Liposomes, transfersomes and niosomes: production methods and their applications in the vaccinal field.

One of the most effective strategies to fight viruses and handle health diseases is vaccination. Recent studies and current applications are moving on antigen, DNA and RNA-based vaccines to overcome the limitations related to the conventional vaccination strategies, such as low safety, necessity of multiple injection, and side effects. However, due to the instability of pristine antigen, RNA and DNA molecules, the use of nanocarriers is required. Among the different nanocarriers proposed for vaccinal applications, three types of nanovesicles were selected and analysed in this review: liposomes, transfersomes and niosomes. PubMed, Scopus and Google Scholar databases were used for searching recent papers on the most frequently used conventional and innovative methods of production of these nanovesicles. Weaknesses and limitations of conventional methods (i.e., multiple post-processing, solvent residue, batch-mode processes) can be overcome using innovative methods, in particular, the ones assisted by supercritical carbon dioxide. SuperSomes process emerged as a promising production technique of solvent-free nanovesicles, since it can be easily scaled-up, works in continuous-mode, and does not require further post-processing steps to obtain the desired products. As a result of the literature analysis, supercritical carbon dioxide assisted methods attracted a lot of interest for nanovesicles production in the vaccinal field. However, despite their numerous advantages, supercritical processes require further studies for the production of liposomes, transfersomes and niosomes with the aim of reaching well-defined technologies suitable for industrial applications and mass production of vaccines.

Duo photoprotective effect via silica-coated zinc oxide nanoparticles and Vitamin C nanovesicles composites.

OBJECTIVE: Zinc Oxide nanoparticles (ZnO NPs) are used widely in nowadays personal care products, especially sunscreens, as a protector against UV irradiation. Yet, they have some reports of potential toxicity. Silica is widely used to cage ZnO NPs to reduce their potential toxicity. Vitamin C derivative, Magnesium Ascorpyl Phosphate (MAP), is a potent antioxidant that can efficiently protect human skin from harmful impacts of UV irradiation and oxidative stress. The combination of silica coated ZnO NPs and MAP nanovesicles could have potential synergistic protective effect against skin photodamage. METHODS: Silica coated ZnO NPs and MAP nanovesicles (ethosomes and niosomes) were synthesized, formulated, and evaluated as topical gels. These gel formulations were evaluated in mice for their photoprotective effect against UV irradiation through histopathology and immuno-histochemistry study. Split-face clinical study was conducted to compare the effect of application of silica coated ZnO NPs either alone or combined with MAP nanovesicles. Their photoprotective action was evaluated, using Antera 3D® camera, for melanin level, roughness index and wrinkles depth. RESULTS: Silica coated ZnO NPs when combined with MAP nanovesicles protected mice skin from UV irradiation and decreased the expression of the proinflammatory cytokines, NF-κB. Clinically, silica coated ZnO NPs, alone or combined with MAP nanovesicles, could have significant effect to decrease melanin level, roughness index and wrinkles depth with higher effect for the combination. CONCLUSION: A composite of silica coated ZnO NPs and MAP nanovesicles could be a promising cosmetic formulation for skin protection against photodamage signs such as hyperpigmentation, roughness, and wrinkles.

Machine learning algorithms for prediction of entrapment efficiency in nanomaterials.

Exploitation of machine learning in predicting performance of nanomaterials is a rapidly growing dynamic area of research. For instance, incorporation of therapeutic cargoes into nanovesicles (i.e., entrapment efficiency) is one of the critical parameters that ensures proper entrapment of drugs in the developed nanosystems. Several factors affect the entrapment efficiency of drugs and thus multiple assessments are required to ensure drug retention, and to reduce cost and time. Supervised machine learning can allow for the construction of algorithms that can mine data available from earlier studies to predict performance of specific types of nanoparticles. Comparative studies that utilize multiple regression algorithms to predict entrapment efficiency in nanomaterials are scarce. Herein, we report on a detailed methodology for prediction of entrapment efficiency in nanomaterials (e.g., niosomes) using different regression algorithms (i.e., CatBoost, linear regression, support vector regression and artificial neural network) to select the model that demonstrates the best performance for estimation of entrapment efficiency. The study concluded that CatBoost algorithm demonstrated the best performance with maximum R2 score (0.98) and mean square error (< 10-4). Among the various parameters that possess a role in entrapment efficiency of drugs into niosomes, the results obtained from CatBoost model revealed that the drug:lipid ratio is the major contributing factor affecting entrapment efficiency, followed by the lipid:surfactant molar ratio. Hence, supervised machine learning may be applied for future selection of the components of niosomes that achieve high entrapment efficiency of drugs while minimizing experimental procedures and cost.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Olive oil and flaxseed oil incorporating niosomes for enhanced in vivo anti-diabetic efficacy of canagliflozin.

