Remote Loading of Hydrophilic Drug into Cubosomes by Transmembrane pH-Gradient and Characterization of Drug-Loaded Cubosomes Prepared by Different Method.

The encapsulation efficiency (EE) of hydrophobic drug into cubosomes was high by conventional methods, while poor for the hydrophilic drug. In this study, a remote loading method based on transmembrane pH-gradient was applied to prepare hydrophilic drug loaded cubosomes. Several hydrophilic drugs were selected and studied. Results showed just part of the investigated drugs were successfully loaded into cubosomes by the remote loading method, whereas all the drugs failed to be encapsulated by the high-pressure homogenization method. The EE based on remote loading method was affected by the solubility, LogP, number of rings, and polarizability of the drug independent of the number of hydrogen acceptor and hydrogen donor. And the drugs that had high EE by remote loading method were BCS class 1 or 2. In addition, the EE base on remote loading method was significantly affected by the external water pH of cubosomes and drug concentration. The size of drug-loaded cubosomes by remote loading method mainly depended on the pre-formed blank cubosomes, which was bigger than that by high-pressure homogenization method. The preparation method affected the liquid crystalline structure of acidic drug loaded cubosomes, while showed no obvious effect on that of basic drug loaded cubosomes. The release of drug was susceptible to the pH of release medium independent of the preparation method. The drug-loaded cubosomes prepared by different method all showed favorable stability during storage. The remote loading method was a promising approach for the efficient encapsulation of hydrophilic drug into cubosomes. This study laid a foundation for the application of remote loading method on the preparation of hydrophilic drug loaded cubosomes. [Display omitted] • A remote loading method based on transmembrane pH-gradient was applied to prepare hydrophilic drug-loaded cubosomes. • The encapsulation efficiency of hydrophilic drugs in cubosomes was significantly improved using the remote loading method compared with the conventional method. • This study clarified the fact that the EE based on remote loading method was significantly affected by the solubility, LogP, number of rings, polarizability, and and BCS information of the drug independent of the number of hydrogen acceptor and hydrogen donor. • The remote loading method based on transmembrane pH-gradient was simple, rapid, and efficient, which was a promising approach for the efficient encapsulation of hydrophilic drugs into cubosomes. This study laid a foundation for the application of remote loading method on the preparation of hydrophilic drug loaded cubosomes. [ABSTRACT FROM AUTHOR]