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.

Food-grade phytosome vesicles for nanoencapsulation of labile C-glucosylated xanthones and dihydrochalcones present in a plant extract matrix-Effect of process conditions and stability assessment.

Phytosomes consist of a phytochemical bound to the hydrophilic choline head of a phospholipid. Their use in food products is gaining interest. However, literature on the use of food-grade solvents, crude plant extracts as opposed to pure compounds, and unrefined phospholipids to prepare phytosomes is limited. Furthermore, studies on compound stability are lacking. This study aimed to develop nano-phytosome vesicles prepared from inexpensive food-grade ingredients to improve the stability of polyphenolic compounds. Cyclopia subternata extract (CSE) was selected as a source of phenolic compounds. It contains substantial quantities of C-glucosyl xanthones, benzophenones, and dihydrochalcones, compounds largely neglected to date. The effect of process conditions on the complexation of CSE polyphenols with minimally refined food-grade fat-free soybean lecithin (PC) was studied. The PC:CSE ratio, sonication time, and reaction temperature were varied. This resulted in phytosomes ranging in vesicle size (113.7-312.7 nm), polydispersity index (0.31-0.48), and zeta potential (-55.0 to -38.9 mV). Variation was also observed in the yield (93.5%-96.0%), encapsulation efficiency (3.7%-79.0%), and loading capacity (LC, 1.3%-14.7%). Vesicle size and LC could be tailored by adjusting the sonication time and PC:CSE ratio, respectively. Chemical interaction between the lipid and the phenolic compounds was confirmed with nuclear magnetic resonance. Phytosomal formulation protected the compounds against degradation when freeze-dried samples were stored at 25 and 40°C for 6 months at low relative humidity. The study provided valuable information on the importance of specific process parameters in producing food-grade phytosomes with improved phenolic stability.

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.

Nano-platform Strategies of Herbal Components for the management of Rheumatoid Arthritis: A Review on the Battle for Next-Generation Formulations.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that initially affects small joints and then spreads to the bigger joints. It also affects other organs of the body such as the lungs, eyes, kidneys, heart, and skin. In RA, there is destruction of cartilage and joints, and ligaments and tendons become brittle. Damage to the joints leads to abnormalities and bone degradation, which may be quite painful for the patient. METHOD: The nano-carriers such as liposomes, phytosomes, nanoparticles, microcapsules, and niosomes are developed to deliver the encapsulated phytoconstituents to targeted sites for the better management of RA. RESULTS: The phytoconstituents loaded nano-carriers have been used in order to increase bioavailability, stability and reduce the dose of an active compound. In one study, the curcumin-loaded phytosomes increase the bioavailability of curcumin and also provides relief from RA symptoms. The drug-loaded nano-carriers are the better option for the management of RA. CONCLUSION: In conclusion, there are many anti-arthritic herbal and synthetic medicine available in the market that are currently used in the treatment of RA. However, chronic use of these medications may result in a variety of side effects. Because therapy for RA is frequently necessary for the rest of ones life. The use of natural products may be a better option for RA management. These phytoconstituents, however, have several disadvantages, including limited bioavailability, low stability, and the need for a greater dosage. These problems can be rectified by using nano-technology.

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.

Development of Pegylated Nano-Phytosome Formulation with Oleuropein and Rutin to Compare Anti-Colonic Cancer Activity with Olea Europaea Leaves Extract.

Olive leaf extract is a valuable source of phenolic compounds; primarily, oleuropein (major component) and rutin. This natural olive leaf extract has potential use as a therapeutic agent for cancer treatment. However, its clinical application is hindered by poor pharmacokinetics and low stability. To overcome these limitations, this study aimed to enhance the anticancer activity and stability of oleuropein and rutin by loading them into PEGylated Nano-phytosomes. The developed PEGylated Nano-phytosomes exhibited favorable characteristics in terms of size, charge, and stability. Notably, the anticolonic cancer activity of the Pegylated Nano-phytosomes loaded with oleuropein (IC50=0.14 µM) and rutin (IC50=0.44 µM) surpassed that of pure oleuropein and rutin alone. This outcome highlights the advantageous impact of Nano-phytosomes to augment the anticancer potential of oleuropein and rutin. These results present a promising pathway for the future development of oleuropein and rutin Nano-phytosomes as effective options for passive tumor-targeted therapy, given their improved stability and efficacy.

Different Types of Naturally based Drug Delivery Carriers: An Explanation and Expression of Some Anti-cancer Effects.

