Current Pharmaceutical Biotechnology - Volume 17, Issue 8, 2016

In recent years many different nanotechnology platforms have been developed for both diagnostics and cancer therapy. Researchers have been attracted to use lipid-based nanoparticles with particle size approximately 100 nm as a new pharmaceutical delivery system or pharmaceutical formulation that can be assembled from different types of lipid or other chemical components in order to overcome biological barriers. This mini-review highlights the recently published studies in the development of lipid-based nanoparticles as appropriate vehicles in cancer diagnosis and therapy with focus on their chemical structure, formulation recipes, stability, drug encapsulation, and other factors related to their formulation.

Research has been lately prospering in the field of Janus nanoparticles, focusing on new synthesis techniques and their application in various fields. This is due to the unique characteristics possessed by this type of particles such as their anisotropic nature, and their synergistic potential for combination therapy in addition to the multilevel targeting. These unique features are essential in several biomedical applications, especially the controlled drug delivery. Various techniques have been used for the synthesis of Janus nanoparticles including; masking, self-assembly, microfluidic and phase separation. They are all aiming at production of uniformly sized Janus particles with spatially separated functionalities. Herein, the main synthesis approaches of various Janus nanoparticles are briefly reviewed with the provision of examples of studies focusing on the potential applications of Janus particles in controlled drug delivery.

The oral route is the preferred mode of administration, however the poor intestinal absorption of many bioactive compounds limit their efficacy. Several strategies have been developed to overcome the low oral bioavailability of bioactive compounds. Nanocarriers present a unique opportunity to overcome this limitation due to their diverse bioactive carriage potential, surface functionality and design flexibility. Despite these favorable characteristics, the oral delivery of nanocarriers faces several challenges which are discussed in this review. The review addresses the different mechanisms of transport across the intestinal epithelium. In addition, we will comment on the various methods and models for evaluating the intestinal permeability, with a critical discussion of the uniformity of these models in investigating the oral bioavailability of nanocarrier systems. Finally, we will discuss some of the recently developed nanocarriers for oral delivery of bioactives that show promising results.

Nanomedicine has opened the way to the design of more efficient diagnostics and therapeutics. Moreover, recent literature has illustrated the use of short cationic and/or amphipathic peptides, known as cell-penetrating peptides (CPPs), for mediating advanced drug delivery. CPPs exploit their ability to enter cells and enhance the uptake of many cargoes ranging from small molecules to proteins. The distinctive properties of nanocarriers (NC) based systems provide unforeseen benefits over pure drugs for biomedical applications and constitute a challenging research field particularly focused on imaging and delivery; nonetheless, several problems have to be overcome to make them a viable option in clinic. The use of CPPs improves significantly their delivery to specific intracellular targets and thus readily contributes to their use both for effective tumor therapy and gene therapy. A key issue is related to their mechanism of uptake, because although classical CPPs enhance NCs’ uptake, the entry mechanism involves the endocytic pathway, which means that the delivered material is sequestered within vesicles and only a small amount will escape from this environment and reach the desired target. In this review, we will summarize recent advances in the use of CPP for enhanced delivery of nanocarriers, nucleic acids, and drugs, we will discuss their uptake mechanisms and we will describe novel approaches to improve endosomal escape of internalized nanosystems.

Lipid nanocapsules (LNCs) were designed more than 15 years ago to deliver lipophilic drugs to cells with non toxic excipients by mimicking lipoproteins. During the last 5 years these promising nanocarriers were re-designed to deliver nucleic acids to cancer cells. This short review sums up the features of LNCs and describes how DNAs or RNAs can be associated or encapsulated in these lipid carriers. The results of transfection effects on cells in vitro or in vivo are also presented. These new therapeutic strategies have been mainly proposed for glioma and melanoma treatment because these cancers are characterized by multiple acquired resistances, which can be reversed by DNA transfection or siRNA interference as it is discussed in this paper. In conclusion, LNCs are very good candidates to deliver nucleic acids to cells in the course of anti-cancer therapies.

RNA interference (RNAi) is an evolutionary conserved highly specific gene-silencing mechanism initiated by small interfering RNA (siRNA) molecules. Fast-paced preclinical and clinical studies helped the siRNA technology become an efficient tool for undruggable targets in different diseases including genetic diseases, viral diseases and cancer. Despite great feature of siRNAs that can down-regulate any protein in the cells, the full potential and the success of the preclinical studies could not be translated into largely successful clinical outcomes. It has become clear that the possibility of overcoming the pitfalls for in vivo siRNA therapy fully depends on delivery systems. In this review, we start with the challenges and barriers for in vivo siRNA delivery. Then we briefly discuss the recent developments in siRNA modification technology. We specifically focused on siRNA lipidation and delivery approaches with special emphasis on the lipid based hybrid systems. Here we summarize the journey of lipid-based micelle-like nanoparticle systems that combine longevity in blood, effective cellular uptake and endosomal escape for successful siRNA delivery and discuss the multifunctional stimuli-sensitive systems based on lipids as the next generation smart systems.

MicroRNAs (miRNAs) are a class of post-transcriptional gene expression modulators. In the past two decades, over 1500 human miRNAs were discovered. These small non-coding RNAs regulate various biological processes, including cell growth, proliferation, differentiation, and cell death. Thus, miRNAs have been proposed as new therapeutical agents in different multifactorial diseases such as cancer. Since miRNAs therapies represent a great promise, many research studies have been focused on the development of delivery strategies to overcome miRNAs biopharmaceutical issues. Lipid delivery systems are undoubtedly the non-viral carriers most largely investigated due to their biocompatibility, biodegradability, easy production, low toxicity and immunogenicity, possibility to easily modify the carriers for targeting strategies. In this mini-review we provide a rapid and updated overview on the lipid delivery system currently used to deliver miRNAs, pointing out the progresses achieved in the optimization of these nanovectors, which led up to the first clinical trial.