Aim: Multireservoir nanocarriers were fabricated for delivering antineoplastic drug cocktail from herbal and fungal origin. Monascus yellow pigments (MYPs), monascin and ankaflavin, were isolated from red-mold rice, and incorporated within casein micelles (CAS MCs) along with the herbal drug, resveratrol (RSV). Both drugs (MYPs and RSV) were simultaneously incorporated into the hydrophobic core of CAS MCs. Alternatively, MYPs-loaded CAS MCs were enveloped within RSV-phytosomal bilayer elaborating multireservoir nanocarriers. Results: Cytotoxicity studies confirmed the superiority of multireservoir nanocarriers against MCF-7 breast cancer cells. The in vivo antitumor efficacy was revealed by reduction of the tumor volume and growth biomarkers. Conclusion: Multireservoir CAS nanocarriers for codelivery of both MYPs and RSV may be promising alternative to traditional breast cancer therapy.

Inappropriate use of antibiotics in clinical settings is thought to have led to the global emergence and spread of multidrug-resistant pathogens. The goal of this study was to investigate the prevalence of genes encoding aminoglycoside resistance and plasmid-mediated quinolone resistance among clinical isolates of Klebsiella pneumoniae. All K. pneumoniae isolates were phenotypically identified using API 20E and then confirmed genotypically through amplification of the specific K. pneumoniae phoE gene. All isolates were genotyped by the enterobacterial repetitive intergenic consensus polymerase chain reaction technique (ERIC-PCR). Antibiotic susceptibility testing was done by a modified Kirby-Bauer method and broth microdilution. All resistant or intermediate-resistant isolates to either gentamicin or amikacin were screened for 7 different genes encoding aminoglycoside-modifying enzymes (AMEs). In addition, all resistant or intermediate-resistant isolates to either ciprofloxacin or levofloxacin were screened for 5 genes encoding the quinolone resistance protein (Qnr), 1 gene encoding quinolone-modifying enzyme, and 3 genes encoding quinolone efflux pumps. Biotyping using API 20E revealed 13 different biotypes. Genotyping demonstrated that all isolates were related to 2 main phylogenetic groups. Susceptibility testing revealed that carbapenems and tigecycline were the most effective agents. Investigation of genes encoding AMEs revealed that acc(6′)-Ib was the most prevalent, followed by acc(3′)-II, aph(3′)-IV, and ant(3′′)-I. Examination of genes encoding Qnr proteins demonstrated that qnrB was the most prevalent, followed by qnrS, qnrD, and qnrC. It was found that 61%, 26%, and 12% of quinolone-resistant K. pneumoniae isolates harbored acc(6′)-Ib-cr, oqxAB, and qebA, respectively. The current study demonstrated a high prevalence of aminoglycoside and quinolone resistance genes among clinical isolates of K. pneumoniae.

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.

Aim: Monascin and ankaflavin, the major fractions of the fungal-derived monascus yellow pigments, were incorporated with the herbal drug, resveratrol (RSV) within the core of folate-conjugated casein micelles (FA–CAS MCs, F1) for active targeting. PEGylated RSV-phospholipid complex bilayer enveloping casein-loaded micelles (PEGPC–CAS MCs) were also developed as passive-targeted nanosystem. Results: FA– and PEGPC–CAS MCs demonstrated a proper size with monomodal distribution, sustained drug release profiles and good hemocompatibility. The coloaded MCs showed superior cytotoxicity to MCF-7 breast cancer cells compared with free drugs. Both nanosystems exerted excellent in vivo antitumor efficacy in breast cancer bearing mice with PEGylated MCs showing comparable tumor regression to folate-conjugated MCs. Conclusion: Evergreen nanoplatforms coloaded with monascus yellow pigments and RSV were effective for breast cancer treatment.

Schizophrenia is a mental disorder characterized by alterations in cognition, behavior and emotions. Oral olanzapine (OZ) administration is extensively metabolized (~up to 40% of the administrated dose). In addition, OZ is a P-glycoproteins substrate that impairs the blood–brain barrier (BBB) permeability. To direct OZ to the brain and to minimize its systemic side effects, the nasal pathway is recommended. OZ-loaded polymeric micelles nano-carriers were developed using suitable biodegradable excipients. The developed micelles were physicochemically investigated to assess their appropriateness for intranasal delivery and the potential of these carriers for OZ brain targeting. The selected formula will be examined in vivo for improving the anti-schizophrenic effects on a schizophrenia rat model. The binary mixture of P123/P407 has a low CMC (0.001326% w/v), which helps in maintaining the formed micelles’ stability upon dilution. The combination effect of P123, P407 and TPGS led to a decrease in micelle size, ranging between 37.5–47.55 nm and an increase in the EE% (ranging between 68.22–86.84%). The selected OZ–PM shows great stability expressed by a suitable negative charge zeta potential value (−15.11 ± 1.35 mV) and scattered non-aggregated spherical particles with a particle size range of 30–40 nm. OZ–PM maintains sustained drug release at the application site with no nasal cytotoxicity. In vivo administration of the selected OZ–PM formula reveals improved CNS targeting and anti-schizophrenia-related deficits after OZ nasal administration. Therefore, OZ–PM provided safe direct nose-to-brain transport of OZ after nasal administration with an efficient anti-schizophrenic effect.

Dental caries is an infectious oral disease caused by the presence of different bacteria in biofilms. Multidrug resistance (MDR) is a major challenge of dental caries treatment. Swabs were taken from 65 patients with dental caries in Makkah, Saudi Arabia. Swabs were cultivated on mitis salivarius agar and de Man, Rogosa, and Sharpe (MRS) agar. VITEK 2 was used for the identification of isolated bacteria. Antibiotic susceptibility testing of the isolated bacteria was performed using commercial antibiotic disks. Ulva lactuca was used as a reducing agent and cellulose source to create nanocellulose and Ag/cellulose nanocomposites. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction spectroscopy (XRD) were used to characterize nanocellulose and Ag/cellulose nanocomposites. The results showed that most bacterial isolates were Streptococcus spp., followed by Staphylococcus spp. on mitis salivarius media. Lactobacillus spp. and Corynebacterium group f-1 were the bacterial isolates on de Man, Rogosa, and Sharpe (MRS) media. The antibiotic susceptibility test revealed resistance rates of 77%, 93%, 0, 83%, 79%, and 79% against penicillin G, Augmentin, metronidazole, ampicillin, ciprofloxacin, and cotrimoxazole, respectively. Ag/cellulose nanocomposites and Ag/cellulose nanocomposites with fluoride were the most effective antibacterial agents. The aim of this work was to assess the antibacterial activity of Ag/cellulose nanocomposites with and without fluoride against bacteria isolated from the oral cavities of patients with dental caries. This study demonstrated that Ag/cellulose nanocomposites have antibacterial properties against multidrug-resistant bacteria that cause dental caries.