Challenges and opportunities in the advancement of nanomedicines

Abstract

Nanomedicine-based approaches to cancer treatment face several challenges that differ from those encountered by conventional medicines during clinical development. A systematic exploration of these issues has led us to identify the following needs and opportunities for further development: (1) robust and general methods for the accurate characterization of nanoparticle size, shape, and composition; (2) scalable approaches for producing nanomedicines with optimized bioavailability and excretion profiles; (3) particle engineering for maintaining low levels of nonspecific cytotoxicity and sufficient stability during storage; (4) optimization of surface chemistries for maximum targeted delivery and minimum nonspecific adsorption; (5) practical methods for quantifying ligand density and distributions on multivalent nanocarriers; and (6) the design of multifunctional nanomedicines for novel combination therapies with supportable levels of bioaccumulation.

Enhancing and initiating phage-based therapies

“…An example is Doxil, a product already in use for »20 y. Doxil is based on loading the drug, doxorubicin, in liposomes. [44][45][46][47] (3) The effectiveness of Doxil is increased by the hyper-loading of doxorubicin. The hyper-loading is performed by, first, generating an inside-liposome-to-outside-liposome decreasing ammonium sulfate concentration gradient and, then, allowing diffusion-driven "running down" of this gradient in the presence of doxorubicin.…”

“…The targeting ligands include transferrin and folate. [44][45][46][47] (5) Drug release from DDVs is, in theory, achievable via conditions in the lysosomes of targeted cells. These conditions include the lowered pH of lysosomes, typically lower than 4.…”

“…Drug leaking occurs with those current DDVs loaded without covalent attachment to the DDV. [44][45][46][47] However, covalent attachment is not necessary to prevent leaking (below).…”

“…Storage stability is another, obvious factor. 45,47 The National Institute of Standards (USA) allows use of the term, monodisperse, when size uniformity is equivalent to §2% for a Gaussian distribution. 45,50 Uniformity would presumably also be an advantage for obtaining FDA approval.…”

“…47 PEG has been coated on the surface of some DDVs primarily for the purpose of evading the RES. [44][45][46][47] Nonetheless, for other particles, distribution of both R E and s can be observed by use of a high-resolution, 2-dimensional, native gel electrophoresis. 51 Investigators apparently have not yet tried this procedure for DDVs.…”