Cancer remains one of the leading causes of death worldwide and a major impediment to increasing life expectancy. However, survival rates with average standard cancer treatment strategies have not significantly improved in recent decades, with tumor metastasis, adverse drug reactions, and drug resistance still posing major challenges. Replacement therapies are essential for treating this terrible disease. Recently, there has been a dramatic increase in the use of phytochemical-derived conjugated chemotherapeutic agents due to their biocompatibility, low cytotoxicity, low resistance, and dynamic physiochemical properties that distinguish normal cells in treating various types of cancer. The use of plant-based carriers has many advantages, such as the availability of raw materials, lower cost, lower toxicity in most cases, and greater compatibility with the body's structure compared to chemical and mineral types of carriers. Unfortunately, several challenges complicate the efficient administration of herbal medicines, including physicochemical disadvantages such as poor solubility and instability, and pharmacokinetic challenges such as poor absorption and low bioavailability that can cause problems in clinical trials. Novel delivery systems such as liposomes, phytosomes, nanoparticles, and nanocapsules are more suitable as delivery systems for phytomedicinal components compared to conventional systems. The use of these delivery systems can improve bioavailability, pharmacological activity, prolonged delivery, and provide physical and chemical stability that increases half-life. This article discusses different types of phytocompounds used in cancer treatment.

Exploring the Synergistic Effect of Bergamot Essential Oil with Spironolactone Loaded Nano-Phytosomes for Treatment of Acne Vulgaris: In Vitro Optimization, In Silico Studies, and Clinical Evaluation.

The foremost target of the current work was to formulate and optimize a novel bergamot essential oil (BEO) loaded nano-phytosomes (NPs) and then combine it with spironolactone (SP) in order to clinically compare the efficiency of both formulations against acne vulgaris. The BEO-loaded NPs formulations were fabricated by the thin-film hydration and optimized by 32 factorial design. NPs' assessments were conducted by measuring entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In addition, the selected BEO-NPs formulation was further combined with SP and then examined for morphology employing transmission electron microscopy and three months storage stability. Both BEO-loaded NPs selected formula and its combination with SP (BEO-NPs-SP) were investigated clinically for their effect against acne vulgaris after an appropriate in silico study. The optimum BEO-NPs-SP showed PS of 300.40 ± 22.56 nm, PDI of 0.571 ± 0.16, EE% of 87.89 ± 4.14%, and an acceptable ZP value of -29.7 ± 1.54 mV. Molecular modeling simulations showed the beneficial role of BEO constituents as supportive/connecting platforms for favored anchoring of SP on the Phosphatidylcholine (PC) interface. Clinical studies revealed significant improvement in the therapeutic response of BEO-loaded NPs that were combined with SP over BEO-NPs alone. In conclusion, the results proved the ability to utilize NPs as a successful nanovesicle for topical BEO delivery as well as the superior synergistic effect when combined with SP in combating acne vulgaris.

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.

Preparation, Characterization, Wound Healing, and Cytotoxicity Assay of PEGylated Nanophytosomes Loaded with 6-Gingerol.

BACKGROUND: Nutrients are widely used for treating illnesses in traditional medicine. Ginger has long been used in folk medicine to treat motion sickness and other minor health disorders. Chronic non-healing wounds might elicit an inflammation response and cancerous mutation. Few clinical studies have investigated 6-gingerol's wound-healing activity due to its poor pharmacokinetic properties. However, nanotechnology can deliver 6-gingerol while possibly enhancing these properties. Our study aimed to develop a nanophytosome system loaded with 6-gingerol molecules to investigate the delivery system's influence on wound healing and anti-cancer activities. METHODS: We adopted the thin-film hydration method to synthesize nanophytosomes. We used lipids in a ratio of 70:25:5 for DOPC(dioleoyl-sn-glycero-3-phosphocholine): cholesterol: DSPE/PEG2000, respectively. We loaded the 6-gingerol molecules in a concentration of 1.67 mg/mL and achieved size reduction via the extrusion technique. We determined cytotoxicity using lung, breast, and pancreatic cancer cell lines. We performed gene expression of inflammation markers and cytokines according to international protocols. RESULTS: The synthesized nanophytosome particle sizes were 150.16 ± 1.65, the total charge was -13.36 ± 1.266, and the polydispersity index was 0.060 ± 0.050. Transmission electron microscopy determined the synthesized particles' spherical shape and uniform size. The encapsulation efficiency was 34.54% ± 0.035. Our biological tests showed that 6-gingerol nanophytosomes displayed selective antiproliferative activity, considerable downregulation of inflammatory markers and cytokines, and an enhanced wound-healing process. CONCLUSIONS: Our results confirm the anti-cancer activity of PEGylated nanophytosome 6-gingerol, with superior activity exhibited in accelerating wound healing.

Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy.

Saudi Arabia has a rich culture of folk medicines and three such common herbs used by Saudi people for therapy of breast cancer are Turmeric (Kurkum) Curcuma longa, Chamomile (Babunaj) Matricaria chamomilla, and Aswaghantha (Aswaghadh) Withania somnifera. Hence, the present study aims to develop a polyherbal phytosome formulation by thin film hydration technique with a synergistic anti-cancer effect for the treatment of breast cancer. The phytosomes were standardized for their phytoconstituents by HPTLC and showed the best optimal properties with a mean vesicle diameter of less than 200 nm, zeta potential in the range of -24.43 to -35.70 mV, and relatively integrated structure with fairly uniform size on TEM. The in vitro MTT assay on MCF-7 breast cancer cell lines and MDA MB 231 breast adenocarcinoma cell lines was carried out. MTT assay on MCF-7 breast cancer cell lines indicated that plant extract-loaded phytosomes exhibited enhanced cytotoxic effects at IC50 values. of 55, 50, 45, 52, 42, 44, and 20 µg/mL compared to the extracts of C. longa, M. chamomilla, W. somnifera, and their combined extracts (80, 82, 74, 60, 70, 60, and 35 µg/mL respectively). Moreover, intracellular reactive oxygen species production was found to be higher for phytosomes treated cells at respective IC50 concentrations when compared to extracts. Overall, the developed polyherbal phytosomes were found to be effective and afford synergistic effects for breast cancer therapy.

Phytosomal tripterine with selenium modification attenuates the cytotoxicity and restrains the inflammatory evolution via inhibiting NLRP3 inflammasome activation and pyroptosis.

Inflammation mediates a variety of physiological and pathological events, prompting an importance of inflammation management for prevention and treatment of inflammatory diseases. This study formulated tripterine (Tri) into selenized phytosomes in an attempt to attenuate its cytotoxicity and potentiate its inflammation-regulating effect with selenium. Tri-loaded phytosomes (Tri-PTs) with selenium modification were prepared by a melting-hydration followed by in situ reduction technique. Then, selenized Tri-PTs (Se@Tri-PTs) were characterized by particle size, entrapment efficiency, and transmission electron microscope. The in vitro drug release and cellular uptake were performed to examine the formulation performance of Se@Tri-PTs. The cytotoxicity and anti-inflammatory efficacy through inhibiting NLRP3 inflammasome activation and pyroptosis were appreciated in murine J774A.1 macrophage cell line, respectively. The resultant Se@Tri-PTs presented a particle size of 125 nm around. Se@Tri-PTs exhibited attenuated cytotoxicity and improved cellular uptake in macrophages compared with free Tri or Tri-PTs. Also, Se@Tri-PTs inhibited the releases of caspase-1p20 and mature IL-1ß, resulting in restriction of NLRP3 inflammasome activation that inhibits the formation of GSDMD-NT whereby to initiate pyroptosis. Altogether, our findings suggest that Se@Tri-PTs can inhibit inflammatory response by regulating the NLRP3/caspase-1 pathway, which in turn reduces pyroptosis via suppressing the cleavage of GSDMD.

Bioactive Loaded Novel Nano-Formulations for Targeted Drug Delivery and Their Therapeutic Potential.

Plant-based medicines have received a lot of attention in recent years. Such medicines have been employed to treat medical conditions since ancient times, and in those times only the observed symptoms were used to determine dose accuracy, dose efficacy, and therapy. Rather than novel formulations, the current research work on plant-based medicines has mostly concentrated on medicinal active phytoconstituents. In the past recent decades, however, researchers have made significant progress in developing "new drug delivery systems" (NDDS) to enhance therapeutic efficacy and reduce unwanted effects of bioactive compounds. Nanocapsules, polymer micelles, liposomes, nanogels, phytosomes, nano-emulsions, transferosomes, microspheres, ethosomes, injectable hydrogels, polymeric nanoparticles, dendrimers, and other innovative therapeutic formulations have all been created using bioactive compounds and plant extracts. The novel formulations can improve solubility, therapeutic efficacy, bioavailability, stability, tissue distribution, protection from physical and chemical damage, and prolonged and targeted administration, to name a few. The current study summarizes existing research and the development of new formulations, with a focus on herbal bioactive components.