BACKGROUND: Canagliflozin (CFZ) is broadly implicated for the management of type 2 diabetes mellitus. Unfortunately, it has low oral bioavailability due to poor solubility behavior and restricted membrane permeability. OBJECTIVE: The current work focuses on development of CFZ encapsulated niosomes for enhanced oral anti-diabetic efficacy. METHODOLOGY: Niosomes comprising Span 60 and cholesterol were formulated both in absence and presence of olive oil or flaxseed oil. These were evaluated in vitro for average vesicular size, structural morphology, CFZ entrapment efficiency, and drug release. Additionally, the oral hypoglycemic effect of CFZ encapsulated niosomes was explored in diabetic rats. RESULTS: The fabricated niosomes were negatively charged spherical vesicles with a size range of 103.0-141.7 nm. These entrapped CFZ with efficiency ranging from 92.3% to 96.0%. Drug release investigations reflected that incorporating CFZ into niosomes significantly sustained drug release compared to the aqueous drug dispersion. Oral administration of niosomal formulations significantly enhanced the oral antidiabetic effect of CFZ. Comparing the tested niosomes, similar efficiency was shown eliminating the effect of composition. CONCLUSION: The enhanced oral bioavailability of niosomes' encapsulated drugs is related to niosomal vesicular structure which allows intact niosomes absorption. The study presented niosomes as promising carriers for improved oral anti-diabetic activity of CFZ.

Radioprotective effect of nanoniosome loaded by Mentha Pulegium essential oil on human peripheral blood mononuclear cells exposed to ionizing radiation.

OBJECTIVE: The present study aimed to assess the radioprotective effect of nanoniosomes loaded by Mentha Pulegium essential oil (MPEO-N nanoparticles) as a natural antioxidant on human peripheral blood mononuclear cells (PBMCs). SIGNIFICANCE: Despite the applications and advantages of ionizing radiation, there are many radiation risks to biological systems that are necessary to be reduced as much as possible. METHODS: MPEO-N nanoparticles were prepared by the lipid thin film hydration method, and its physicochemical characteristics were analyzed. PBMCs were then irradiated with X-ray using a 6 MV linear accelerator at two radiation doses in the presence of nontoxic concentrations of MPEO-N nanoparticles (IC10). After 48 and 72 h of incubation, the radioprotective effect was investigated by measuring survival, apoptosis, and necrosis of PBMCs, using MTT assay and flow cytometry analysis. KEY FINDINGS: The hydrodynamic diameter and zeta potential of nanoniosomes were 106.0 ± 4.69 nm and -15.2 ± 0.9 mV, respectively. The mean survival percentage of PBMCs showed a significant increase only at a radiation dose of 200 cGy compared with the control group. The percentages of apoptosis and necrosis of cells in the presence of MPEO-N nanoparticles at both radiation doses and incubation periods (48 and 72 h) demonstrated a significant reduction compared with the control. CONCLUSION: MPEO-N nanoparticles as a natural antioxidant, exhibited a favorable radioprotective effect by a significant reduction in the percentage of apoptosis and necrosis of irradiated PBMCs.

Liposomes like advanced drug carriers: from fundamentals to pharmaceutical applications.

AIMS: There are around 24 distinct lipid vesicles described in the literature that are similar to vesicular systems such as liposomes. Liposome-like structures are formed by combining certain amphiphilic lipids with a suitable stabiliser. Since their discovery and classification, self-assembled liposome-like structures as active drug delivery vehicles captured researchers' curiosity. METHODOLOGY: This comprehensive study included an in-depth literature search using electronic databases such as PubMed, ScienceDirect and Google Scholar, focusing on studies on liposome and liposomes like structure, discussed in literature till 2024, their sizes, benefits, drawback, method of preparation, characterisation and pharmaceutical applications. RESULTS: Pharmacosomes, cubosomes, ethosomes, transethosomes, and genosomes, all liposome-like structures, have the most potential due to their smaller size with high loading capacity, ease of absorption, and ability to treat inflammatory illnesses. Genosomes are futuristic because of its affinity for DNA/gene transport, which is an area of focus in today's treatments. CONCLUSION: This review will critically analyse the composition, preparation procedures, drug encapsulating technologies, drug loading, release mechanism, and related applications of all liposome-like structures, highlighting their potential benefits with enhanced efficacy over each other and over traditional carriers by paving the way for exploring novel drug delivery systems in the Pharma industry.

