Parameters and Strategies to Overcome Barriers to Systemic Delivery
In the preceding chapter, the possibilities to couple experiments with computation techniques to characterize and optimize the performance of a drug delivery system have been described. In fact, while it is important to address the problems with the physi
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Parameters and Strategies to Overcome Barriers to Systemic Delivery Radhika Narayanaswamy, Sara Aly Attia, and Vladimir P. Torchilin
Abstract In the preceding chapter, the possibilities to couple experiments with computation techniques to characterize and optimize the performance of a drug delivery system have been described. In fact, while it is important to address the problems with the physical properties of a drug delivery system for optimal delivery performance, the impact of the physiological, bio-chemical and chemical barriers within the biological system on the efficiency of systemic drug delivery should not be overlooked, either. Keeping this in mind, in this chapter we will give an overview of the various physiological, chemical and bio-chemical barriers in systemic drug delivery, using oral drug delivery route as an example. We will also discuss the challenges in drug delivery to specific targets such as solid tumors and brain since these targets pose unique barriers that need specific knowledge on to tweak them suitably for enhanced drug delivery and achieve therapeutic benefit for several lifethreatening illnesses and incurable disorders. It is hoped that, with more awareness of the various barriers in systemic drug delivery and any issue with the drug property, potential losses of therapeutics in a biological body can be minimized and the efficiency of therapies can be increased at the clinical level. Keywords Barriers · Nanotechnology · Tumor targeting · Brain · Systemic delivery
18.1 Introduction The process of drug discovery and development is quite expensive and divided into several stages. These include identification of a target, finding hits by screening millions of compounds (candidates with desirable interaction with the target) and identifying the leads with optimized activity suitable for testing in pharmacological models. Further optimization of bio-pharmaceutical properties can generate the R. Narayanaswamy · S. A. Attia · V. P. Torchilin (B) Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA e-mail: [email protected] © Springer Nature Switzerland AG 2020 W.-F. Lai (ed.), Systemic Delivery Technologies in Anti-Aging Medicine: Methods and Applications, Healthy Ageing and Longevity 13, https://doi.org/10.1007/978-3-030-54490-4_19
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drug-like compounds (drug candidates) selected for further development. The whole process starts with screening of ~10,000 compounds that tapers down to very few compounds suitable for further development. Only a very small percentage of the drug candidates find success in clinical testing owing to poor pharmacokinetic properties, lack of clinical efficacy, toxicity, adverse drug effects and a small percent because of commercial limitations. This failure is not preferred by pharmaceutical companies and the health care industry since it is clear that this is not due to the lack of biological activity or target interaction in vitro. It is important to evaluate several other
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