Effective pH-responsive nanocarrier based on the anisotropic surfaces of halloysite nanotubes for controlled drug release

Abstract

Natural halloysite nanotubes (Hal) have been proved to be a promising nanocarrier in drug delivery system due to its unique tubular structure and excellent biocompatibility, but the anisotropic surfaces have not been fully exploited. Herein, a drug nanocarrier with effective pH-responsive properties based on the anisotropic surfaces of Hal is designed and investigated. The anisotropic surfaces of Hal present diverse charges under different pH, which determines whether electrostatic attraction or repulsion is generated between it and drug molecules. Ciprofloxacin, diclofenac sodium, and nicotinic acid can spontaneously attach on Hal at optimum loading pH. Ciprofloxacin is attracted by the outer surfaces and repelled by inner surfaces, while diclofenac sodium and nicotinic acid mainly loads on the inner surfaces. The drug loading of Hal can reach 33.98, 20.52 and 26.61 mg/g with the assistance of vacuum force, respectively. Chitosan and pectin are self-assembled on Hal in a layer-by-layer pattern through electrostatic attraction to obtain dually encapsulated drug nanocarriers with pH-response. The nanocarriers enables gut-specific release and prevents drug degradation in the acidic medium. Especially, pectin/chitosan/Hal-diclofenac sodium exhibits a negligible release of diclofenac sodium in simulated gastric juice and maintains a slowly release for >6 h in simulated intestinal juice, possessing a pH switch.