promising platform for controlled delivery of nanocarriers.

     

叶酸和聚乙二醇双修饰的壳聚糖纳米粒的制备及其性能表征

目的 利用离子交联和化学交联相结合的方法制备壳聚糖纳米粒子(NPs),并对NPs分别进行了叶酸(FA)和聚乙二醇(PEG)的修饰。方法 通过红外光谱进行结构验证;用扫描电镜和粒度分析仪对粒子的微观形态、粒径、电位等进行了表征;通过与Hela细胞摄取实验对其靶向作用进行验证。结果 离子交联和化学交联相结合的方法制备壳聚糖纳米粒子粒径在200 nm左右并且粒径分布窄,修饰后的NPs(FA-NPs、PEG-NPs及FA+PEG-NPs)粒径不受功能基团修饰的影响。激光共聚焦试验证明FA-NPs及FA+PEG-NPs能显著提高细胞对粒子的摄取,而PEG-NPs则明显降低其对粒子的摄取。结论 FA+PEG-NPs有望成为一种新型的药物载体,用于抗癌药物对癌细胞的主动靶向。     

Stability study of sodium colistimethate-loaded lipid nanoparticles

In the last decades, the encapsulation of antibiotics into nanoparticulate carriers has gained increasing attention for the treatment of infectious diseases. Sodium colistimethate-loaded solid lipid nanoparticles (Colist-SLNs) and nanostructured lipid carriers (Colist-NLCs) were designed aiming to treat the pulmonary infection associated to cystic fibrosis patients. The nanoparticles were freeze-dried using trehalose as cryoprotectant. The stability of both nanoparticles was analysed over one year according to the International Conference of Harmonisation (ICH) guidelines by determining the minimum inhibitory concentration (MIC) against clinically isolated Pseudomonas aeruginosa strains and by studying their physico-chemical characteristics. The results showed that Colist-SLNs lost their antimicrobial activity at the third month; on the contrary, the antibacterial activity of Colist-NLCs was maintained throughout the study within an adequate range (MIC ≤16?μg/mL). In addition, Colist-NLCs exhibited suitable physico-chemical properties at 5?°C and 25?°C/60% relative humidity over one year. Altogether, Colist-NLCs proved to have better stability than Colist-SLNs.     

Recent advances on biocompatible and biodegradable nanoparticles as gene carriers

ABSTRACT

Introduction: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non-viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced.

Areas covered: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes.

Expert opinion: Biocompatible and biodegradable polymers will play a necessary and important role in developing new and safe carriers for oligonucleotide delivery. More working and the development of optimized polymers will reveal more their efficacy in the treatment of patients via helping in better gene therapy.     

Micro- and nanocarrier-mediated lung targeting

Importance of the field: Drug delivery to lungs appears to be an attractive proposition on account of the large surface area of the alveolar region; it provides tremendous opportunities to improve drug therapies both systemically and locally using new drug delivery systems. Administration of drugs directly to the lungs is the most appropriate route in the treatment of asthma and other pulmonary diseases such as tuberculosis, chronic obstructive pulmonary disease and lung cancer.

Areas covered in this review: This review focuses on the utilization of nano- and microcarriers such as microspheres, nanoparticles, liposomes, niosomes and dendrimers for targeted delivery of bioactive molecules to lungs.

What the reader will gain: This review sheds light on the current status of nano- and microcarrier-mediated lung targeting of bioactive compounds.

Take home message: The literature review shows that carriers could supplement sustained drug delivery to the lungs, extended duration of action, reduced therapeutic dose, improved patient compliance, and reduced adverse effects of highly toxic drugs. There is still a need to identify more specific receptors that are present exclusively in the lungs. The identification of such receptors may also facilitate drug targeting to further specific parts of the lungs, such as bronchioles and alveoli.