Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy

• Published in: Journal of controlled release 2017-08, Vol.259, p.203-211
• Main Authors: Kim, Jinhwan, Lee, Junseok, Lee, Yeong Mi, Pramanick, Swapan, Im, Sooseok, Kim, Won Jong
• Format: Article
• Language: English
• Subjects: Andrographolide; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Boronic Acids - administration & dosage; Boronic Acids - chemistry; Boronic Acids - therapeutic use; Boronic ester chemistry; Cell Line, Tumor; Cell Survival - drug effects; Diterpenes - administration & dosage; Diterpenes - chemistry; Diterpenes - therapeutic use; Drug delivery; Drug Delivery Systems; Drug Liberation; Female; Humans; Mice, Inbred BALB C; Mice, Nude; Nanostructures - administration & dosage; Nanostructures - chemistry; Nanostructures - therapeutic use; Neoplasms - drug therapy; Neoplasms - pathology; Phenylboronic acid; Polymerization; Polymers - administration & dosage; Polymers - chemistry; Polymers - therapeutic use; Tumor targeting
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2016.10.029

Along with the successful discovery of paclitaxel as an anticancer drug, natural products have drawn great attention in drug discovery. Recently, andrographolide (AND) from Andrographis paniculata was reported to provide several benefits, including an anticancer effect. However, the extremely low solubility of the compound in an aqueous medium was an obstacle to overcome for the systemic administration and clinical application of AND. Based on our previous report, we formulated a water-soluble nanoconstruct by forming a boronic ester between the cis-1,3-diol of AND with hydrophilically polymerized phenylboronic acid (pPBA). The release of loaded AND was controlled by intracellular conditions, specifically, by low pH and high ATP concentrations, due to the pH- and diol-dependent affinity of the boronic ester. Because of the intrinsic property of the PBA moiety, the pPBA-AND nanoconstruct exhibited an excellent tumor targeting ability both in vitro and in vivo. Finally, a significant inhibition of tumor growth was observed in vivo. Taken together, our strategy, which is based on the formulation of a soluble nanoconstruct using hydrophilically polymerized PBA and a cis-diol, is plausible and provides a delivery system for a wide variety of chemotherapeutics. This strategy has applications not only in cancer therapy but also broader fields such as anti-inflammation or immunotherapy. [Display omitted]