Paclitaxel-nanocrystals-loaded network thermosensitive hydrogel for localised postsurgical recurrent of breast cancer after surgical resection

Abstract

The recurrence of cancer after local surgery has been a difficult problem in the clinic for a long time. In recent years, local treatment via drug-loaded thermosensitive hydrogels have become a promising strategy to prevent cancer recurrence. Thus, a thermosensitive hydrogel based on poloxamer 407, poloxamer 188 and the bioadhesive excipient carbomer 974P was designed to locally release paclitaxel and prevent local tumour recurrence after direct smearing of the hydrogel at the site of injury in the surgical cavity. To improve the local drug concentration, paclitaxel was prepared into nanocrystals via a wet mill process. A series of studies were performed on this paclitaxel nanocrystal thermosensitive hydrogel (PTX-NCS-gel), including examination of its rheological properties and in vitro release and dissolution studies. Moreover, a postoperative tumour recurrence mouse model was established to evaluate the antitumour effects of this thermosensitive hydrogel. The results showed that PTX-NCS-gel had a clear, regular network structure with excellent temperature sensitivity and could be gelated within minutes at 33.1 °C. Additionally, the rheological property investigation indicated that the hydrogel has proper viscoelasticity and self-recovery ability. In vivo imaging showed that PTX-NCS-gel inhibited both local tumour recurrence and distant metastasis. Moreover, PTX-NCS-gel has the following advantages: it is more convenient to administer, avoids strong allergic responses, and has fewer side effects on the liver and spleen. This hydrogel has the potential to serve as a powerful auxiliary medication to prevent postoperative local tumour recurrence.

Keywords: Breast cancer; Nanocrystals; Paclitaxel; Recurrence; Thermosensitive hydrogel; Wet medium grinding technology.