Paclitaxel Encapsulated in Halloysite Clay Nanotubes for Intestinal and Intracellular Delivery

• Published in: Journal of pharmaceutical sciences Vol. 106; no. 10; pp. 3131 - 3139
• Main Authors: Yendluri, Raghuvara, Lvov, Yuri, de Villiers, Melgardt M., Vinokurov, Vladimir, Naumenko, Ekaterina, Tarasova, Evgenya, Fakhrullin, Rawil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017
• Subjects: A549 Cells; Aluminum Silicates - chemistry; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; clay nanotubes; Drug Liberation - drug effects; Excipients - chemistry; halloysite; HeLa Cells; Humans; Intestines - metabolism; intracellular delivery; intracellular delivery drug release; Nanotubes - chemistry; paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Particle Size; pH-sensitive drug release; Polymers - chemistry; tablets; Tablets - administration & dosage; Tablets - chemistry; clay nanotubes; paclitaxel; halloysite; pH-sensitive drug release; intracellular delivery; tablets; intracellular delivery drug release
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2017.05.034

Naturally formed halloysite tubules have a length of 1 μm and lumens with a diameter of 12-15 nm which can be loaded with drugs. Halloysite’s biocompatibility allows for its safe delivering to cells at a concentration of up to 0.5 mg/mL. We encapsulated the anticancer drug paclitaxel in halloysite and evaluated the drug release kinetics in simulated gastric and intestinal conditions. To facilitate maximum drug release in intestinal tract, halloysite tubes were coated with the pH-responsive polymer poly(methacrylic acid-co-methyl methacrylate). Release kinetics indicated a triggered drug release pattern at higher pH, corresponding to digestive tract environment. Tablets containing halloysite, loaded with paclitaxel, as a compression excipient were formulated with drug release occurring at a sustained rate. In vitro anticancer effects of paclitaxel-loaded halloysite nanotubes were evaluated on human cancer cells. In all the treated cell samples, polyploid nuclei of different sizes and fragmented chromatin were observed, indicating a high therapeutic effect of halloysite formulated paclitaxel.