Optimization and Characterization of Cuscuta reflexa Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability.

The purpose of this study is to determine whether the complexing hydroalcoholic extract of Cuscuta reflexa (HECR) with phosphatidyl choline increases its bioavailability. As a result, a novel phytosomal delivery system for the HECR-soya lecithin complex was developed (HECR-phytosome). The HECR-phytosome complex was synthesized and characterized as phytovesicles. The formulation was prepared using a variable concentration of soya lecithin (1:1-1:3 percent w/v), a temperature range of (45-65°C), and sonication time (4-8 min). Optimization of HECR-loaded phytosomal formulations was performed using Design Expert software. A three-factor, three-level Box-Behnken design was used to optimize this HECR delivery system, as dependent variables, vesicular size and entrapment efficiency were evaluated using a Box Behnken factorial design. Further characterization of the optimized formulation included vesicle size, PDI, zeta potential, entrapment efficiency, FTIR, DSC, TEM, and in vitro release. Vesicle sizes ranged from 173.5±6.17 nm to 215.9±6.53 nm, and response rates for entrapment efficiency ranged from 52.9±1.65 to 77.2±1.1%. The uniform structure and spherical shape were demonstrated by transmission electron microscopy. Among the drug release kinetic models, the formulation followed the Higuchi model (R2 = 0.9978), releasing 96.3±3.7% of the polyphenol and flavonoids phytoconstituents from HECR-loaded phytosomes in 12 hours, compared to 49.3±2.5% in the plain extract. In addition, the optimized formulation passes the stability test. Therefore, the results demonstrated that phytosomal nanocarriers have the potential to increase the bioavailability of Cuscuta reflexa extract.

Trichilia catigua and Turnera diffusa phyto-phospholipid nanostructures: Physicochemical characterization and bioactivity in cellular models of induced neuroinflammation and neurotoxicity.

Flavonoid-based therapies supported by nanotechnology are considered valuable strategies to prevent or delay age-related and chronic neurodegenerative disorders. Egg yolk phospholipids were combined with flavonoid-rich extracts obtained from Trichilia catigua A.Juss. (rich in flavan-3-ols and phenylpropanoid derivatives) or Turnera diffusa Willd. ex Schult (dominated by luteolin derivatives) to prepare nanophytosomes. The nanophytosomes showed that size and surface charge of the lipid-based vesicles are dependent of their phenolic composition. In vitro assays with SH-SY5Y cells showed that both formulations protect cells from glutamate-induced toxicity, but not from 6-hydroxydopamine/ascorbic acid. T. diffusa nanophytosomes promote a decrease of nitric oxide produced by BV-2 cells stimulated with interferon-γ. Nanophytosomes dialysed against a mannitol solution, and then lyophilised, allow to obtain freeze-dried products that after re-hydration preserve the essential physicochemical features of the original formulations, and exhibit improved colloidal stability. These results indicate that these flavonoid/phospholipid-based nanophytosomes have suitable features to be considered as tool in the development of therapeutic and food applications.

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, w/w) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.

Quality by design (Qbd) assisted development of phytosomal gel of aloe vera extract for topical delivery.

The aim of the current study was to develop the phytosomal gel of aloe vera extract for improved topical delivery. Aloe vera extract loaded phytosomal system was developed by fixing the amount of aloe vera extract and ethanol and by varying the concentration of lecithin (0.15-0.25% w/v) and speed of rotation (80-120 rpm). Different formulation batches were prepared as per the Design expert software. A 22 Factorial design was applied to optimize the formulation on the basis of vesicular size and entrapment efficiency. Developed formulations were evaluated for vesicular size, entrapment efficiency, PDI, zeta potential and in-vitro release. Further stability studies were also performed. For the optimized formulation (F09), vesicular size, entrapment efficiency and PDI were found as 123.1 ± 1.44 nm, 95.67 ± 0.27% and 0.98 ± 0.06. Zeta potential of -11.9 mV and drug release of 56.91 ± 4.1% obtained in 24 h. Drug release kinetics from the phytosomes follows Higuchi model. TEM micrograph confirms the uniform structure of phytosomes. Phytosomal gel of optimized phytosomal formulation (F09) was developed with 1% Carbopol 934 and physically characterized on the basis of pH, viscosity, homogeneity and drug content. Ex-vivo permeation study showed the better permeation and flux profile of phytosomal gel with the conventional aloe vera extract gel. Also, studies on phytosomal formulation and gel showed stability up-to 3 months. Thus overall, it can be concluded that the phytosomal gel is a good carrier for topical delivery of herbal extract such as aloe vera.

