ABSTRACT
Keywords: nanomedicine, topical delivery, dermal and transdermal delivery, gene therapy, non-viral vectors, gemini-lipid nanoparticles, biphasic vesicles, transfersomes, niosomes, plasmid, nucleic acid, skin, liposomes, pharmaceutics, nanocarrier, needle-free, non-invasive, administration route 31.1 IntroductionHuman diseases associated with genetic mutations can be treated by the introduction of a vector encoding a healthy gene, by using a therapeutic DNA/RNA construct to enhance gene expression, or to inhibit production of deleterious proteins (e.g., oncoproteins). Thus, the delivery of intracellular nucleic acid-based drugs can be exploited for vaccination and for the treatment of several diseases
such as cancer, viral infections and, dermatological diseases [1-4]. Many nucleic acid-based therapeutics (e.g., plasmid DNA (pDNA), antisense oligonucleotides (AON) and small interfering RNA (siRNA)) have either been approved or in different phases of clinical trials [5-8]. However, the clinical outcome of the different gene therapies is still unsatisfactory. Gene delivery is hindered by the rapid extra-and intracellular enzymatic degradation, thereby reducing the amount that is available in the host to elicit the response. The cellular uptake of these genetic products is usually very low due to their high molecular weights and anionic nature. After cellular entry, nucleic acids can be degraded in the endosomal/lysosomal compartments. The small fraction that may escape from the endosomes/lysosomes is exposed to cytoplasmic degradation. In addition, the nuclear membrane represents an additional barrier for gene transcription, when using pDNA. Moreover, an additional barrier exists for topical gene delivery; the limited penetration through the stratum corneum (SC), the outermost layer of the skin and the most recognized barrier for dermal and transdermal delivery of drugs, proteins and nucleic acids.Many delivery systems have been developed to overcome the barriers associated with the use of genetic materials. However, most of these vectors (either viral or non-viral) are usually delivered parenterally, through different administration routes, such as, intravenous, intramuscular, subcutaneous, intradermal, and epidermal injections. These methods involve piercing the skin and most likely the underlying tissues. Due to the invasiveness of these methods, topical administration could be a very attractive and non-invasive gene therapy approach. Liposomes were among the first vehicles that have been used for topical gene delivery. Although liposomes were considered as a promising approach, recent reports have shown that liposomes made solely from phospholipids may not be able to penetrate deep into the dermal skin layers [9, 10]. Hence, other liposomal compositions or nanoparticles (e.g., transfersomes, ethosomes, niosomes, nanoemulsions, gemini-lipid nanoparticles, and biphasic vesicles) have been developed to enhance penetration through the SC. This chapter focuses on the recent advances in engineering non-invasive (i.e., non-injectable), non-viral nanovectors for dermal/transdermal delivery of different genetic materials and on their future prospects.
