ABSTRACT
á´ -cycloserine (DCS), an FDA-approved medicine for the treatment of tuberculosis, is also a partial agonist at the glycine recognition site of N-methyl-á´ -aspartate (NMDA) receptor and has shown significant treatment efficacy for central nervous system (CNS) disorders including depression, schizophrenia, Alzheimer's disease, and post-traumatic stress disorder. The physicochemical properties of DCS, however, limit the options of formulation and medicinal applications of DCS, and warrants further investigation for the development of CNS therapeutics. Nanocrystals play an important role in pharmaceutic design and development. The properties of nanocrystals are remarkably different from their bulk material counterpart, attributed to the large surface-area-to-volume ratio which can improve the bioavailability. In this study, for the first time, DCS, a highly water-soluble compound, has formed nanocrystals and this was confirmed by scanning electronic microscopy and X-ray powder diffraction. Furthermore, DCS nanocrystals were applied to several formulations to test their stability and then to the in vitro Franz diffusion test with reservoir patch formulation as well as in vivo pharmacokinetics study with enteric capsules. We tested these formulations regarding their nanocrystal physical properties, size effect, and dissolution rate, respectively. We found that DCS nanocrystals showed good performance in the Franz diffusion test and rodent pharmacokinetic studies due to the nanoparticle size and faster dissolution as compared with the commercial DCS powder. These DCS nanocrystal formulations could offer a new approach for the development of an advanced drug delivery system for the treatment of CNS disorders.
ABSTRACT
OBJECTIVES: The aim of this study was to develop a new material with integrated interface design that could achieve the purpose of environmental-sensing controlled release against cariogenic bacteria. Furthermore, this material can rebalance oral flora and serve as a preventive and reparative measure of dental caries. MATERIALS AND METHODS: NaF@PAA@HA@polyelectrolytes@HA@PAA particles were synthesized using the method of two-solution phases precipitation followed by biocompatible polymers coating layer by layer. The structure of the particles was confirmed by transmission electron microscope. The fluoride release profile was measured by fluoride ion electrode. Antimicrobial activity against the cariogenic microorganisms was analyzed by scanning electron microscopy and energy dispersive spectrum. The efficacy experiments were conducted on tooth enamel slides to evaluated fluoride absorption and antibacterial activity of the prototype toothpaste containing microcube particles RESULTS: The structure of NaF@PAA@HA@polyelectrolytes@HA@PAA particles showed a core surrounded by tooth-adhesion polymer layers in thin fin or filament structure. The loaded concentration of fluoride in the particles' core was 148,996 ± 28,484 ppm. NaF@PAA@HA@polyelectrolytes@HA@PAA particles showed selective inhibition of cariogenic microorganisms over probiotic strains and stronger fluoride adhesion on tooth enamel. A burst release (over 80%) of fluoride from the particle-containing toothpaste was observed under cariogenic acidic environment (pH < 5), while it remained extremely low under neutral environment. Compared with the best results of commercial toothpastes, our prototype toothpaste increased enamel fluoride uptake by 8-fold in normal enamel slides and by 11-fold in the slides with induced white spot lesions after either 1- or 7-day treatment. The prototype toothpaste also showed better inhibition of cariogenic microorganisms than the commercial brands. The coverage area of cariogenic bacteria under our toothpaste treatment was 73% on normal enamel slides compared with the commercial brands, while it was 69% in the induced white spot lesions. CONCLUSIONS: In our study, an intelligent toothpaste was developed that selectively inhibits cariogenic bacteria by microenvironment proton-triggered fluoride release. Such novel design would accomplish a favorable flora balance for optimal long-term oral health.
