Designing and fabrication of colloidal nano-phytosomes with gamma-oryzanol and phosphatidylcholine for encapsulation and delivery of polyphenol-rich extract from pomegranate peel.

Nano-carriers are well-known delivery systems to encapsulate different bioactive compounds and extracts. Such nano-systems are used in various food and drug areas to protect active ingredients, increase bioavailability, control the release, and deliver bioactive substances. This study aimed to design and fabricate a stable colloidal nano-delivery system to better preserve the antioxidant properties of pomegranate peel extract (PPE) and protect its sustained release in a gastrointestinal model. To achieve this goal, a nano-phytosomal system was fabricated with plant-based, cost-effective, and food-grade compounds, i.e., phosphatidylcholine (PC) and gamma-oryzanol (GO) for encapsulation of PPE. To fabricate the nano-phytosomes, thin film hydration/sonication method was used. The parameters of particle size, zeta potential, polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) were investigated to evaluate the efficiency of the produced nano-system. In summary, the size, zeta potential, PDI, LC, and EE of homogenous spherical PC-GO-PPE nano-phytosomes (NPs) in the ratio of 8:2:2 % w/w were achieved as 60.61 ± 0.81 nm, -32.24 ± 0.84 mV, 0.19 ± 0.01, 19.13 ± 0.30 %, and 95.66 ± 1.52 %, respectively. Also, the structure of NPs was approved by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). The optimized NPs were stable during one month of storage at 4 °C, and changes in the size of particles and PPE retention rate were insignificant (p > 0.05). The nano-encapsulation of PPE significantly decreased the loss of its antioxidant activity during one month of storage at 4 °C. The optimized NPs exhibited prolonged and sustained release of PPE in a gastrointestinal model, so that after 2 h in simulated gastric fluid (SGF) and 4 h in simulated intestinal fluid (SIF), 22.66 ± 2.51 % and 69.33 ± 4.50 % of initially loaded PPE was released, respectively. Optimized NPs had considerable cytotoxicity against the Michigan Cancer Foundation-7 cell line (MCF7) (IC50 = 103 µg/ml), but not against Human Foreskin Fibroblast cell line (HFF-2) (IC50 = 453 µg/ml). In conclusion, spherical PC-GO-PPE NPs were identified as a promising delivery system to efficiently encapsulate PPE, as well as protect and preserve its bioactivity, including antioxidant and cytotoxicity against cancer cell line.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

Development and in vivo evaluation of therapeutic phytosomes for alleviation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with progressive articular damage, functional loss and comorbidity. Conventional RA therapy requires frequent dosing and prolonged use, and usually results in poor efficacy and severe toxicity. In the current study, for the first time, we describe a combination strategy using phytosomes co-loaded with curcumin (CUR) and leflunomide (LEF) to improve the clinical outcomes of RA therapy. Exploiting 23 factorial design, various compositions of CUR and LEF co-loaded phytosomes (CUR/LEF-phytosomes) were successfully prepared and were extensively characterized (e.g., particle size, zeta potential, drugs encapsulation efficiency, morphology, DSC, FTIR and release kinetics). The optimal CUR/LEF-loaded phytosomes (F2) demonstrated high stability and spherical morphology with a particle size of ca. 760 nm and negative zeta potential value of - 55.7, high entrapment for both drugs, and sustained release profile of the entrapped medications. In vivo, oral administration of the CUR/LEF-phytosomes (F2) in arthritic rats resulted in significant reduction of paw swelling and inflammatory markers, compared to the free drugs and their physical mixture. Histopathological examination revealed significant improvement in phytosomes-treated animal group with no signs of arthritis. CUR/LEF-loaded phytosomes provide an auspicious strategy for alleviation of RA.

Effects of green tea phytosome on growth performance and intestinal integrity under coccidiosis infection challenge in broilers.

This research examined the effects of feeding phytosomal green tea on broilers infected with coccidia. To provide phytosome, green tea extract was loaded into soy lecithin. Groups of chicks included uninfected and untreated control (NC), infected and untreated control (PC), infected and treated with salinomycin control (SC), infected and treated with 300 and 400 mL of green tea extract (GTE300, GTE400), infected and treated with 200, 300, 400 and 500 mL of green tea phytosome (GTP200, GTP300, GTP400, and GTP500). At 14-days posthatch, chickens were orally gavaged, except the NC group with a coccidia vaccine 30 times larger than the approved dose. Body weight (BW), feed intake (FI), and feed conversion ratio (FCR) were determined at 7, 14, 20, 28, 35, and 42 d. The characteristics of the carcass, internal organs and intestinal morphology were assessed on d 42. Applying overdose of coccidiosis vaccine showed experimental Eimeria infection, led to decrease in FI and BW, and increased FCR compared to PC group (P < 0.001). Meanwhile salinomycin, green tea extract, and green tea phytosome compensated the negative effects of Eimeria infection on growth performance. The treatments did not affect carcass, breast, and thigh relative weights. Interestingly, abdominal fat percent was significantly lower in chickens fed GTP300, GTP400, and GTP500 than in those fed GTE300, GTE300, and GTP200 (P < 0.0001). In comparison to the basal diet plus green tea extract forms and NC groups, the PC group increased the relative weights of the liver, spleen, bursa, and pancreas (P < 0.05). The highest values of villus height and villus height to crypt ratio were obtained in duodenum, jejunum and ileum in GTP300 group (P < 0.0001), while, villi diameter in duodenum and ileum decreased the most in GTP300 and GTP500, respectively (P < 0.0001). Consequently, as natural anticoccidial drug delivery systems, 300 mL of green tea phytosome can be introduced as the optimal dose to maximize the benefits of phytosome for intestinal integrity and reduce the consumption of green tea extract.

