d-α-tocopheryl polyethylene glycol 1000 succinate surface scaffold polysarcosine based polymeric nanoparticles of enzalutamide for the treatment of colorectal cancer: In vitro, in vivo characterizations.

In this study, Enzalutamide (ENZ) loaded Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles coated with polysarcosine and d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared using a three-step modified nanoprecipitation method combined with self-assembly. A three-factor, three-level Box-Behnken design was implemented with Design-Expert® software to evaluate the impact of three independent variables on particle size, zeta potential, and percent entrapment efficiency through a numeric optimization approach. The results were corroborated with ANOVA analysis, regression equations, and response surface plots. Field emission scanning electron microscopy and transmission electron microscope images revealed nanosized, spherical polymeric nanoparticles (NPs) with a size distribution ranging from 178.9 ± 2.3 to 212.8 ± 0.7 nm, a zeta potential of 12.6 ± 0.8 mV, and entrapment efficiency of 71.2 ± 0.7 %. The latter increased with higher polymer concentration. Increased polymer concentration and homogenization speed also enhanced drug entrapment efficiency. In vitro drug release was 85 ± 22.5 %, following the Higuchi model (R2 = 0.98) and Fickian diffusion (n < 0.5). In vitro cytotoxicity assessments, including Mitochondrial Membrane Potential Estimation, Apoptosis analysis, cell cycle analysis, Reactive oxygen species estimation, Wound healing assay, DNA fragmentation assay, and IC50 evaluation with Sulforhodamine B assay, indicated low toxicity and high efficacy of polymeric nanoparticles compared to the drug alone. In vivo studies demonstrated biocompatibility and target specificity. The findings suggest that TPGS surface-scaffolded polysarcosine-based polymer nanoparticles of ENZ could be a promising and safe delivery system with sustained release for colorectal cancer treatment, yielding improved therapeutic outcomes.

CD44 targeted delivery of hyaluronic acid-coated polymeric nanoparticles against colorectal cancer.

Aim: To develop hyaluronic acid (HA)-coated poly-lactic-co-glycolic acid (PLGA)-polysarcosine (PSAR) coupled sorafenib tosylate (SF) polymeric nanoparticles for targeted colon cancer therapy. Materials & methods: PLGA-PSAR shells were encapsulated with SF via nanoprecipitation. Interactions were examined with transmission electron microscopy, revealing formulation component interactions. Results: The optimized HA-coated polymeric nanoparticles (238.8 nm, -6.1 mV, 68.361% entrapment) displayed enhanced controlled release of SF. These formulations showed superior cytotoxicity against HCT116 cell lines compared with free drug (p < 0.05). In vivo tests on male albino Wistar rats demonstrated improved pharmacokinetics, targeting and biocompatibility. HA-coated PLGA-PSAR-coupled SF polymeric nanoparticles hold potential for effective colorectal therapy. Conclusion: Colon cancer may be precisely targeted by HA-coated PLGA-PSA-coupled SF polymeric nanoparticles.

Fabrication of D-α-tocopheryl polyethylene glycol 1000 succinates and human serum albumin conjugated chitosan nanoparticles of bosutinib for colon targeting application; in vitro-in vivo investigation.

For more effective chemotherapy and targeted treatment of colorectal cancer, this study seeks to develop chitosan (CH)-human serum albumin (HAS)-D-α-tocopheryl polyethylene glycol 1000 (TPGS) nanoparticles (BOS-CH-HSA-TPGS-NPs) coated with Bosutinib (BOS). Nuclear magnetic resonance (NMR) indicated that chitosan's structure was modified by carbodiimide coupling with HSA. We used a Box-Behnken design to find the ideal region for particle size, zeta potential, and entrapment efficiency, eventually emerging at a formulation with these values: 187.14 ± 3.2 nm, 76.2 ± 0.96 %, and 21.1 ± 2.3 mV. Differential scanning calorimetry (DSC), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), High-performance liquid chromatography (HPLC) were all used to characterize the sample in detail. At a phosphate buffer pH of 7.4, in vitro drug release tests showed both Higuchi model release (0.954) and Fickian diffusion (n = 0.5). Compared to free BOS, HCT116 cell lines showed considerably higher cytotoxicity in in vitro cytotoxicity assays. In male albino Wistar rats, the BOS-CH-HSA-TPGS-NPs also showed enhanced pharmacokinetics, targeting efficiency, and biocompatibility. When used to the treatment of colorectal cancer, the BOS-CH-HSA-TPGS NPs show promise as a sustained-release therapy with improved therapeutic effects by addressing the challenges of poor solubility, poor permeability, and toxic side effects.

Evidence-based capacity of natural cytochrome enzyme inhibitors to increase the effectivity of antineoplastic drugs.

Cytochrome (CYP) enzymes catalyze the metabolism of numerous exogenous and endogenous substrates in cancer therapy leading to significant drug interactions due to their metabolizing effect. CYP enzymes play an important role in the metabolism of essential anticancer medications. They are shown to be overexpressed in tumor cells at numerous locations in the body. This overexpression could be a result of lifestyle factors, presence of hereditary variants of CYP (Bio individuality) and multi-drug resistance. This finding has sparked an interest in using CYP inhibitors to lower their metabolizing activity as a result facilitating anti-cancer medications to have a therapeutic impact. As a result of the cytotoxic nature of synthetic enzyme inhibitors and the increased prevalence of herbal medication, natural CYP inhibitors have been identified as an excellent way to inhibit overexpression sighting their tendency to show less cytotoxicity, lesser adverse drug reactions and enhanced bioavailability. Nonetheless, their effect of lowering the hindrance caused in chemotherapy due to CYP enzymes remains unexploited to its fullest. It has been observed that there is a substantial decrease in first pass metabolism and increase in intestinal absorption of chemotherapeutic drugs like paclitaxel when administered along with flavonoids which help suppress certain specific cytochrome enzymes which play a role in paclitaxel metabolism. This review elaborates on the role and scope of phytochemicals in primary, secondary and tertiary care and how targeted prevention of cancer could be a breakthrough in the field of chemotherapy and oncology. This opens up a whole new area of research for delivery of these natural inhibitors along with anticancer drugs with the help of liposomes, micelles, nanoparticles, the usage of liquid biopsy analysis, artificial intelligence in medicine, risk assessment tools, multi-omics and multi-parametric analysis. Further, the site of action, mechanisms, metabolites involved, experimental models, doses and observations of two natural compounds, quercetin & thymoquinone, and two plant extracts, liquorice & garlic on CYP enzymes have been summarized.