| Compared with conventional forms of dosage, controlled drug delivery systems display many advantages, including greater efficacy and safety, etc, thus receiving burgeoning attention. Presently, although the studies of controlled drug delivery systems have made great progress, the traceable drug carriers are still a challenge in the controlled drug delivery systems.Calcium titanate has good chemical stability and biocompatibility, combined with the electrospinning technology, we prepared calcium titanate nanofibers as drug carrier. For real-time monitoring of the drug release process from drug carriers, we designed the near-infrared (NIR) functionalized calcium titanate porous nanofibers for drug delivery applications. The NIR light allows for deep excitation light penetration, low autofluorescence and light scattering effect through tissue. Further, NIR range at 750～850 nm is known as the first near-infrared window (NIR Ⅰ), and 1000～1400 nm is also called as the second near-infrared window (NIR Ⅱ). Both NIR Ⅰ and NIR Ⅱ are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. The main achievements of this work are summarized as follows:(1) The synthesis of porous calcium titanate (CaTiO3, CTO) nanotubes with controlled microstructure was demonstrated via a single-nozzle electrospinning approach. Homogenous sols comprising polyvinylpyrolidine (PVP), Pluronic F127 and CTO (metal salt) were electrospun, which resulted in fine CTO nanotubes due to phase separation phenomenon. PVP/CTO molar ratio was confirmed to induce the effective manipulation of its structural characteristics. Altering the ratio from 0.24 m to 0.12 m was found to result in the increased fiber diameter, from～105 nm to～230 nm, and the enhanced hollow structure (diameter of～70nm).(2) Calcium titanate nanofibers with controlled microstructure were fabricated by a combination of sol-gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO3 nanofibers to be transformed from fibers with a circular cross section to curved ribbon-like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug-loading capacity and drug-release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127. The nanofibers synthesized without F127 present the highest drug-loading capacity and the most sustained release kinetics.(3) We propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR Ⅰ to emit NIR Ⅱ light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR Ⅱ emission intensity. We first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming Pluronic F127, followed by annealing to remove the organic components. After a model drug, Ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline solution (PBS) was investigated by detecting the NIR Ⅱ emission from the nanofibers. We found that the release of drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR Ⅱ emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR Ⅱ emission, allowing us to monitor the drug release by simply detecting the intensity of NIR Ⅱ from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+-doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics for controlled drug delivery systems. |
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