Nano- and Crystal Engineering Approaches in the Development of Therapeutic Agents for Neoplastic Diseases

Cancer is a leading cause of death worldwide. It is a global quandary that requires the administration of many different active pharmaceutical ingredients (APIs) with different characteristics. As is the case with many APIs, cancer treatments exhibit poor aqueous solubility which can lead to low drug absorption, increased doses, and subsequently poor bioavailability and the occurrence of more adverse events. Several strategies have been envisaged to overcome this drawback, specifically for the treatment of neoplastic diseases. These include crystal engineering, in which new crystal structures are formed to improve drug physicochemical properties, and/or nanoengineering in which the reduction in particle size of the pristine crystal results in much improved physicochemical properties. Co-crystals, which are supramolecular complexes that comprise of an API and a co-crystal former (CCF) held together by non-covalent interactions in crystal lattice, have been developed to improve the performance of some anti-cancer drugs. Similarly, nanosizing through the formation of nanocrystals and, in some cases, the use of both crystal and nanoengineering to obtain nano co-crystals (NCC) have been used to increase the solubility as well as overall performance of many anticancer drugs. The formulation process of both micron and sub-micron crystalline formulations for the treatment of cancers makes use of relatively simple techniques and minimal amounts of excipients aside from stabilizers and co-formers. The flexibility of these crystalline formulations with regards to routes of administration and ability to target neoplastic tissue makes them ideal strategies for effectiveness of cancer treatments. In this review, we describe the use of crystalline formulations for the treatment of various neoplastic diseases. In addition, this review attempts to highlight the gaps in the current translation of these potential treatments into authorized medicines for use in clinical practice.