Nanocrystals Production, Characterization, and Application for Cancer Therapy

Abstract

The delivery of synthesized drugs exhibiting poor solubility in water is extremely difficult, limiting bioavailability and causing adverse effects when solubilized. A need was determined for developing a formulation to deliver poorly water‐soluble drugs without indiscriminately reaching healthy organs and tissues. Therefore, nanocrystal formulations have been a significant focus for delivering poorly water‐soluble drugs via oral, paraenteral, and alternative routes. Using nanocrystal formulations avoids potential side effects and instability related to many existing delivery systems. Currently, few cancer therapy products are approved by the Food and Drug Administration (FDA) in which poorly soluble drugs are formulated by nanoparticles. In this chapter, the production of nanocrystals of pharmaceutical organic compounds is reviewed. Thereafter, the chapter will focus on the application of nanocrystals for cancer therapy.

Developing Nanocrystals for Cancer Treatment

“…The essence of a bottom-up process is precipitation of dissolved drug molecules, which consists of two crucial steps, nucleation and subsequent crystal growth to generate small and uniform nanocrystals. Therefore, the nucleation step needs to be carefully controlled [6]. The more nuclei formed in the nucleation stage, the less growth of each nucleus in the end.…”

“…When CO 2 is used as a solvent at its critical state to dissolve or precipitate drug crystals, the crystallization process takes advantage of easy removal of the solvent. Compared with the top-down approach, the crystallization techniques have greater potentials to produce nanocrystals with superior crystallinity and of narrow particle size distribution and uniform morphology, in addition to modest energy requirement and fewer issues of contamination from the manufacturing equipment [6,22,25]. Nanocrystals generated by the bottom-up technique are, thus, more suitable for intravenous injection of anticancer compounds.…”

“…This is due to distinctive characteristics of nanocrystals compared with other nanoparticle platforms [6,7,12]. Sans carrier chemicals, a nanocrystal formulation can not only eliminate any toxic side-effects inflicted by the encapsulating/solubilizing excipients, but also offer a drug loading as high as 100%, resulting in satisfactory therapeutic concentrations at low dose [16].…”

“…A poorly soluble drug may be encapsulated and/or solubilized by polymers, lipids or surfactants into nanosized particles suitable for intravenous administration [6]. Several nanoparticle-based delivery platforms, including liposomes, polymeric nanoparticles, solid lipid nanoparticles and micelles, have been developed for various anticancer agents [10].…”

“…This is largely due to the fact that many cancer drugs are not readily absorbed following oral administration, due to poor solubility and/or digestive tract toxicity, limiting the oral absorption below therapeutic levels. This situation will not improve because more than 40% of newly synthesized drug molecules in development are poorly water soluble [3][4][5][6]. The proportion of water-insoluble drugs developed in oncology, anti-infective and antiviral treatment is even higher [7].…”