Incorporating sodium deoxycholate endorsed the buccal administration of avanafil to heighten the bioavailability and duration of action.

The highly effective phosphodiesterase type 5 inhibitor (avanafil; AVA) is routinely prescribed to treat erectile dysfunction. The drug has poor oral bioavailability and undergoes a significant first-pass metabolism. Therefore, altering AVA's solubility and choosing a different delivery method may boost its effectiveness. Nine different solid dispersion formulations utilizing polyvinylpyrrolidone (PVP) at three different ratios were prepared and characterized. The Box-Behnken design was employed to optimize AVA-buccal tablets. The pre-compression and post-compression characteristics of the tablets were assessed. The mucoadhesion strength of the optimized tablet was investigated using cow buccal mucosal tissue. In vivo performance of the optimized tablets was examined on human volunteers compared to the commercial tablets. PVP K90 at 2:1 drug to polymer ratio showed the highest solubilization capacity. The mucoadhesive polymer type and percentage and the mucopenetration enhancer percentage were significantly affect the mucoadhesion strength, tablet hardness, and the initial and cumulative AVA released from the prepared tablets. The optimized AVA-buccal tablet showed 4.96 folds increase in the mean residence time, higher plasma exposure, and an improvement in the relative bioavailability of AVA by 1076.27% compared with the commercial tablet. Therefore, a successful approach to deal with AVA first-pass metabolism and low bioavailability could be to employ buccal tablets containing a solubility-enhanced form of AVA.

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells.

Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells' penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon® 90 G: cholesterol molar ratio (PC: CH; X1, mole/mole), Phospholipon® 90 G: Tristearin weight ratio (PC: TS; X2, w/w) and apamin molar concentration (APA conc.; X3, mM) were considered as independent variables, while vesicle size (VS, Y1, nm) and zeta potential (ZP, Y2, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC50 value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of p53, bax and casp3 and downregulating bcl2. Furthermore, NF-κB activity was abolished while the expression of TNfα was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation.

Merging Experimental Design and Nanotechnology for the Development of Optimized Simvastatin Spanlastics: A Promising Combined Strategy for Augmenting the Suppression of Various Human Cancer Cells.

Simvastatin (SMV) is an antihyperlipidemic agent that has been investigated as a possible anti-cancer agent. An obstacle to malignant tumor therapy using drugs is the delivery of adequate levels to the cancer cells while minimizing side effects following their systemic administration. To circumvent this challenge, the researchers directed towards the field of nanotechnology to benefit from the nano-size of the formulation in passively targeting the tumor cells. Thus, our study aimed at investigating the potential of a combined mixture-process variable design for optimization of SMV spanlastics (SMV-SPNs) with minimized particle size and maximized zeta potential to enhance the anticancer activity of the drug. The study investigated the effects of Span® 20 and Tween® 80 as mixture components and sonication time as a process variable on particle size, polydispersity index, and zeta potential as responses. SPNs were prepared using an ethanol injection method. Combining the predicted optimized variables' levels is supposed to achieve the set goals with a desirability of 0.821. The optimized spanlastics exhibited a measured globule size of 128.50 nm, PDI of 0.329, and ZP of -29.11 mV. The percentage relative error between predicted responses and the observed ones were less than 5% for the three responses, indicating the optimization technique credibility. A significant improvement in the cytotoxicity of the optimized formulation against three different cancerous cell lines was observed in comparison with SMV. The inhibitory concentration (IC50) values of MCF-7, HCT-116, and HEPG2 were found to be 0.89, 0.39, and 0.06 µM at 24 h incubation. The enhanced cytotoxicity could be assigned to the possible improved permeation and preferential build-up within the cancerous cells by virtue of the minimized size. These findings imply that SMV-SPNs could be an ideal strategy to combat cancer.

Wasp venom peptide improves the proapoptotic activity of alendronate sodium in A549 lung cancer cells.

BACKGROUND: Lung cancer in men and women is considered the leading cause for cancer-related mortality worldwide. Anti-cancer peptides represent a potential untapped reservoir of effective cancer therapy. METHODOLOGY: Box-Behnken response surface design was applied for formulating Alendronate sodium (ALS)-mastoparan peptide (MP) nanoconjugates using Design-Expert software. The optimization process aimed at minimizing the size of the prepared ALS-MP nanoconjugates. ALS-MP nanoconjugates' particle size, encapsulation efficiency and the release profile were determined. Cytotoxicity, cell cycle, annexin V staining and caspase 3 analyses on A549 cells were carried out for the optimized formula. RESULTS: The results revealed that the optimized formula was of 134.91±5.1 nm particle size. The novel ALS-MP demonstrated the lowest IC50 (1.3 ± 0.34 µM) in comparison to ALS-Raw (37.6 ± 1.79 µM). Thus, the results indicated that when optimized ALS-MP nanoconjugate was used, the IC50 of ALS was also reduced by half. Cell cycle analysis demonstrated a significantly higher percentage of cells in the G2-M phase following the treatment with optimized ALS-MP nanoconjugates. CONCLUSION: The optimized ALS-MP formula had significantly improved the parameters related to the cytotoxic activity towards A549 cells, compared to control, MP and ALS-Raw.

