Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150 nm) and homogeneous (polydispersity index of 0.162) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models (inhibitory concentrations between 12.37 ng/mL and 14.72 ng/mL). Additionally, they also revealed substantial anti-inflammatory activity (inhibitory concentration of 28.98 ng/mL), effects complementary to direct antitumor activity. Niosome safety was also assessed, both in vitro (skin, liver, and kidney cells) and ex vivo (hen\'s egg chorioallantoic membrane), and results showed that compound encapsulation increased its safety. Hence, small, and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies. Future research should focus on evaluating the potential of the developed platform in in vivo models.

Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug\'s therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.

This study sought to develop a nanoscale delivery system to enhance the stability and bioaccessibility of goat milk whey protein peptides. Goat milk whey protein was hydrolyzed by papain, and the hydrolysate was ultrafiltered to obtain a low molecular weight peptide (GWP, <3 kDa) with strong hypoglycemic activity. The GWP-loaded liposomes and niosomes encapsulation systems were prepared using phytosterols (ergosterol, β-sitosterol, mixed phytosterols, and stigmasterol) instead of cholesterol. Results showed that the GWP-loaded niosomes (GWP-NS) prepared from β-sitosterol had the higher GWP encapsulation efficiency (90.46 ± 4.02 %) and the smaller particle size (92.07 ± 9.8 nm) than liposomes (GWP-LS). Additionally, the morphological results showed that two GWP-loaded systems were smooth and spherical, and the FT-IR spectroscopy confirmed the successful formation of the peptide-loaded system. Compared with GWP, GWP-LS and GWP-NS showed the higher stability under different pH, temperature, and NaCl concentration conditions, especially GWP-NS. Furthermore, GWP-NS could significantly improve the retention rate of GWP during simulated gastrointestinal digestion, in vitro bioaccessibility, and hypoglycemic activity. These findings suggest that β-sitosterol could be a potential membrane stabilizer alternative to cholesterol, and GWP niosomes could be a potential new drug delivery system.

Ginsenosides are the principal bioactive compounds of ginseng. Total ginsenosides (GS) contain a variety of saponin monomers, which have potent anti-photoaging activity and improve the skin barrier function. To enhance the efficiency of GS transdermal absorption, GS liposomes (GSLs) and GS niosomes (GSNs) were formulated as delivery vehicles. Based on the clarified and optimized formulation process, GSL and GSN were prepared. The structure, cumulative transmittance, skin retention, total transmittance, and bioactivity of GSLs and GSNs were characterized. GSL and GSN were shown to inhibit lipid peroxidation and increase the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in human keratinocytes (HaCaTs). In addition, HaCAT cell migration, proliferation, and GS cellular uptake were significantly increased. The therapeutic effects of GSL and GSN were also evaluated in a rat model of photoaging. Histopathological changes were assessed in rat skin treated with GSL, GSN, or GS by hematoxylin-eosin (H&E) and aldehyde fuchsine staining. Malondialdehyde (MDA), SOD, GSH-Px, matrix metalloproteinases (MMPs), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) expression levels were determined. Results indicated that the optimal formulation of GSL used soybean lecithin (SPC) as the phospholipid, with a lipid-drug ratio of 1:0.4 and a phospholipid-cholesterol ratio of 1:3.5. The optimal temperature for the preparation process of GSN by ethanol injection was 65°C, with a ratio of the organic phase to aqueous phase of 1:9. It was demonstrated that the cumulative release rate, skin retention rate, and total transmission rate of GSL-7 at 24 h were higher than those of GSN-4 and GS. GSL-7 significantly inhibited skin lipid peroxidation caused by ultraviolet (UV) radiation. In addition, GSL-7 reduced the contents of MMPs and inflammatory cytokines in skin tissue. In conclusion, GSL-7 may reduce skin aging caused by UV radiation and contribute to skin tissue repair.

Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of -45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes\' activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries.

Human growth hormone (hGH) is widely used to treat several diseases for decades. However, the current treatment regime requires frequent injections via subcutaneous route due to short in vivo half-life, which leads to pain and poor patient compliance. In this study, a novel transdermal (non-invasive) hGH loaded niosomes gel was prepared to reduce the frequency of subcutaneous injections and to improve the patient compliance. Niosomes were prepared by film hydration technique at three levels of cholesterol. The particle size and entrapment efficiency increases with an increase in the level of cholesterol. Transmission electron microscopy images confirmed the spherical shape of niosomes without aggregation. Texture profiles analysis indicates that the niosomal gel has the required mechanical properties for transdermal application. The ex vivo permeation profile showed sustain hGH release for 4 days from the niosomal gel compared to 24 h from the control gel without niosomes. A rabbit skin irritation study showed no sign of irritation after application of niosomal gel. The pharmacokinetic parameters in the rat model showed 7.22-fold higher bioavailability with niosomal gel compared to control gel. In conclusion, the study demonstrated the potential of niosomal gel as an effective long-term sustained release strategy for hGH delivery to replace traditional subcutaneous injections.