The Potential Application of Novel Drug Delivery Systems for Phytopharmaceuticals and Natural Extracts - Current Status and Future Perspectives.

Phytocompounds isolated from plants are well appraised for their broad pharmacological propensities in several pathologies. One key benefit of phytoconstituents is their relatively low toxicity and adverse effects. Nonetheless, poor solubility, permeation, and poor specificity at the target site tend to hinder its therapeutic efficacy. Hence, novel technologies for drug delivery systems are being developed via the use of various nanoformulation strategies to overcome these challenges and give uniform medication focusing at the dynamic site in desired concentration and improved therapeutic efficacy. Such approaches comprise of novel drug delivery systems (NDDS). The utilisation of herbal formulations for NDDS is more beneficial and advantageous as opposed to others. The utilisation of ethosome, liposome, emulsion, phytosomes, microsphere, and strong lipid nanoparticles of herbal formulation has improved the remedial impacts of plant extricates. With the utilisation of all these, directed delivery of the formulation is accomplished, because of which the formulation exhibits impact on the site, and its' bioavailability is, likewise, expanded. With these novel medication conveyance frameworks, the actives and concentrates, which are utilised as part of natural formulations, exhibit a sustained release, enhancement in stability, improved therapeutic efficacy, and protection from toxicity. The primary motivation behind creating alternative drug delivery technologies is to expand the effectiveness of drug conveyance and safety in the process and give more comfort to the patient. In this review, the importance of various phytocompounds in the delivery of drugs is highlighted as well as their importance in reducing the risk or diseases.

Selenium-deposited tripterine phytosomes ameliorate the antiarthritic efficacy of the phytomedicine via a synergistic sensitization.

Arthritis remains the notion of a hard-to-treat disease that raises an area of unmet clinical need. The phytomedicine tripterine (Tri) and trace element selenium (Se) have been shown to be of anti-inflammatory activity. This study was devoted to develop nanomedicine containing Tri and Se used for fighting against arthritis via a coordination mechanism. Se-deposited Tri phytosomes (Se@Tri-PTs) were prepared by a melting-hydration/in situ reduction technique and characterized by particle size, ζ potential, morphology, and entrapment efficiency (EE). The resultant Se@Tri-PTs were 126 nm around in particle size with an EE of 98.85%. Se@Tri-PTs exhibited a sustained drug release both in 0.1 M HCl and pH 6.8 PBS compared with Se-free phytosomes (Tri-PTs). The in vivo antiarthritic test demonstrated that Se@Tri-PTs could result in significant resolution of arthritis and decline of inflammatory factors. Phytosomes primely facilitated the transepithelial transport of Tri, while Se enhanced the antiarthritic efficacy of the phytomedicine synergistically. The present work provides a proof-of-concept for the combined therapy of arthritis using Tri and Se in the form of nanoparticles.

Functionalized liposomes and phytosomes loading Annona muricata L. aqueous extract: Potential nanoshuttles for brain-delivery of phenolic compounds.

BACKGROUND: Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2O2) scavenger. PURPOSE: In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced. METHODS: AE and nanoformulations were characterized by HPLC-DAD-ESI-MSn, HPLC-DAD, spectrophotometric, fluorescence and dynamic light scattering methods. Cytotoxicity and permeability studies were carried out using an in vitro transwell model of the BBB, composed of immortalized human microvascular endothelial cells (hCMEC/D3), and in vitro hMAO-A inhibition and H2O2 scavenging activities were performed with all samples. RESULTS: The encapsulation/binding of AE was more efficient with phytosomes, while liposomes were more stable, displaying a slower extract release over time. In general, phytosomes were less toxic than liposomes in hCMEC/D3 cells and, when present, cholesterol improved the permeability across the cell monolayer of all tested nanoformulations. All nanoformulations conserved the antioxidant potential of AE, while phosphatidylcholine interfered with MAO-A inhibition assay. CONCLUSIONS: Overall, phytosome formulations registered the best performance in terms of binding efficiency, enzyme inhibition and scavenging activity, thus representing a promising multipotent phenolic-rich nanoshuttle for future in vivo depression treatment.