Green Nanoemulsion Stabilized by In Situ Self-Assembled Natural Oil/Native Cyclodextrin Complexes: An Eco-Friendly Approach for Enhancing Anticancer Activity of Costunolide against Lung Cancer Cells.

Lung cancer is the second-most deadly malignancy worldwide, of which smoking is considered a major risk factor and causes 75-80% of lung cancer-related deaths. Costunolide (CTD) extracted from plant species Saussurea, Aucklandia, and Inula exhibits potent anticancer properties, specifically in lung cancer and leukemia. Several nanoemulsions were prepared and optimized using a three-factor Box-Behnken experimental design. The optimized green nanoemulsion (GNE) showed a vesicle size of 199.56 nm. The IC50 values revealed that A549 cells were significantly more sensitive to the optimized CTD formula than the plain formula and raw CTD. A cell cycle analysis revealed that the optimized CTD formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with the CTD formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to the plain formula and CTD raw. In terms of the inflammatory markers, the optimized formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and raw drug only. Overall, the findings from the study proved that a CTD GNE formulation could be a promising therapeutic approach for the treatment of lung cancer.

Transdermal Film Loaded with Avanafil Ultra-deformable Nanovesicles to Enhance its Percutaneous Absorption and Bioavailability.

The in vitro dissolution of Avanafil (AVA) is the rate-limiting step for its bioavailability. Also, it undergoes the first-pass metabolism, and its absorption is altered significantly in the presence of food. So, our study aimed to overcome the previous hurdles and improve the AVA bioavailability by its incorporation in the ultra-deformable nanovesicles, transfersomes (TRF), then loading these nanovesicles in transdermal films. The AVA-loaded TRF formulation was optimized using Draper-Lin small composite design (D-LSCD). The optimized AVA-loaded TRF was evaluated for quality attributes and assessed for skin permeation using a fluorescence laser microscope and for pharmacokinetic parameters after topical application on the rats. The optimized AVA-loaded TRF showed a vesicle size of 97.75 nm, a zeta potential of -28.83 mV, and entrapment efficiency of 95.14% with good deformability and release profile. The intense discoloration in the deep skin layers of the rats indicated the permeation efficiency of AVA-loaded TRF films. The pharmacokinetic parameters specified the augmented absorption extent with Cmax of 254.66 ± 8.02 ng/mlversus 70.33 ± 3.05 ng/ml which reflected on the AUC0-inf that has a value of 2050.45 ± 159.14 ng/ml h versus 497.34 ± 102.61 ng/ml h for the optimized AVA-loaded TRF film and raw AVA-loaded film, respectively. These promising results wide open the field for broader clinical application of this alternative delivery pathway for superior bioavailability, efficacy, and patient compliance and satisfaction.

Development of an Icariin-Loaded Bilosome-Melittin Formulation with Improved Anticancer Activity against Cancerous Pancreatic Cells.

Pancreatic cancer currently represents a severe issue for the entire world. Therefore, much effort has been made to develop an effective treatment against it. Emerging evidence has shown that icariin, a flavonoid glycoside, is an effective anti-pancreatic cancer drug. Melittin, as a natural active biomolecule, has also shown to possess anticancer activities. In the present study, with the aim to increase its effectiveness against cancerous cells, icariin-loaded bilosome-melittin (ICA-BM) was developed. For the selection of an optimized ICA-BM, an experimental design was implemented, which provided an optimized formulation with a particle size equal to 158.4 nm. After estimation of the release pattern, the anti-pancreatic cancer efficacy of this new formulation was evaluated. The MTT assay was employed for the determination of half maximal inhibitory concentration (IC50), providing smaller IC50 for ICA-BM (2.79 ± 0.2 µM) compared to blank-BM and ICA-Raw (free drug) against PNAC1, a human pancreatic cancer cell line isolated from a pancreatic carcinoma of ductal cell origin. Additionally, cell cycle analysis for ICA-BM demonstrated cell arrest at the S-phase and pre-G1 phase, which indicated a pro-apoptotic behavior of the new developed formulation. The pro-apoptotic and anti-proliferative activity of the optimized ICA-BM against PNAC1 cells was also demonstrated through annexin V staining as well as estimation of caspase-3 and p53 protein levels. It can be concluded that the optimized ICA-BM formulation significantly improved the efficacy of icariin against cancerous pancreatic cells.