Development of stabilized Paclitaxel nanocrystals: In-vitro and in-vivo efficacy studies.

Objective: The aim of the study was to develop stable Paclitaxel nanocrystals (PTX/NCs) for enhanced oral delivery of Paclitaxel (PTX) by circumventing its difficult solubilization properties and rapid metabolism.

Methods: Preparation of nanocrystals (NCs) was carried out using high pressure homogenizer (Microfluidizer™) without using any organic solvent. Effect of various process and formulation parameters on development and stability of nanocrystals (NCs) were investigated. Particle characteristics, stability studies, in-vitro cellular studies and oral pharmacokinetics in male Wistar rats were examined.

Results: It was found that different stabilizer used had different effect on size reduction and stability. Surfactants (Tween 80) and low molecular weight synthetic polymer sodium poly styrene sulfonate (PSS) found more suitable and efficient compared to high molecular weight polymers glycol chitosan (GC) and sodium alginate (SA). In-vitro cytotoxicity and cell cycle arrest studies on MCF7 and MDA-MB breast cancer cell lines revealed that PTX/NCs retained the activity even after processing at high pressure and also NCs were more potent and efficacious than PTX solution. The oral in-vivo pharmacokinetic studies demonstrated that PTX/NCs exhibit significant increase in AUC0-t, Cmax, MRT and decrease in Tmax, compared to plain PTX crystals. The increase in AUC was almost 9-10 fold compared to plain PTX crystals.

Conclusion: Altogether study showed that PTX/NC can be a clinically relevant drug delivery system for oral chemotherapy as it can remarkably increases the pharmacological effect by increasing oral bioavailability.