Optimization and Synthesis of Nano-Niosomes for Encapsulation of Triacontanol by Box-Behnken Design.

Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box-Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (-31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400-300 cm-1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.

Vesicular Carriers for Improved Oral Anticoagulation Competence of Rivaroxaban: In Vitro and In Vivo Investigation.

Rivaroxaban is an anticoagulant for avoidance and therapy of thromboembolic disorders. Unfortunately, oral bioavailability of rivaroxaban is compromised with dose increments. Accordingly, the aim was to test nano-vesicular lipid systems for improved oral anticoagulation activity of rivaroxaban. Rivaroxaban loaded niosomes, bilosomes and spanlastic formulations were prepared. The prepared systems were assessed in terms of particle size, zeta potential, transition electron microscopic features (TEM), entrapment efficiency, in-vitro drug release, and in-vivo anticoagulation performance in rats. The prepared vesicular systems exposed spherical negatively charged vesicles with mean particle size values between 136.6 nm to 387.9 nm depending on the composition. Rivaroxaban was efficiently entrapped in the vesicular systems with entrapment efficiency values ranging from 92.4% to 94.0%. Rivaroxaban underwent sustained release from the fabricated vesicular systems. The in vivo performance of the tested preparation revealed significant enhancement of the anticoagulation parameters. This was manifested from the prolonged clotting time, and prothrombin time. Moreover, the cut tails of the examined rats receiving the formulated nano-systems exposed a lengthy tail bleeding time compared to those receiving the un-processed rivaroxaban aqueous dispersion. In Conclusion, niosomes, bilosomes and spanlastic nano-dispersions have a potential to overwhelm the oral anticoagulation efficiency of rivaroxaban with spanlastic ranked as best.

Efficient Delivery of Gold Nanoparticles and miRNA-33a Via Cationic PEGylated Niosomal Formulation to MCF-7 Breast Cancer Cells.

To overcome the challenges associated with the co-delivery of AuNPs (gold nanoparticles) and miRNA as an anti-breast cancer combination therapy, niosomal systems were developed using Span 60, cholesterol, and a cationic lipid (CTAB), and the formulations were optimized using Box-Behnken experimental design. The niosomal formulations with the smallest size were selected for further optimization of size, surface charge, entrapment efficiency, and stability. To achieve this, AuNPs and DSPE-PEG2000 (2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000)were added to the formulation. The optimized niosomal formulation could effectively encapsulate AuNPs with an entrapment efficiency of 34.49% ± 0.84 and a spherical particle size of 153.6 ± 4.62 nm. The incorporation of PEG and CTAB led to notable enhancements in the overall characteristics of the delivery system. To evaluate the effectiveness of the combination therapy, various assessments such as cytotoxicity, apoptosis, and gene expression properties were conducted. The results demonstrated that the combination delivery using the new C-PEG-Nio-AuNPs (cationic pegylated niosomal gold nanoparticles) system and miRNA had the lowest IC50, the highest apoptosis rate, and the most significant upregulation of miRNA and BAX/BCL2 expression in MCF-7 cell growth. In conclusion, this innovative co-delivery approach represents a promising breakthrough in the development of therapeutic agents for breast cancer treatment. By combining multiple therapeutic agents within a single delivery system, this method has the potential to enhance treatment efficacy, reduce side effects, and improve patient outcomes.

Thermosensitive and mucoadhesive gels containing solid lipid nanoparticles loaded with fluconazole and niosomes loaded with clindamycin for the treatment of periodontal diseases: a laboratory experiment.

BACKGROUND: Periodontal diseases may benefit more from topical treatments with nanoparticles rather than systemic treatments due to advantages such as higher stability and controlled release profile. This study investigated the preparation and characterization of thermosensitive gel formulations containing clindamycin-loaded niosomes and solid lipid nanoparticles (SLNs) loaded with fluconazole (FLZ), as well as their in vitro antibacterial and antifungal effects in the treatment of common microorganisms that cause periodontal diseases. METHODS: This study loaded niosomes and SLNs with clindamycin and FLZ, respectively, and assessed their loading efficiency, particle size, and zeta potential. The particles were characterized using a variety of methods such as differential scanning calorimetry (DSC), dynamic light scattering (DLS), and Transmission Electron Microscopy (TEM). Thermosensitive gels were formulated by combining these particles and their viscosity, gelation temperature, in-vitro release profile, as well as antibacterial and antifungal effects were evaluated. RESULTS: Both types of these nanoparticles were found to be spherical (TEM) with a mean particle size of 243.03 nm in niosomes and 171.97 nm in SLNs (DLS), and respective zeta potentials of -23.3 and -15. The loading rate was 98% in niosomes and 51% in SLNs. The release profiles of niosomal formulations were slower than those of the SLNs. Both formulations allowed the release of the drug by first-order kinetic. Additionally, the gel formulation presented a slower release of both drugs compared to niosomes and SLNs suspensions. CONCLUSION: Thermosensitive gels containing clindamycin-loaded niosomes and/or FLZ-SLNs were found to effectively fight the periodontitis-causing bacteria and fungi.

