Synthesis And Characterization Of Hydroxycamptothecin-Sebacate-LDH Nanohybrids

Hydroxycamptothecin (HCPT) as a hydrophobic anticancer drug brings many challenges in the clinical applications due to its toxic side, poor water solubility and facile structure transformation (the lactone form with bioactivity to the carboxylate form without bioactivity). To research controlled release formulation for improving its solubility and structure stability have important value for further study. Layered doubly hydroxydies (LDHs) had got increasing focus on the delivery of drug. So to prepare LDH nanohybrids with HCPT intercalated (short for HCPT-LDH) and explore the application in controlled release formulation is valuable. There have been many reports about preparation of drug-LDH nahohybrids, but water insoluble nonionic drug is not as easy to be intercalated into the gallery of LDH as water soluable anionic drug. There were some reports about preparing HCPT-LDH, but the drug loading is so low as about5%. So it is also an important subject to prepare HCPT intercalated LDH nanohybrids with high drug loading. In this particle, the nanohybrids of HCPT-LDH were prepared, and properties of controlled release, solubility of HCPT and structure stability were studied for providing a basis in exploring controlled release formulation.The main content and conclusions of this paper are as follows:(1) SC-Zn2Al-LDH and SC-Mg2Al-LDH were prepared via a secondery interaction method. First, the nanohybrid of sebacate (SC) intercalated SC-Zn2Al-LDH and SC-Mg2Al-LDH were prepared by a co-precipitation method; second, HCPT was intercalated into the LDH’s gallery in ethanol medium. Samples were characterized by XRD, SEM, FT-IR and element analysis. Results showed that HCPT were intercalated into gallery of LDH, and with an obvious higher drug loading of9.41%than early report.(2) According results of XRD, SC exists with different conditions in gallery of SC-Zn2Al-LDH and SC-Mg2Al-LDH. For SC-Mg2Al-LDH, a probably morphology of the SC molecules in the gallery of LDH was suggested that the SC molecules arranged as a bilayer structure in which two carboxylate groups of SC molecule combined onto one LDH layer surface; while for SC-Zn2Al-LDH, maybe with the long axis perpendicular to the brucite-like layer, the SC molecule interacted with two LDH layer surface. For both cases, it is acceptable that the sebacate-pillared LDH can provide a hydrophobic space to accommodate HCPT molecules. Drived by hydrophobic force, the poorly water-soluble HCPT molecules were intercalated into the hydrophobic phase formed by the alkyl chains of sebacate molecules.(3) HCPT could keep lactone form with bioactivity, and compared with pure HCPT, its solubility were obviously improved in HCPT-SC-LDH nanohybrids. It is very important for clinic application.(4) At simulated body fluid condition,37℃, pH4.8and7.2respectively, drug release behavior were explored. Results showed obvious controlled release effect and can be applied as potential drug delivery system. The release in vitro of HCPT could be fitted with the pseudo-second-order model. The release rate of HCPT from the nanohybrid at pH7.2is remarkably lower than that at pH4.8, this is due to a possible difference in the release mechanism. For the pH7.2release, the mechanism is primarily through diffusion of drug molecules; while for the pH4.8release, that is through both the dissolution of LDH layers and diffusion of drug molecules.