No abstract

Cancer is one of the leading causes of death worldwide. Regardless of advances in understanding the molecular mechanics of cancer, its treatment is still lacking and the death rates for many forms of the disease remain the same as six decades ago. Although a variety of therapeutic agents and strategies have been reported, these therapies often failed to provide efficient therapy to patients as a consequence of the inability to deliver right and adequate chemotherapeutic agents to the right place. However, the situation has started to revolutionize substantially with the advent of novel ‘targeted’ nanocarrier-based cancer therapies. Such therapies hold great potential in cancer management as they are biocompatible, tailored to specific needs, tolerated and deliver enough drugs at the targeted site. Their use also enhances the delivery of chemotherapeutics by improving biodistribution, lowering toxicity, inhibiting degradation and increasing cellular uptake. However, in some instances, nonselective targeting is not enough and the inclusion of a ligand moiety is required to achieve tumor targeting and enhanced drug accumulation at the tumor site. This contemporary review outlines the targeting potential of nanocarriers, highlighting the essentiality of nanoparticles, tumor-associated molecular signaling pathways, and various biological and pathophysiological barriers.

Sorafenib tosylate (SFB) is a multikinase inhibitor that inhibits tumour growth and proliferation for the management of breast cancer but is also associated with issues like toxicity and drug resistance. Also, being a biopharmaceutical class II (BCS II) drug, its oral bioavailability is the other challenge. Henceforth, this report intended to encapsulate SFB into a biocompatible carrier with biodegradable components, i.e., phospholipid. The microemulsion of the SFB was prepared and characterized for the surface charge, morphology, micromeritics and drug release studies. The cell viability assay was performed on 4T1 cell lines and inferred that the IC50 value of sorafenib-loaded microemulsion (SFB-loaded ME) was enhanced compared to the naïve SFB at the concentrations of about 0.75 µM. More drug was available for the pharmacological response, as the protein binding was notably decreased, and the drug from the developed carriers was released in a controlled manner. Furthermore, the pharmacokinetic studies established that the developed nanocarrier was suitable for the oral administration of a drug by substantially enhancing the bioavailability of the drug to that of the free SFB. The results bring forth the preliminary evidence for the future scope of SFB as a successful therapeutic entity in its nano-form for effective and safer cancer chemotherapy via the oral route.

For many years, Aegle marmelos (A. marmelos) has been used medicinally and as a dietary supplement. Despite this, there are minimal research data on A. marmelos phytochemical properties and pharmacological effects. This study aimed to explore the phytoconstituents, cytotoxicity, glucose uptake, and antioxidant and antidiabetic potential of an alcoholic extract of A. marmelos leaf. The cytotoxicity of A. marmelos in HepG2 cells was tested in vitro, and the results revealed that it has strong cytocompatibility and cytoprotective properties. The extract’s antioxidant activities were investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. Antioxidant potential was shown to be quite impressive. The enzymes α-amylase and α-glycosidase were found to be substantially inhibited by A. marmelos, with IC50 values of 46.21 and 42.07 mg/mL, respectively. In HepG2 cells, A. marmelos significantly reduced ROS levels that were elevated due to high glucose and enhanced glucose consumption (p < 0.05). These activities might be due to the enrichment of bioactive phytoconstituents analyzed chromatographically using GC/MS and HPLC. The findings of this study show that A. marmelos could be an effective restorative therapy for diabetes and related diseases.