In this study, a pH-responsive drug carrier was developed for the controllable release of drugs in the gastric environment. Chitosan (CS), a pH-sensitive biopolymer, and laponite RD (LAP), a nano-clay with a high drug-loading capability, were used to design the new carrier. Hydroxyapatite (HA) was grafted into CS/LAP matrix through a simple co-precipitation technique to overcome the burst release of the CS/LAP. The structural analysis and swelling tests of products demonstrated that the co-precipitation method has led to the penetration of HA nanoparticles inside the CS/LAP matrix and occupying its hollow pores. Occupation of the empty pores can lead to the entrapment of drug molecules, thereby reducing the release rate. The nanocomposite showed a high loading capacity to ofloxacin as a drug model. The effects of HA content on release behavior of nanocomposite were investigated at simulated gastric (pH 1.2) and intestine (pH 7.4) environments. The results indicated a high pH sensitivity for CS/LAP/HA. HA grafting reduced the release rate remarkably regardless of pH. The release rate of CS/LAP/HA decreased by 44–63% in pH 1.2 and 41–51% in pH 7.4 compared to CS/LAP. Kinetic studies indicated that grafting the HA in CS/LAP has changed the drug release mechanism.
