Table 2.

Modified PTX NC formulations for oral drug delivery.

PTX NC	Method of Preparation	The Models Used and the Reference or Control Formula	Benefits, Aims, and Other Notes	Ref.
Pluronic-grafted chitosan as a stabilizer for PTX NC (Pl-g-CH PTX NCs)	A novel Pluronic-grafted chitosan copolymer was established and then utilized as a functional stabilizer for PTX NCs. Generally, the NCs were prepared using a high-pressure homogenizer.	The new formula was compared to Taxol® Cell culture models: Caco-2 cells and B16 F10 murine melanoma cells In vivo model for oral PK evaluation: Wistar ratsIn vivo model for efficacy study: healthy Balb/C mice injected with B16 F10 murine melanoma model	Improving intra-cellular accumulation. Improving the absorption by the transcellular and paracellular routes. Showed a P-gp inhibitory property. The in vivo model demonstrated more anti-tumor efficacy and growth reduction after oral delivery, and this was related to the enhancement in the systemic circulation as both the absorption and bioavailability were improved significantly.	[177]
PTX NCs stabilized by tween 80 or low molecular weight synthetic polymer sodium polystyrene sulfonate (PSS)	The top-down method was performed using a microfluidizer as a high-pressure homogenizer that was used to prepare the NCs without using any organic solvent	The new formula was compared to formulas stabilized with high molecular weight polymers glycol chitosan (GC) and sodium alginate (SA), as well as with PTX solution and PTX-NCs Cell culture models: MCF7 and MDA-MB breast cancer cell lines In vivo model: PK in male Wistar rat model	The prepared NCs were more suitable, efficient, and exhibited a considerable increase in the dissolution rate, which indicated an enhancement in its bioavailability. The in vitro cell culture study showed more efficiency and potency in killing and inhibiting the growth of the cancer cells. In vivo pharmacokinetic studies demonstrated a considerable increase in AUC0–t, Cmax, and MRT and a decrease in Tmax.	[178]
Transferrin (TF)-modified PTX NCs	PTX NCs were prepared using the precipitation–resuspension method	The new formula was compared to Taxol® and unmodified PTX NCs In vitro models: in situ intestinal perfusion study Cell culture models: Caco-2 cells and MCF-7 cancer cells In vivo model: PK Sprague Dawley rat model	Showed an enhancement of cellular monolayer penetration. Had superior suppression in MCF-7 cell growth. Showed an enhancement of intestinal absorption. The pharmacokinetic studies also demonstrated greater Cmax and AUC than both PTX NCs and Taxol® while having the lowest tmax.	[179]
Poly(sodium pstyrenesulfonate) (PSS)-modified PTX NCs	Not mentioned	In vitro models: interactions with biomolecules in oral delivery pathways Cell culture models: Caco-2 cell lines	Suitable mono-dispersion and stability in the gastrointestinal tract (GIT) environments for at least 24 h. No substantial interactions with pepsin or trypsin enzymes were detected in the GIT environments. PSS-modified PTX NCs passed through the mimical intestinal epithelial cell (Caco-2 cell lines) with about 25% transmittance. However, the concentration of the NCs should be controlled to avoid toxic effects on the cells.	[180]