Editorial [Hot Topic: Non-Invasive Delivery of iRNAs, Proteins, Peptides, Cytokines and Nanoparticles (Guest Editor: Bingmei M. Fu)]

For non-invasive or systemic delivery of therapeutic agents or drug carriers, it is very important that these cargos can successfully cross the microvessel wall, arrive the target cells through interstitial transport, and/or penetrate the cell membrane, diffuse in the cytoplasm, and cross the nuclear envelope. Meanwhile they should be non-toxic to the healthy tissues and can survive the plasma clearance, degradation and consumption during the journey to the target cells and/or cell nuclei. In this issue of non-invasive delivery of iRNAs, proteins, peptides, cytokines and nanoparticles, recent technologies and transport models related to the drug carrier design and delivery are presented. First, Rivera and Yuan discuss “critical issues in delivery of RNAi therapeutics in vivo”. Interfering RNAs (iRNAs) are a new class of drugs for treatment of various diseases through gene regulation. To achieve their therapeutic effects, novel strategies have to be developed to enhance their stability, overcome transport barriers, and reduce immunogenicity and cytotoxicity. This review describes recent approaches and concerns in iRNA delivery in vivo. Following iRNA delivery, Wu et al., have reviewed “challenges and strategies in developing microneedle patches for transdermal delivery of protein and peptide therapeutics”. This review updates the advantages and disadvantages of a variety of newly designed microneedles including insoluble solid, soluble/degradable solid, phase-transition and hollow microneedles, which are specifically designed for non-invasive delivery of proteins and peptides across the skin. Controlled releases of growth factors and cytokines have been widely used in wound repair and tissue engineering. Peattie has thus contributed a review about “release of growth factors, cytokines and therapeutic molecules by hyaluronan-based hydrogels”. “Simple” and “Regulated” releases of these molecules by modified forms of hyaluronan have been presented for the therapeutic, clinical, veterinary and laboratory applications. This decade has been marked the rapid development of nanoparticles for therapeutic and diagnostic purposes. Many progresses have been achieved in drug delivery using nanoparticles, especially in solid tumor treatment. Bhagat et al., have reviewed “nanocarriers to solid tumors: considerations on tumor penetration and exposure of tumor cells to therapeutic agents”. Their review describes a variety of rational designs of self-assembling nanocarriers, e.g., liposomes and micelles, for achieving adequate tumor penetration and lethal doses to all cancer cells of a solid tumor but minimizing normal organ toxicities. To increase the treatment efficacy and reduce side effects, multiple drugs can be co-delivered to the tumor. Choudhury and He have thus contributed a review for “nanocarriers for the simultaneous co-delivery of therapeutic genes and anticancer drugs”, which summarizes novel strategies that can simultaneously load genes and chemical drugs on the same nanoparticles but release these cargos at specific times. More and more men and women suffer from Alzheimer's and Parkinson's diseases and other brain disorders when they are aging. Many therapeutic drugs for these central nervous diseases have been developed but their applications are limited by their delivery to the brain, particularly by the blood-brain barrier (BBB) if they are delivered through systemic administration. In the review by Konofagou et al., they have demonstrated a novel brain drug delivery through “ultrasound-induced blood-brain barrier opening”. A controllable focused ultrasound, in conjunction with microbubbles, is the effective technique that can induce localized BBB opening non-invasively and regionally. In addition to ultrasound-induced BBB opening, in “experimental methods and transport models for drug delivery across the blood-brain barrier”, Fu has suggested other delivery strategies across the BBB based on the quantitative experimental approaches and transport models for the BBB permeability to water, ions, and solutes including nutrients, therapeutic agents and drug carriers. Finally, in “pharmacokinetics/pharmacodynamics model-supported early drug development”, Chen et al., have discussed how pharmacokinetic pharmacodynamic (PK/PD) modeling and simulation (M&S), which offer quantitative assessment of exposure- response relationships, contribute to the drug development and regulatory decisions in pharmaceutical industry.