Neurocognition is a severe, neurological challenge caused due to sevoflurane application for induction of anaesthesia. The plan of this study is to investigate the effect of fingolimod loaded niosomes on the cognitive impairment induced by sevoflurane. Span 40 and cholesterol were used in reverse phase evaporation techniques for the preparation of fingolimod -loaded niosomes. The positively charged niosomes were obtained by using chloride salts of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The Fingolimod loaded niosomes has average particle size of 223.5 nm and the surface charge measured as + 8.7 ± 1.2 mV in presence of DOTAP. The Fingolimod loaded niosomes formulation shows higher entrapment efficiency. Fingolimod loaded positively charged niosomes were efficiently retained drug and increase the sustain release property. Fingolimod niosomes increases the spontaneous alternation in Y maze and reduces the escape latency in the Morris water maze test, which leads to significant (p < 0.01) improvement in spatial short-term and long-term memory. The neuronal death in the hippocampus due to the sevoflurane exposure was attenuated by fingolimod loaded niosomes, which was proved by histopathological study. It could be defined that fingolimod loaded niosomes attenuates the sevoflurane induced cognitive impairment.

Epigallocatechin gallate (EGCG) has a variety of biological activities, but exhibits poor stability and low bioavailability. In this study, EGCG bilosome was prepared and characterized, and its stability during different storage conditions (pH, NaCl concentration, and temperature) and in gastrointestinal fluid was evaluated and compared with liposomes and niosomes. Among them, EGCG niosomes had the highest pH stability, and the existence of sodium cholate reduced the stability of bilosomes in acidic medium. EGCG stability was significantly increased in the presence of salt ions (0-100 mM NaCl) and under different temperatures (25 °C, 37 °C) when delivered as niosomes and bilosomes. Retention rate of EGCG in bilosomes was 71.64 ± 4.05% after incubation in simulated intestinal fluid for 2 h, which was significantly higher than retention rate of EGCG liposomes (24.02 ± 3.95%) and niosomes (55.74 ± 6.85%), thus indicating greater gastrointestinal stability of EGCG bilosomes. Furthermore, bioavailability of EGCG encapsulated in bilosomes was improved by 1.98 times. Overall, these findings indicate that EGCG bilosomes, as a new delivery system, had great potential application as a means to improve stability and bioavailability of EGCG.

Increasing the drug tumor-specific accumulation and controlling their release is considered one of the most effective ways to increase the efficacy of drugs. Here, we developed a vesicle system that can target hepatoma and release drugs rapidly within tumor cells. This non-ionic surfactant vesicle is biodegradable. Galactosylated stearate has been used to glycosylate the vesicles to achieve liver targeting; replacement of a portion (Chol:CHEMS = 1:1) of cholesterol by cholesteryl hemisuccinate (CHEMS) allows for a rapid release of drugs in an acidic environment. In vitro release experiments confirmed that galactose-modified pH-sensitive niosomes loaded with tanshinone IIA had excellent drug release performance in acid medium. In vitro experiments using ovarian cancer cells (A2780), colon cancer cells (HCT8), and hepatoma cell (Huh7, HepG2) confirmed that the preparation had specific targeting ability to hepatoma cells compared with free drugs, and this ability was dependent on the galactose content. Furthermore, the preparation also had a more substantial inhibitory effect on tumor cells, and subsequent apoptosis assays and cell cycle analyses further confirmed its enhanced anti-tumor effect. Results of pharmacokinetic experiments confirmed that the vesicle system could significantly extend the blood circulation time of tanshinone IIA, and the larger area under the curve indicated that the preparation had a better drug effect. Thus, the results of biodistribution experiments confirmed the in vivo liver targeting ability of this preparation. Niosomes designed in this manner are expected to be a safe and effective drug delivery system for liver cancer therapy.

Propofol is an oily liquid widely used for rapid onset of anaesthesia via intravenous route, which shows major limitations of hypersensitivity, anaphylactic reactions and pain. The aim of the present work was to bypass the above issues by formulating tailored niosomal gel to deliver propofol via non-invasive transdermal route. The niosomes were prepared by film hydration method and sonication using cholesterol and Span 80. The Box Behnken design (BBD) was applied to optimize the size (93.5 nm) and the entrapment efficacy (81.5%) of the niosomes by selecting cholesterol at 139 mg, Span 80 at 0.525% and sonication time at 5.13 min. The scanning electron microscopy image showed spherical shape niosomes with smooth surface without aggregation. The ex vivo release data showed significant improvement in the propofol release (92.2% after 10 h) using niosomes in comparison to the control propofol gel (with 30% methanol) without niosomes (25.3% after 10 h). The in vivo pharmacokinetic parameters in the rat model confirmed the improvement in the relative bioavailability with optimized niosomal gel (relative bioavailability = 12.12) in comparison to the control propofol gel. In conclusion, the niosomal gel offered a potential alternative non-invasive route to deliver propofol for procedural sedation especially in pediatric population.