Piceatannol-Loaded Bilosome-Stabilized Zein Protein Exhibits Enhanced Cytostatic and Apoptotic Activities in Lung Cancer Cells

Abstract

Piceatannol (PIC) is a naturally occurring polyphenolic stilbene, and it has pleiotropic pharmacological properties. Moreover, PIC has cytotoxic actions among various cancer cells. In this work, preparations of PIC-loaded bilosome–zein (PIC-BZ) were designed, formulated, and characterized, and the optimized PIC-BZ cytotoxic activities, measured as half maximal inhibitory concentration (IC50), against lung cancer cell line was investigated. Box–Behnken design was utilized in order to examine the effect of preparation factors on drug entrapment and particle size. PIC-BZ showed a spherical shape after optimization, and its particle size was determined as 157.45 ± 1.62 nm. Moreover, the efficiency of drug entrapment was found as 93.14 ± 2.15%. The cytotoxic activity evaluation revealed that the adjusted formulation, which is PIC-BZ formula, showed a substantially smaller IC50 versus A549 cells. Cell cycle analysis showed accumulation of cells in the G2-M phase. Moreover, it showed in the sub-G1 phase, a rise of cell fraction suggestion apoptotic improving activity. Increased early and late phases of apoptosis were demonstrated by staining of cells with annexin V. Furthermore, the cellular caspase-3 protein expression was significantly raised by PIC-BZ. In addition, the wound healing experiment confirmed the results. To conclude, compared to pure PIC, PIC-BZ demonstrated a higher cell death-inducing activity against A549 cells.

Development of a Novel Bilosomal System for Improved Oral Bioavailability of Sertraline Hydrochloride: Formulation Design, In Vitro Characterization, and Ex Vivo and In Vivo Studies

“…All the studied responses were tested for fitting to main effect, 2FI and 3FI models. The best fit model for elucidating the effect of the independent variables on responses was the one with the highest predicted R 2 and the lowest PRESS (predicted residual error sum of squares) [47,48]. Moreover, adjusted R 2 and predicted R 2 for the selected model should be within approximately 0.2 of each other to be in a reasonable agreement [13].…”

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

“…A modified thin-film hydration method was employed to formulate ICA-BM, as previously described [15]. Briefly, ICA (20 mg), cholesterol, and Span 20 (amount indicated in the experiment's design) were dissolved in 10 mL of chloroform.…”

“…The rate of release for ICA from BM was analyzed as per the previously reported methods [15,49]. For this purpose, 0.1 M PBS at pH 7.4 containing Tween 80 (0.1%) to maintain the sink condition was used.…”

“…As natural detergents are part of this nanocarrier, bile salts are able to increase the permeability of drug molecules across biological barriers, also improving drug bioavailability at desired sites. Furthermore, the presence of bile salts in the lipid bilayer of a nanocarrier system protects the entrapped drug from the various gastrointestinal fluids [15]. Based on their multiple activities, bilosomes have been used as a drug delivery system in numerous studies [16][17][18].…”

Development and evaluation of luteolin loaded pegylated bilosome: optimization, in vitro characterization, and cytotoxicity study

“…The lipid-based nanocarrier systems have been used to enhance the solubility as well as therapeutic activity. These systems include eplerenone nanostructured lipid carriers (NLCs) (Abd-Elhakeem et al., 2021 ), rosuvastatin liposomes (Ahmed, 2020 ), lovastatin hybrid liposome (Romana et al., 2020 ), glycyrrhizic acid and cisplatin nanoliposomes (Hatami et al., 2020 ), Fumaria officinalis niosomes (Raafat & El-Zahaby, 2020 ), apigenin, piceatannol bilosomes (Alhakamy et al., 2021 ; Zafar et al., 2021 ), and olmesartan medoxomil pegylated bilosomes (PG-BLs) (Albash et al., 2019 ). Among them, PG-BLs are the new approach for the improvement of the therapeutic efficacy of the poorly soluble drugs.…”