Nanocrocin Protective Effects on Paraquat-Induced Oxidative Stress in the MRC-5 Cell Line.

Paraquat (PQ) herbicide poisoning is a severe medical problem in developing countries without suitable therapy. This study aimed to investigate the effects of crocin (CCN) and nano crocin (NCCN) on PQ -induced toxicity in the MRC-5 cell line. The results showed that the particle size of NCCN was 140.3 ± 18.0 nm, and the zeta potential of the optimal crocin-loaded niosomes was 23.4 ± 2.8 mV. The NCCN was more effective than CCN in the inhibition of PQ-induced toxicity. Treatment of the MRC-5 cells leads to a decrease in ROS and an increase in SOD, CAT, GPX, and TAC levels in PQ-CCN and PQ-NCCN groups compared with the PQ group. These changes tended to be positively associated with the NCCN compared to CCN. Overall, NCCN was more effective than crocin in treating PQ-induced toxicity in vitro and deserved further preclinical consideration.

Niosomes based formulation containing tenoxicam: A newer solution for the rheumatic diseases.

OBJECTIVE: This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of rheumatic diseases. MATERIAL AND METHODS: Mechanical dispersion technique with controlled pressure was employed to prepare different niosomal formulations. The effects of different ratios of surfactant (span-60), lipid, and sodium deoxycholate on noisome's physicochemical properties have been examined. Moreover, inhibition of TNF-α in lipopolysaccharide-activated cultured Human leukemia monocytic (THP-1) cells were demonstrated to assess the in vitro inflammation profile. Finally, the optimized niosomal formulation (TN3) was prepared in gel matrix consist of carbopol 934 (termed as TN34) and stability was also tested at 4±2 ÌŠC, 25±2 ÌŠC, 37±2 ÌŠC and 45±2 ÌŠC for 6 months. RESULTS: The optimized niosomal formulation exhibited a small vesicle size (165±14nm) and high drug encapsulation (79.64±1.5%). Niosomal gel formulation TN34 showed pH (6.7), viscosity (6810±3.34 cps), spreadability (19.11±1.87gm.cm/sec) and also displayed sustained release pattern of drug release (98.16±0.07% TN released from gel matrix in 24h) in vitro release study. TN34 exhibited substantial anti-inflammatory response, with ∼75% inhibition of TNF-α in 48h. Stability investigation revealed that refrigerator temperature is most suitable for the storage of niosomal gel. CONCLUSION: Transdermal niosomal formulation displayed promising potential in the treatment of rheumatic diseases.

Potential cardioprotective and anticancer effects of carvedilol either free or as loaded nanoparticles with or without doxorubicin in solid Ehrlich carcinoma-bearing mice.

AIM: The aim of this study was to investigate the potential cardioprotective and anti-cancer effects of carvedilol (CAR) either free or as loaded nano-formulated with or without doxorubicin (DOX) in solid Ehrlich carcinoma (SEC)-bearing mice. It focused on assessment of cardiac damage, drug resistance, apoptosis, oxidative stress status, angiogenesis and proliferation. METHODS: CAR was loaded into poly-D,L lactic-co-glycolic acid)PLGA(or Niosomes. SEC was induced in female albino mice as an experimental model of breast cancer. Seventy-two mice were randomly divided into 9 equal groups (Normal control, Untreated-SEC, SEC + DOX, SEC + CAR-free, SEC + CAR-PLGA, SEC + CAR-Niosomes, SEC + DOX + CAR-free, SEC + DOX + CAR-PLGA and SEC + DOX + CAR-Niosomes). Tumor volume and survival rate were recorded. On day 28 from tumor inoculation, mice were sacrificed, and blood samples were collected for determination of serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). One part from tumor tissues was prepared for assessment of multidrug resistance protein-1 (MDR-1), caspase-3, reduced glutathione (GSH) and malondialdehyde (MDA), while the other part was processed for histopathological examination and immunohistochemical expression of vascular endothelial growth factor (VEGF) and Ki-67. RESULTS: There was non-significant difference between CAR-free, CAR-PLGA and CAR-Niosomes as anticancer either alone or when combined with DOX. However, CAR-free demonstrated potential cardioprotective effects against cardiac damage mediated by cancer or DOX that have been enhanced using CAR-PLGA or CAR-Niosomes, but that of Niosomes outperformed them both. CONCLUSION: CAR could be used as an adjuvant therapy with DOX, especially when nanoformualted with PLGA and even better with Niosomes, without compromising its cytotoxicity against cancer cells and preventing its cardiotoxic impacts.

