Journal of Pharmaceutical Investigation最新文献

Background: Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system. With its minimal invasiveness, microneedle can deliver nucleic acid drugs with enhanced efficacy and improved stability.

Area covered: This review describes nucleic acid medicines' current state and features and their delivery systems utilizing non-viral vectors and physical delivery systems. In addition, different types of microneedle delivery systems and their properties are briefly reviewed. Furthermore, recent advances of microneedle-based nucleic acid drugs, including featured vaccination applications, are described.

Expert opinion: Nucleic acid drugs have shown significant potential beyond the limitation of conventional small molecules, and the current COVID-19 pandemic highlights the importance of nucleic acid therapies as a novel vaccination platform. Microneedle-mediated nucleic acid drug delivery is a potential platform for less invasive nucleic acid drug delivery. Microneedle system can show enhanced efficacy, stability, and improved patient convenience through self-administration with less pain.

Background: Numerous drug delivery strategies have been studied, but many hurdles exist in drug delivery rates to the target site. Recently, researchers have attempted to remotely control the in vivo behavior of drugs with light to overcome the shortcomings of conventional drug delivery systems. Photodynamic and photothermal systems are representative strategies wherein a photosensitive material is activated in response to a specific wavelength of light.

Area covered: Photosensitive materials generally exhibit poor solubility and low biocompatibility. Additionally, their low photostability negatively affects delivery performance. A formulation of lipid-based nanoparticles containing photosensitive substances can help achieve photosensitive drug delivery with improved biocompatibility. The lipid bilayer structure, which can be assembled and disassembled by modulating the surrounding conditions (temperature, pH, etc.), can also be crucial for controlled release of drugs.

Expert opinion: To the best of our knowledge, translation research on photoresponsive nanoparticles is scarce. However, as various drugs based on lipid nanoparticles have been clinically approved, the development potential of the lipid-based photoresponsive nanoparticles seems high. Thus, the identification of valid indications and development of optimum medical devices will increase the interest in photoresponsive material-based nanoparticles.

Background: Currently nanomedicines are the focus of attention from researchers and clinicians because of the successes of lipid-nanoparticles-based COVID-19 vaccines. Nanoparticles improve existing treatments by providing a number of advantages including protection of cargo molecules from external stresses, delivery of drugs to target tissues, and sustained drug release. To prevent premature release-related side effects, stable drug loading in nanoformulations is required, but the increased stability of the formulation could also lead to a poor drug-release profile at the target sites. Thus, researchers have exploited differences in a range of properties (e.g., enzyme levels, pH, levels of reduced glutathione, and reactive oxygen species) between non-target and target sites for site-specific release of drugs. Among these environmental stimuli, pH gradients have been widely used to design novel, responsive nanoparticles.

Area covered: In this review, we assess drug delivery based on pH-responsive nanoparticles at the levels of tissues (tumor microenvironment, pH ~ 6.5) and of intracellular compartments (endosome and lysosome, pH 4.5-6.5). Upon exposure to these pH stimuli, pH-responsive nanoparticles respond with physicochemical changes to their material structure and surface characteristics. These changes include swelling, dissociation, or surface charge switching, in a manner that favors drug release at the target site (the tumor microenvironment region and the cytosol followed by endosomal escape) rather than the surrounding tissues.

Expert opinion: Lastly, we consider the challenges involved in the development of pH-responsive nanomedicines.