The combination of polyphenols and phospholipids as an efficient platform for delivery of natural products.

Although nature is a rich source of potential drugs and drug leads, the widespread application of natural products (NPs) is limited due to their poor absorption when administered orally. A strategy of using phytosome has emerged as a promising technique to increase the bioavailability of NPs. Here, a comprehensive computational investigation is performed to explore the nature of interactions in the formation of phytosomes between phosphatidylcholine (PC) and a series of polyphenols (PP), including epigallocatechin-3-gallate (Eg), luteolin (Lu), quercetin (Qu), and resveratrol (Re). Our quantum mechanical calculation revealed that the intermolecular hydrogen bonds (HBs) of phosphate and glycerol parts of PC with the polyphenol compounds are the main driving force in the formation of phytosomes. The strongest HB (with energy HB = - 108.718 kJ/mol) is formed between the Eg molecule and PC. This hydrogen bond results from the flexible structure of the drug which along with several van der Waals (vdW) interactions, makes Eg-PC the most stable complex (adsorption energy = - 164.93 kJ/mol). Energy decomposition analysis confirms that the electrostatic interactions (hydrogen bond and dipole-diploe interactions) have a major contribution to the stabilization of the studied complexes. The obtained results from the molecular dynamics simulation revealed that the formation of phytosomes varies depending on the type of polyphenol. It is found that the intermolecular hydrogen bonds between PP and PC are a key factor in the behavior of the PP-PC complex in the self-aggregation of phytosome. In Eg-PC, Lu-PC, and Qu-PC systems, the formation of strong hydrogen bonds (HBCP < 0 and ∇2ρBCP > 0) between PP and PC protects the PP-PC complexes from degradation. The steered molecular dynamics simulation results have a good agreement with experimental data and confirm that the phytosome platform facilitates the penetration of PP compounds into the membrane cells.

Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

An Exploration of Herbal Extracts Loaded Phyto-phospholipid Complexes (Phytosomes) Against Polycystic Ovarian Syndrome: Formulation Considerations.

BACKGROUND: Herbal preparations with low oral bioavailability have a fast first-pass metabolism in the gut and liver. To offset these effects, a method to improve absorption and, as a result, bioavailability must be devised. OBJECTIVE: The goal of this study was to design, develop, and assess the in vivo toxicity of polyherbal phytosomes for ovarian cyst therapy. METHODS: Using antisolvent and rotational evaporation procedures, phytosomes containing phosphatidylcholine and a combination of herbal extracts (Saraca asoca, Bauhinia variegata, and Commiphora mukul) were synthesized. For a blend of Saraca asoca, Bauhinia variegata, and Commiphora mukul, Fourier-transform infrared spectroscopy (FTIR), preformulation investigations, qualitative phytochemical screening, and UV spectrophotometric tests were conducted. Scanning electron microscopy (SEM), zeta potential, ex vivo release, and in vivo toxicological investigations were used to examine phytosomes. RESULTS: FTIR studies suggested no changes in descriptive peaks in raw and extracted herbs, although the intensity of peaks was slightly reduced. Zeta potential values between -20.4 mV to - 29.6 mV suggested stable phytosomes with an accepted particle size range. Percentage yield and entrapment efficiency were directly correlated to the amount of phospholipid used. Ex vivo studies suggested that the phytosomes with low content of phospholipids showed good permeation profiles. There was no difference in clinical indications between the extract-loaded phytosomes group and the free extract group in in vivo toxicological or histopathological examinations. CONCLUSION: The findings of current research work suggested that the optimized phytosomes based drug delivery containing herbal extracts as bioenhancers has the potential to improve the bioavailability of hydrophobic extracts.

Phytosomes: A promising delivery system for anticancer agents by using phytochemicals in cancer therapy.

Plant extracts have been shown to be effective in treating a variety of ailments; however their hydrophilic nature and unique chemical structure have caused significant hurdles due to their low bioavailability. Phytosomes technology is used to improve the absorption of phytoconstituents that are difficult to absorb. Among the leading deaths in the society is malignancy. The aforementioned consumes remained a big issue for modern chemotherapy since it has yet to be treated in an efficient manner. The goal of this study is to outline the most recent research on the potential use of phytosome complexes for cancer therapy, as well as the formulation processes and mechanism of transportation through phytosomes.Nanotechnology has paved the way for cancer therapy by altering key features of medications and their carriers. Novel drug delivery systems are used to transfer antitumor drugs to the particular site via different nanostructures. Among several unique drug delivery systems, phytosomes are a creative way to transfer phytoactive compounds to the site of action, and several phytosomes formulations are now being used in clinical settings. Phytoconstituents' anti-cancer activities are increased by phytosomal formulations.