ABSTRACT
Keywords: drug carriers, small molecules, biopharmaceuticals, translation, technical and regulatory challenges
to as nanomedicine. Nanomedicine comprises all applications of nanotechnology in diagnosis, prevention and treatment of diseases, including also technical approaches or nano-machines such as pacemakers, biochips, hearing aids, and medical flow sensors. To be more specific we have chosen the word nano-pharmaceuticals for the purpose of this chapter. Herein we discuss the potential of carriers in the sub-micron dimension for advanced drug delivery.Physical and chemical properties, in particular solubility, permeability and chemical/biological stability are factors that may limit the bioavailability of a drug and consequently also the use in medicine/clinics. Highly potent actives can be discarded or delayed for such reasons. In general drugs can be classified in two groups, which also distinguish them in their degree of dependency on delivery systems. On the one hand there are chemically manufactured small molecules and on the other hand the so called biopharmaceuticals, which are macromolecules generated by means of biotechnological methods. Biopharmaceuticals comprise mainly protein and peptide drugs as well as nucleotide drugs. In case of small molecules, medicinal chemistry approaches sometimes can improve properties such as solubility, stability toward metabolic degradation or reduced toxicity in order to create more efficient agents. In cases where this is not possible formulations are needed to achieve efficient and safe pharmaceuticals. The term “drug delivery” implies a rather complicated process where the right concentration in time has to be achieved at the target location, ideally even with high specificity. In particular anti cancer drugs may benefit from targeted carriers to minimize the adverse effects in healthy tissue and maximize toxicity for cancer cells. In contrast, for biopharmaceuticals a delivery system is always required since their shared properties are large molecule size, structural complexity and fast metabolism. All these features hinder the achievement of sufficing bioavailability of the “naked” molecule. Biopharmaceuticals with their huge diversity however, are believed to realize personalized medicine to treat complex diseases with variable origin. But these new and highly promising drug candidates, originating from the enormous progress in genetics and biotechnology, are absolutely reliant on adequate delivery systems and technologies to exploit their therapeutic
potential. In this regard medicine and pharmaceutical industry’s hopes are pinned on the emerging science of nanotechnology.This chapter provides an overview on currently investigated or unmet therapeutic needs, which could be opportunities for nanoscale delivery systems, summarize in brief the current arsenal of nanocarrier technologies and their ongoing translation into the clinics. Finally we discuss the challenges for developing future nanopharmaceuticals. 12.2 Therapeutic Needs and Opportunities for
12.2.1 Delivery of Small-Molecule Drugs A well-designed drug delivery system may be of advantage even for established drugs (i.e., small molecules) because it can improve the therapeutic index, for example, by altering the pharmacokinetic and the body distribution [1]. For other actives a safe and efficient application without delivery system may even be impossible. The delivery systems used cover a wide range of materials and structural complexity. Within this chapter we mainly discuss nanoparticulate approaches. The optimal delivery system varies with the physicochemical and pharmacological properties of the active. Pharmaceutical industry prefers oral administration, but this route is limited for actives with sufficient water solubility, a reasonable up-take rate through the intestinal epithelium and limited deg radation in the intestinal milieu. A very frequent problem is the poor water solubility. This problem can be overcome by comparatively simple approaches. NanoCrystal® technology developed by Elan Drug Technologies, for example, refers to nanoparticles made from pure active by a proprietary process for size reduction and stabili zation. The solubility is increased due to the enormously enlarged surface. Another approach also referred to as nanomedicine is to add a polymeric tag to the active (polymer-prodrugs) to improve the solubility or disposition in the body [2]. Estimations on drug devel opment state that 70% of new molecular entities in industrial candi date pipelines suffer from low water solubility [3].
