Building nanostructures with drugs

Abstract

The convergence of nanoscience and drug delivery has prompted the formation of the field of nanomedicine, one that exploits the novel physicochemical and biological properties of nanostructures for improved medical treatments and reduced side effects. Until recently, this nanostructure-mediated strategy considered the drug to be solely a biologically active compound to be delivered, and its potential as a molecular building unit remained largely unexplored. A growing trend within nanomedicine has been the use of drug molecules to build well-defined nanostructures of various sizes and shapes. This strategy allows for the creation of self-delivering supramolecular nanomedicines containing a high and fixed drug content. Through rational design of the number and type of the drug incorporated, the resulting nanostructures can be tailored to assume various morphologies (e.g. nanospheres, rods, nanofibers, or nanotubes) for a particular mode of administration such as systemic, topical, and local delivery. This review covers the recent advances in this rapidly developing field, with the aim of providing an in-depth evaluation of the exciting opportunities that this new field could create to improve the current clinical practice of nanomedicine.

Peptide–drug conjugates as effective prodrug strategies for targeted delivery

“…For instance, the use of Kolliphor EL (formerly Cremophor EL) to “solubilize” paclitaxel (Taxol ® ) as an emulsion has been associated with allergic reactions and peripheral neuropathy, among other side effects [38]. Conjugating the anticancer drug to a hydrophilic peptide can alleviate this solubility problem and provides the opportunity for the inclusion of greater functionality [31]. In this section, we will illustrate two commonly utilized peptide types that can enhance drug delivery—integrin-targeting and cell-penetrating peptides—and discuss the application of water-soluble PDCs for theranostic applications.…”

“…1) [14, 31]. In this novel design, the PDCs essentially form their own drug delivery vehicle (namely one-component nanomedicines), one that is capable of breaking down, either over time or due to some specific stimulus, and releasing the active drug.…”

Self-assembling prodrugs

“…The release of the drug from the nanostructure is a key feature in the efficacy of the drug conjugate and it can be strongly influenced by the stability and the network features of the hydrogel. 178 In in vivo settings, such as a resection cavity, 179 the hydrogel may be subject to three-dimensional shear and strain stresses that could compromise its integrity thus leading to unexpected drug release profiles. Subsequent increased exposure of the drug conjugate caused by hydrogel breakdown can facilitate faster and unpredictable drug release.…”

“…Furthermore, some concerns have been raised with regard to the long-term stability of the nanostructures formed, particularly upon introduction to the in vivo physiological environment. 178 …”

Protease-Sensitive Nanomaterials for Cancer Therapeutics and Imaging

“…16,33,40,41,44,64,65 Incorporation of protease sensitivity can further improve selectivity to tumor tissue and mitigate harmful side effects to healthy tissues. 66−69 Of particular interest are the following proteases whose abnormal activity is associated with cancer: cathepsins, matrix metalloproteinases, and urokinase-type plasminogen activators.…”