Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies

Abstract

Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignant diseases. Recently, there has been an increased focus on using nanotechnology to resolve most of the limitations in conventional chemotherapy. Niosomes have great advantages that overcome the drawbacks associated with other lipid drug delivery systems. They are simple, cheap, and highly stable nanocarriers. This study investigated the effectiveness of using niosomes with their amphiphilic characteristics in the incorporation of both hydrophilic and hydrophobic anticancer drugs for CRC treatment. Methods: Drug-free niosomes were formulated using a response surface D-optimal factorial design to study the cholesterol molar ratio, surfactant molar ratio and surfactant type effect on the particle size and Z-potential of the prepared niosomes. After numerical and statistical optimization, an optimized formulation having a particle size of 194.4 ± 15.5 nm and a Z-potential of 31.8 ± 1.9 mV was selected to be loaded with Oxaliplatin and Paclitaxel separately in different concentrations. The formulations with the highest entrapment efficiency (EE%) were evaluated for their drug release using the dialysis bag method, in vitro antitumor activity on HT-29 colon cancer cell line and apoptosis activity. Results: Niosomes prepared using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at a molar ratio 4, cholesterol (2 molar ratio) and loaded with 1 molar ratio of either Oxaliplatin or Paclitaxel provided nanosized vesicles (278.5 ± 19.7 and 251.6 ± 18.1 nm) with a Z-potential value (32.7 ± 1.01 and 31.69 ± 0.98 mV) with the highest EE% (90.57 ± 2.05 and 93.51 ± 2.97) for Oxaliplatin and Paclitaxel, respectively. These formulations demonstrated up to 48 h drug release and increased the in vitro cytotoxicity and apoptosis efficiency of both drugs up to twice as much as free drugs. Conclusion: These findings suggest that different formulation composition parameters can be adjusted to obtain nanosized niosomal vesicles with an accepted Z-potential. These niosomes could be loaded with either hydrophilic drugs such as Oxaliplatin or hydrophobic drugs such as Paclitaxel. Drug-loaded niosomes, as a unique nanomicellar system, could enhance the cellular uptake of both drugs, resulting in enhanced cytotoxic and apoptosis effects against HT-29 colon cancer cells. Oxaliplatin–niosomes and Paclitaxel–niosomes can be considered promising alternative drug delivery systems with enhanced bioavailability of these two anticancer drugs for colorectal cancer treatment.

Preparation and Characterization of Patch Loaded with Clarithromycin Nanovesicles for Transdermal Drug Delivery

“…Our findings were in line with those of Akbari et al [ 46 ], who observed that the PS of niosomes significantly dropped from 444.27 ± 4.86 to 383.67 ± 5.03 nm ( p = 0.0001) as the ratio of Chol: surfactant increased from 0:10 to 5:5. El-far et al [ 47 ] reported that a greater Chol: Tween 80 ratio significantly reduced the particle size of niosomes. This is because higher Chol levels in niosomes results in a greater bilayer hydrophobicity, which raises the surface energy and reduces the particle size [ 38 , 48 ].…”

Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment

“…The PDI as shown in Table 4 and Figure 1(B) , ranged from 0.349 to 0.629. The polydispersity index (PDI) represents the degree of any colloidal system homogeneity by indexing the size of the formed nanoparticle system distribution (El-Far et al., 2022 ). The PDI value should be less than 0.7 as the smaller PDI is the narrower particles’ size distribution and forming a homogenous, monodisperse system (Abdellatif et al., 2019 ).…”

“…The science of nanotechnology and nanosystems has been drastically enhanced over the last few decades for its multiple advantages. The unique properties of nanosized drug-delivery systems resulting from small sized particles as well as the large surface area of the vesicles could improve drugs’ solubility, bioavailability, and passive targeting properties (El-Far et al., 2022 ). Nanoparticles can penetrate cells more easily and efficiently than larger particles, resulting in better drug delivery, particularly when the drugs are generally either loaded on the particles’ surface or involved in their matrix, achieving the highest bioavailability with the fewest side effects by utilizing site-specific drug delivery (Suri et al., 2007 ).…”

Composition, preparation methods, and applications of nanoniosomes as codelivery systems: a review of emerging therapies with emphasis on cancer

“…The system remarkably decreased MCF-7 cell growth to a greater extent than the free PTX/CUR combination (Table 4). The combination of PTX with niosomes and another anticancer drug, oxaliplatin (OXP), has been studied by El-Far et al 130 to encapsulate drugs in an optimized niosome and develop their therapy results against colorectal cancer. Delivering dual drug-loaded niosomes altered the release profile compared with that of their free drugs, as they revealed a widened drug release, causing a reduction in their toxicity.…”