title: Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment.
abstract: The solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)-coated CPT nanocomposite by means of a simple heat-treatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid cross-membrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.
authors.affiliation: Department of Biomedical Engineering, Chemistry, and Biological Sciences, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Hoboken, New Jersey, USA.
authors.forename: Honglei
authors.initials: H
authors.lastname: Zhan
authors.forename: Jun F
authors.initials: JF
authors.lastname: Liang
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001888:Boric Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002166:Camptothecin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001888:Boric Acids; C032688:boric acid; D002166:Camptothecin