Table 3.

Modified PTX NC formulations for local and intraperitoneal drug delivery.

PTX NC	Route of Administration	Method of Preparation	The Models Used and the Reference or Control Formula	Benefits, Aims, and Other Notes	Ref.
PTX NC-loaded PECT hydrogels	Local delivery and peritumoral administration	PTX NCs were prepared by three-phase nanoparticle engineering technology (3PNET), while PTX-NC-based PECT (PTX-NC-PECT) gel was prepared based on the “cold” method	The new formula was compared to a nanoparticle-based system (PTX-NP-PECT) and controlled hydrogel of Pluronic® F127 In vitro models: release study In vivo model: MCF-7 tumor-bearing mouse models	High loading capacity of the drug. In vitro release was more effective and homogeneous. In vivo near-infrared fluorescence (NIRF) imaging indicated the ability to maintain the payloads of 1,1-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) at a peri-tumoral site for about 21 days. Exhibited the most complete release system with the greatest anti-tumor efficacy and apoptosis effect.	[181]
Silica-coated PTX NCs Si	Intra-peritoneal (IP)	Precipitation–resuspending method	The new formula was compared to uncoated PTX-NC or Abraxane Cell culture model: neural stem cells and OVCAR-8 cells In vivo model: athymic nude mice which inoculated with 2 M OVCAR-8.eGFP.ffluc human ovarian cancer cells	More effective in loading neural stem cells (NSCs). In vivo studies showed that loaded NSCs preserved their migratory ability and, for low PTX dose, were more effective against ovarian tumors.	[182]
Poly-tannic acid-coated PTX NCs (PTA-PTX NCs)	Intertumoral injection	The NCs were prepared using the thin-film hydration method followed by probe sonication	The new formula was compared with or without laser irradiation to PTX Cell culture models: 4T1, A549, and HepG2 cells In vivo model: 4T1 tumor-bearing mice	PTX NCs were prepared to act as a chemo-therapeutic agent and poly-tannic acid (pTA)-coated PTX NCs in the presence of Fe3+ acting as a potential agent for photothermal therapy (PTT). The cellular uptake was significantly improved. A synergistic effect with laser irradiation was observed. Demonstrated mild photothermal effect in vivo and the greatest effect in tumor inhibition upon laser irradiation.	[183]
PTX NC with F127 hydrogel	Intertumoral injection	Precipitation–resuspending method. The cold method was used for hydrogel preparation.	The new formula was compared to PTX or PTX microcrystal-based hydrogels In vitro erosion of the hydrogels and drug release In vivo model: 4T1 tumor-bearing BALB/c mice	PTX NCs gel offered optimum properties with high drug loading combined with moderate drug release and erosion profiles. Superior anti-tumor efficacy in 4T1 tumor-bearing BALB/c mice.	[184]
In situ cross-linkable hydrogel depot containing PTX NCs	Intraperitoneal (IP)	Anti-solvent and temperature-induced crystallization method	The new formula was compared to Taxol® and microparticulate PTX precipitates (PPT) Cell culture models: SKOV3 cells In vivo model: healthy Balb/c mice for toxicity studies and Balb/c mice (SKOV3-Luc) cell-bearing mice for the efficacy study	Superior killing efficiency and more toxicity in SKOV3 cell line. The in vivo study indicated improved dissolution, cellular uptake, and lower maximum tolerated dose. It also showed that a single IP dose was sufficient in extending the survival of tumor-bearing mice.	[185]
PTX-NCs combined with niclosamide (NLM) NLM-NCs co-loaded PLGA-PEG-PLGA thermosensitive hydrogel (PN-NCs-Ts)	Intratumoral injection	PTX-NCs were prepared by the “3PNET” method	The new formula was compared to PTX-NCs, PTX-NCs-Ts Gel, NLM-NCs, NLM-NCs-Ts gel, and PN–NCs-Ts gel In vitro drug release Cell culture models: MDA-MB-231 cells In vivo model: BALB/c nude mice inoculated with MDA-MB-231 cells	Sustained and significantly delayed drug release both in vitro and in vivo. The combination with NLM improved PTX cellular uptake, apoptosis, and provided inhibition of cell migration. The in vivo studies showed significant inhibition of tumor growth with acceptable safety and effectively overcoming it. Triple-negative breast cancer (TNBC) progress and drastically prevented breast cancer stem cells (BCSCs).	[186]