There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through Git.Oral dosage forms of medications are generally a convenient dosage form for drug delivery 1,2 . However, one of the main challenges in drug delivery is to overcome gastric barriers and preventing the drug release in the stomach 3 . There was a huge increase in the development of orally delivered anti-cancer agents in the past 10 years, as a quarter of all available anti-cancer drugs are now administered orally 4 . Colorectal cancer is one of the most common forms of malignancy and the fourth most common contributor to cancer mortalities 5 . Moreover, targeting specific cells in cancer therapy provides an advantageous way to treat cancer directly 6-10 . For example, the release of drug in the colon and drug particles can be driven by octreotide (OCT) and bind to somatostatin receptors (SSTRs), which are a component of ligand-mediated targeting 8 . The inhibition effect of somatostatin (SST) analogues on tumor cells is one effective approach to cancer therapy. Moreover, SST and its analogues have open Scientific RepoRtS | (2020) 10:4736 | https://doi.org/10.1038/s41598-020-61605-y www.nature.com/scientificreports www.nature.com/scientificreports/ shown proliferative inhibition of colon cancer cell lines 11 . There are five subtypes of SSTRs expressed in colorectal cancer, and SSTR1 is the most prevalent compared to the others 12 .Cetuximab (CTX) is a recombinant monoclonal antibody drug used in the...

There is a need to synthesize eco-friendly nanoparticles with more effective and potent antibacterial activities. A green and cost-effective method for the synthesis of silver nanoparticles (AgNPs) using Thymus vulgaris, Mentha piperita, and Zingiber officinale extracts was developed. The analytical instrumentation, namely, UV/Vis, absorption spectroscopy, FTIR, and scanning electron microscopy (SEM), was used to determine the developed AgNPs, confirming the functional groups involved in their reduction. Acidic molybdate, DPPH, and FRAP regents were reacted with AgNPs extract to evaluate their antioxidant, scavenging, and oxidative activities. The agar well diffusion method was used to determine the antibacterial potential of AgNPs extracts using clinical isolates. The developed AgNPs showed peaks at 25 cum\Diff, 50 cum\Diff, and 75 cum\Diff, respectively, of 16.59 ± 0.78, 45.94 ± 1.07, and 81.04 ± 0.98 nm, for Thymus vulgaris, Mentha piperita, and Zingiber officinale. SEM revealed uniform prepared and encapsulated AgNPs by plant extracts matrix. The FTIR shows the involvement of amide (-CO-NH2), carbonyl (-CO), and hydroxyl (-OH), which resulted in the reduction of AgNPs. The AgNPs extract showed significantly higher TAA, DPPH, and FRAP values than free AgNPs and plant extract ( p < 0.05 ). Antibacterial of AgNPs extracts revealed various degrees of inhibition zones against Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. The developed AgNPs extract showed acceptable antioxidant activities and noticeable antibacterial potential. The prepared green synthesized AgNPs showed a promising antibacterial activity against four multidrug-resistant clinical isolates, Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. Further, fractionated extracts other than crude extracts will be utilized in the preparation of AgNPs to get more efficient antibacterial activities for future work.

Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

Differential scanning calorimetry has been employed to study the thermal effects of vinblastine sulfate upon aqueous, single and multiple bilayer dispersions of 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC). The calorimetric results summarized to an increase in the gel to liquid-crystalline phase transition enthalpy and the abolishment of the L h V(gel phase) to P h V(ripple phase) pretransition for the uni-and multilamellar dispersions, as well as an increase in the transition temperature T m and the transition cooperativity for single bilayer DPPC/ vinblastine mixed vesicles, are consistent with an induced, partially interdigitated, gel phase. Computational analysis has been successfully applied to clarify the intermolecular effects and verify the feasibility of the proposed interdigitation for the vinblastine sulfate molecules and also for the ursodeoxycholic acid (UDCAH) and bromocylated taxanes, which have been shown to induce an interdigitated gel phase in DPPC bilayers.

Thymoquinone (TQ), which is one of the main bioactive constituents of Nigella sativa seeds, has demonstrated its potential against various cancer models. The poor solubility of TQ in aqueous solution limits its uses in clinical application. The present study aimed to develop a novel formulation of TQ to increase its bioavailability and therapeutic potential with minimal toxicity. Polyethylene glycol (PEG)-coated DSPC/cholesterol comprising TQ liposomes (PEG-Lip-TQ) were prepared and characterized on various aspects. A computational investigation using molecular docking was used to assess the possible binding interactions of TQ with 12 prospective anticancer drug targets. The in vitro anticancer activity was assessed in A549 and H460 lung cancer cells in a time- and dose-dependent manner, while the oral acute toxicity assay was evaluated in silico as well as in vivo in mice. TQ docked to the Hsp90 target had the lowest binding energy of −6.05 kcal/mol, whereas caspase 3 was recognized as the least likely target for TQ with a binding energy of −1.19 kcal/mol. The results showed 96% EE with 120 nm size, and −10.85 mv, ζ-potential of PEG-Lip-TQ, respectively. The cell cytotoxicity data demonstrated high sensitivity of PEG-Lip-TQ and a several fold decrease in the IC50 while comparing free TQ. The cell cycle analysis showed changes in the distribution of cells with doses. The in vivo data revealed an ~9-fold increase in the LD50 of PEG-Lip-TQ on free TQ as an estimated 775 and 89.5 mg/kg b.w, respectively. This study indicates that the pharmacological and efficacy profile of PEG-lip-TQ is superior to free TQ, which will pave the way for an exploration of the effect of TQ formulation in the treatment of lung cancer in clinical settings.