Abstract
Drug nanocrystals (NCs) can improve the solubility and bioavailability of insoluble drugs for oral administration. However, the biocompatibility and mechanisms of transmittance of drug NCs through the intestinal epithelial tissue are still not well understood. In this work, the physico-chemical properties and interactions with biomolecules in oral delivery pathways, as well as the transmittance through mimical intestinal epithelial cells, of NCs of paclitaxel (PTX) are investigated. PTX was previously demonstrated to be an effective anti-cancer drug. It is found that maximum 1% (w/v) poly(styrenesulfonate) is sufficient to keep PTX NCs monodisperse in varied biological environments and presents no significant interaction with extracellular biomolecules for at least 24 h. The concentration of PTX NCs is kept carefully controlled to avoid serious toxicity to cells (10 µg ml−1 in our experiments but this also depends on NC size). The transmittance of PTX NCs through mimical intestinal epithelial reached 25% in 6 h, demonstrating its comparatively high oral bioavailability in the human body. This work demonstrates the great potential of PTX NC treated in oral delivery.
Highlights
Oral administration of drugs is generally the preferred route compared to the parenteral route due to its convenience, safety2017 The Authors
A droplet of the solution was deposited on a clean flat silicon surface and let sit for 5 min, the surface was dried with a gentle nitrogen flow before being imaged with either a Bruker atomic force microscope (AFM) or Hitachi scanning electron microscope (SEM)
No significant interactions between PSS-modified PTX NCs and pepsin/trypsin were observed in gastrointestinal tract environments, suggesting PTX NCs’ ability to pass through gastrointestinal tracts with little interference to intestinal epithelial cells
Summary
Oral administration of drugs is generally the preferred route compared to the parenteral route due to its convenience, safety2017 The Authors. The goal of formulating NCs is to prolong the metabolism of drugs in the body, enhance their bioavailability, decrease the surface–volume ratio of drug and solve the problem of poor solubility [9,10,11,12]. PTX NCs have been demonstrated to exhibit efficient anti-cancer activity [19,20] and are a highly desired candidate for oral administration. The investigation of the interactions between PTX NCs and biomolecules, especially enzymes, and their transmittance across the intestinal epithelium is of great interest for clinical applications [21,22,23]
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