Nanostructures for oral delivery of therapeutic nucleic acids (original) (raw)
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Nucleic acid (NA) therapy has gained importance over the past decade due to its high degree of selectivity and minimal toxic effects over conventional drugs. Currently, intravenous (IV) or intramuscular (IM) formulations constitute majority of the marketed formulations containing nucleic acids. However, oral administration is traditionally preferred due to ease of administration as well as higher patient compliance. To leverage the benefits of oral delivery for NA therapy, the NA of interest must be delivered to the target site avoiding all degrading and inhibiting factors during its transition through the gastrointestinal tract. The oral route presents myriad of challenges to NA delivery, making formulation development challenging. Researchers in the last few decades have formulated various delivery systems to overcome such challenges and several reviews summarize and discuss these strategies in detail. However, there is a need to differentiate between the approaches based on target so that in future, delivery strategies can be developed according to the goal of the study and for efficient delivery to the desired site. The goal of this review is to summarize the mechanisms for target specific delivery, list and discuss the formulation strategies used for oral delivery of NA therapies and delineate the similarities and differences between local and systemic targeting oral delivery systems and current challenges.
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The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference and aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affinity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cel...
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Nucleic acids (NA) therapies, including therapy with genes, aptamers or antisense oligonucleotides, have been showing promising results, especially in the treatment of severe diseases (e.g. cancer and AIDS). Nevertheless, the full success of medical treatments requires efficient achievement of the therapeutic target and also the safety and effectiveness of the pharmaceutical system. NA are not very efficient when administered alone, which means that the use of appropriate methods for in vivo transfection of these molecules into targeted cells is fundamental. Examples of these techniques are the use of viral and non-viral vectors to transfer the NA to the cells nucleus. Despite viral vectors have been demonstrating superior effectiveness for NA transfer, some drawbacks have been pointed out, which focused the research in the non-viral vectors. However, the development of effective NA delivery systems remains a challenge for pharmaceutical technologists, mainly because of their in vivo failure, which hinders their clinical application. In this review article we address the characteristics of NA molecules and their respective limitations for formulation and administration. An update on the state of the art related to the latest and outstanding developments from the in vivo applications of NA viral and non-viral delivery systems is also presented. From this review, we can conclude that there is a lack of research regarding pre-clinical studies in specific animal models of disease, which is required for further human clinical trials and for their use in clinics.
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Nucleic acids have gained significant interest in medicine for their therapeutic and prophylactic application. However, if delivered alone, nucleic acids are susceptible to nuclease degradation. Hence, delivering them with a suitable delivery system which can protect them could be beneficial. There is an increasing demand for novel delivery systems for nucleic acids to use them as vaccines and for gene therapy. Out of many types of delivery systems, nanoparticles are gaining importance because of their suitable properties. Hence, this chapter mainly focuses on discussing various types of nanoparticles for the delivery of nucleic acids. Recent applications of various types of nanoparticle-based viral and non-viral vectors and their advantages and disadvantages will be discussed in detail. The potential improvements which can be made to each existing nanoparticle systems are expressed. Overall this chapter is to provide an overview of importance of nanoparticles for nucleic acid deliv...
Nonviral Approach for Targeted Nucleic Acid Delivery
Despite their relatively lower efficiency, nonviral approaches are emerging as safer alternatives in gene therapy to viral vectors. Delivery of nucleic acids to the target site is an important factor for effective gene expression (plasmid DNA) or knockdown (siRNA) with minimal side effects. Direct deposition at the target site by physical methods, including ultrasound, electroporation and gene gun, is one approach for local delivery. For less accessible sites, the development of carriers that can home into the target tissue is required. Cationic peptides, lipoplexes, polyplexes and nanoplexes have been used as carriers for delivery of nucleic acids. Targeting ligands, such as cell targeting peptides, have also been applied to decorate delivery vehicles in order to enhance their efficacy. This review focuses on delivery strategies and recent progress in non-viral carriers and their modifications to improve their performance in targeting and transfection.
Nucleic acid therapies involving DNA or RNA have significant potential to treat genetic disorders, infectious diseases, and cancer; however, research suggests that less than 1% of injected nucleic acid doses reach target cells in an active form. [34] Meanwhile, the application is in its infancy, and its clinical application still has a long way to go, needing an in-depth understanding of the characteristic of NCNAs for the exploration of higher precision, fully controllable nanocarriers. [33] "With proper and more predictive in vitro assays, the preclinical pipeline will become more efficient, faster, and economic.