Methods for preparation of niosomes: A focus on thin-film hydration method.

Development of nanocarriers has opened new avenues for the delivery of therapeutics of various pharmacological activities with improved targeting properties and reduced side effects. Niosomes, non-ionic-based vesicles, have drawn much interest in various biomedical applications, owing to their unique characteristics and their ability to encapsulate both hydrophilic and lipophilic cargoes. Niosomes share structural similarity with liposomes while overcoming limitations associated with stability, sterilization, and large-scale production of liposomes. Different methods for preparation of niosomes have been described in the literature, each having its own merits and a great impact on the sizes and characteristics of the formed niosomes. In this article, procedures involved in the thin-film hydration method, a commonly used method for the preparation of niosomes, are described in detail, while highlighting precautions that should be considered for consistent and reproducible construction of niosomes.

A green-based approach for noninvasive skin rejuvenation: Potential application of hyaluronic acid.

Gradually, loss of skin elasticity and elastic properties occurs after 30 years of age and will be associated with several changes, including creating wrinkles, skin laxity (sagging skin), and skin blemishes. In general, people all over the world are looking for ways to keep their facial skin young over time. There are several strategies to skin rejuvenate, including invasive and non-invasive methods. However, invasive methods have less popularity than non-invasive methods due to their need for specialist physicians (medical expertise), localized neuropathic pains for patients, the prevalence and incidence of skin infections, and high-cost clinical services. In the meantime, skin hydration is one of the simplest non-invasive methods for skin rejuvenation, and HA, with anti-aging and skin collagen-stimulating properties, has been introduced as a natural skin moisturizing agent. Therefore, since this composition maintains facial skin moisture and radiance, and improves its elasticity, it has always been considered by experts and specialist physicians. On the other hand, due to its lipophilic properties, hydrophilic macromolecules containing HA cannot pass through the stratum corneum. However, they have temporary and superficial softening effects on the skin. Hence, some nanocarriers have been suggested to overcome this problem and develop the properties and positive influences of HA on skin rejuvenation. Therefore, the present study aimed to introduce some new non-invasive approaches in facial skin rejuvenation, including applying liposomes, niosomes, ethosomes, and ionic liquids, to transport HA into the inner and deeper layers of the skin, including Dermis. In this review article, we examine non-invasive methods using nanoparticles to deliver HA to the epidermis and dermis of the skin for skin rejuvenation.

Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

Recent updates in curcumin delivery.

Curcumin is a natural component extracted from the rhizomes of turmeric (Curcuma longa), a natural plat with known medicinal uses for more than 4000 years. Most turmeric therapeutic effects are attributed to curcumin, a yellow-coloured extract. Curcumin has received considerable attention due to its biological activities, such as its use in arthritis, liver and neurodegenerative diseases, obesity, and several types of cancers. Most of these curcumin therapeutic activities are related to its antioxidant and anti-inflammatory effects. However, the clinical application of curcumin is hampered by some limitations that prevent its extensive clinical application. Curcumin high hydrophobicity of curcumin and limited water solubility are among the most important limitations. This poor solubility will result in low bioavailability due to its poor absorption into plasma and the target tissues. Curcumin also has rapid metabolism, which will significantly lower its bioavailability and shorten its half-life. Moreover, curcumin is photosensitive with limited chemical stability during manufacturing and storage. These limitations have been overcome by applying nanotechnology using several types of nanoparticles (NPs). This includes using NPs such as liposomes, niosomes, gold nanoparticles, and many others to improve the curcumin solubility and bioavailability. This review focuses on the different types of NPs investigated and the outcomes generated by their use in the most recent studies in this field. To follow the latest advances in the field of site-specific drug delivery using nanomaterials, an electronic databases search was conducted using PubMed, Google scholar and Scopus using the following keywords: lipid-based nanoparticles, curcumin delivery, niosomes, and liposomes.

Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer.

Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes' cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL). In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.