Breast cancer is a dangerous type of cancer in women. Quercetin (QRT), a naturally occurring flavonoid, has wide biological effects including antioxidant, anticarcinogenic, anti-inflammatory, antiallergic, and antiviral activities. The anticancer activity is considered the most valuable effect of QRT against several types of cancer, including prostate, liver, lung, colon, and breast cancer. Scorpion venom peptides (SV) has been found to induce apoptosis and aggravate cancer cells, making it a promising anticancer agent. QRT, SV, and Phospholipon^® 90H (PL) were incorporated in a nano-based delivery platform to assess QRT’s cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human breast cancer cells MCF-7. Several nanovesicles were prepared and optimized, using four-factor Box–Behnken, in an experimental design. The optimized phytosomes showed vesicle size and zeta potential values of 116.9 nm and 31.5 mV, respectively. The IC50 values revealed that MCF-7 cells were significantly more sensitive to the optimized QRT formula than the plain formula and raw QRT. Cell cycle analysis revealed that optimized QRT formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with QRT formula significantly increased caspase-9, Bax, Bcl-2, and p53 mRNA expression, compared with the plain formula and QRT. In terms of the inflammatory markers, the QRT formula significantly reduced the activity of TNF-α and NF-κB, in comparison with the plain formula and QRT only. Overall, the findings from the study proved that a QRT formulation could be a promising therapeutic approach for the treatment of breast cancer.

In oral administration systems, mucoadhesive polymers are crucial for drug localization and target-specific activities. The current work focuses on the application of thiolated xanthan gum (TXG) to develop and characterize a novel mucoadhesive nanocrystal (NC) system of simvastatin (SIM). Preparation of SIM-NC was optimized using response surface methodology (RSM) coupled with statistical applications. The concentration of Pluronic F-127 and vacuum pressure were optimized by central composite design. Based on this desirable approach, the prerequisites of the optimum formulation can be achieved by a formulation having 92.568 mg of F-127 and 77.85 mbar vacuum pressure to result in EE of 88.8747% and PS of 0.137.835 nm. An optimized formulation was prepared with the above conditions along with xanthan gum (XG) and TXG and various parameters were evaluated. A formulation containing TXG showed 98.25% of SIM at the end of 96 h. Regarding the mucoadhesion potential evaluated by measuring zeta potential, TXG-SIM-NC shoed the maximum zeta potential of 16,455.8 ± 869 mV at the end of 6 h. The cell viability percentage of TXG-SIM-NC (52.54 ± 3.4% with concentration of 50 µg/mL) was less than the plain SIM, with XG-SIM-NC showing the highest cytotoxicity on HSC-3 cells. In vivo pharmacokinetic studies confirm the enhanced bioavailability of formulated mucoadhesive systems of SIM-NC, with TXG-SIM-NC exhibiting the maximum.

Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple cider vinegar (APCV) and loaded with minoxidil (MX) in order to enhance drug solubilization and permeation through skin. A distance coordinate exchange quadratic mixture design was used to optimize the proposed nanoemulsion. Span 20 and Tween 20 mixtures were used as the surfactant, and Transcutol was used as the co-surfactant. The developed formulations were characterized for their droplet size, minoxidil steady-state flux (MX Jss) and minimum inhibitory concentration (MIC) against Propionibacterium acnes. The optimized MX-GO-APCV nanoemulsion had a droplet size of 110 nm, MX Jss of 3 μg/cm² h, and MIC of 0.275 μg/mL. The optimized formulation acquired the highest ex vivo skin permeation parameters compared to MX aqueous dispersion, and varying formulations lacked one or more components of the proposed nanoemulsion. GO and APCV in the optimized formulation had a synergistic, enhancing activity on the MX permeation across the skin membrane, and the percent permeated increased from 12.7% to 41.6%. Finally, the MX-GO-APCV nanoemulsion followed the Korsmeyer–Peppas model of diffusion, and the value of the release exponent (n) obtained for the formulations was found to be 1.0124, implying that the MX permeation followed Super case II transport. These results demonstrate that the MX-GO-APCV nanoemulsion formulation could be useful in promoting MX activity in treating alopecia areata.

Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRG_K) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

Doxorubicin (DOX), a commonly utilized anthracycline antibiotic, suffers deleterious side effects such as cardiotoxicity. Mokko lactone (ML) is a naturally occurring guainolide sesquiterpene with established antioxidant and anti-inflammatory actions. This study aimed at investigating the protective effects of ML in a DOX-induced cardiotoxicity model in rats. Our results indicated that ML exerted protection against cardiotoxicity induced by DOX as indicated by ameliorating the rise in serum troponin and creatine kinase-MB levels and lactate dehydrogenase activity. Histological assessment showed that ML provided protection against pathological alterations in heart architecture. Furthermore, treatment with ML significantly ameliorated DOX-induced accumulation of malondialdehyde and protein carbonyl, depletion of glutathione, and exhaustion of superoxide dismutase and catalase. ML’s antioxidant effects were accompanied by increased nuclear translocation of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, ML exhibited significant anti-inflammatory activities as evidenced by lowered nuclear factor κB, interleukin-6, and tumor necrosis factor-α expression. ML also caused significant antiapoptotic actions manifested by modulation in mRNA expression of Bax, Bcl-2, and caspase-3. This suggests that ML prevents heart injury induced by DOX via its antioxidant, anti-inflammatory, and antiapoptotic activities.