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Caffeine (CAF) is a challenging natural bioactive compound with proven antiaging efficacy. However, being hydrophilic hampers its permeation through the skin. Our aim is to develop a novel CAF-loaded nano-cosmeceutical tool counteracting skin photoaging via improving CAF skin permeation using a bioactive nanocarrier. Caffeinated hyalurosomes are novel biocompatible antiaging nanoplatforms designed by immobilization of phospholipid vesicles with a hyaluronan polymer. Physicochemical properties of the selected hyalurosomes formulation showed nano-sized vesicles (210.10 ± 1.87 nm), with high zeta potential (−31.30 ± 1.19 mv), and high encapsulation efficiency (84.60 ± 1.05%). In vitro release results showed outstanding sustained release profile from caffeinated hyalurosomes compared to the CAF-loaded in conventional gel over 24 h. The in-vivo study revealed a photoprotective effect of caffeinated hyalurosomes, reflected from the intact and wrinkling-free skin. Results of biochemical analyses of oxidative stress, pro-inflammatory mediators, and anti-wrinkling markers further confirmed the efficacy of the prepared hyalurosomes compared to the CAF conventional gel. Finally, histopathological examination demonstrated normal histological structures of epidermal layers with minimal inflammatory cell infiltrates in the caffeinated hyalurosomes group compared to the positive control group. Conclusively, caffeinated hyalurosomes successfully achieved enhanced CAF loading and penetration into the skin besides the hydration effect of hyaluronan. Consequently, the developed delivery system presents a promising skin protection nano-platforms via the double effects of both hyaluronan and CAF, hence it guards against skin photodamage.

Curcumin (CU) is a natural polyphenolic phytoingredient. CU has anti-inflammatory, anti-oxidant, and anticancer activities. The poor solubility, bioavailability, and stability of CU diminish its clinical application. Hence, structural modification of CU is highly recommended. The CU analog; 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (PIP) exhibited high stability, safety, and more potent antiproliferative activity against hepatocellular carcinoma. In the present study, nano-bilosomes (BLs) were formulated to augment PIP delivery and enhance its solubility. A 21.31 full factorial design was adopted to prepare the synthesized PIP-loaded BLs. Optimized F4 showed a biphasic release pattern extended over 24 h, with EE%, ZP, and PS of 90.21 ± 1.0%, −27.05 ± 1.08 mV, and 111.68 ± 1.4 nm. PIP-loaded BLs were tested for safety against a non-cancerous cell line (Wi-38) and for anticancer activity against the Huh-7 human hepatocellular carcinoma cells and compared to the standard anticancer drug doxorubicin (Dox). The anticancer selectivity index of PIP-loaded BLs recorded 420.55 against Huh-7 liver cancer cells, markedly higher than a CU suspension (18.959) or the Dox (20.82). The antiproliferative activity of nano-encapsulated PIP was roughly equivalent to Dox. PIP-loaded BLs, showed enhanced drug solubility, and enhanced anticancer effect, with lower toxicity and higher selectivity against Huh-7 liver cancer cells, compared to the parent CU.

Despite the fact of availability of several treatments for breast cancer, most of them fail to attain the desired therapeutic response due to their poor bioavailability, high doses, non-selectivity and as a result systemic toxicity. Here in an attempt made to study the transdermal effect of leflunomide (LEF) against breast cancer. In order to improve the poor physicochemical properties of LEF, it was loaded into cubosomes. Cubosomes were prepared by the emulsification method. Colloidal characteristics of cubosomes including particle size, ζ-potential, entrapment efficiency, in-vitro release profile and ex-vivo permeation were studied. In addition, morphology, stability, cytotoxicity and cell uptake in MDA-MB-231 cell line were carried out for the selected cubosomal formulation. The selected LEF loaded cubosomal formulation showed a small particle size (168 ± 1.08) with narrow size distribution (PI 0.186 ± 0.125) and negative ζ potential (–25.5 ± 0.98). Its Entrapment efficiency (EE%) was 93.2% and showed sustained release profile that extended for 24 h. The selected formulation showed stability when stored at 25 °C for three months in terms of size and EE%. TEM images illustrated the cubic structure of the cubosome. Cell culture results revealed the superiority of LEF cubosomes compared to LEF suspension in their cytotoxic effects with an IC50 close to that of doxorubicin. Furthermore, LEF cell uptake was significantly higher for LEF cubosomes. This may be attributed to the effect of nano-encapsulation on enhancing drug pharmacological effects and uptake indicating the potential usefulness of LEF cubosomes for breast cancer management.

Abstract A shift towards natural anti-aging ingredients has spurred the research to valorize traditionally used plants. In this context, Rosmarinus officinalis L. was evaluated for its photoprotective, antioxidant, anti-inflammatory, and anti-wrinkling properties. GC/MS and LC-ESI-HRMS based phytochemical profiling of rosemary leaves hexane extract resulted in the identification of 47 and 31 compounds, respectively and revealed rich content in triterpenoids, monoterpenoids and phenolic diterpenes. In vitro assays confirmed the antioxidant, anti-aging, and wound healing potential of rosemary extract along with a good safety profile, encouraging further development. A systematic molecular modelling study was conducted to elucidate the mechanistic background of rosemary anti-aging properties through the inhibitory effects of its major constituents against key anti-aging targets viz. elastase, collagenase, and hyaluronidase. Development of rosemary extract lipid nanocapsules-based mucoadhesive gels was performed to improve skin contact, permeation, and bioavailability prior to in vivo testing. The developed formulae demonstrated small particle size (56.55–66.13 nm), homogenous distribution (PDI of 0.207–0.249), and negatively charged Zeta potential (− 13.4 to − 15.6). In UVB-irradiated rat model, topical rosemary hexane extract-loaded lipid nanocapsules-based gel provided photoprotection, restored the antioxidant biochemical state, improved epidermal and dermal histological features, and decreased the level of inflammatory and wrinkling markers. The use of rosemary hexane extract in anti-aging and photoprotective cosmeceuticals represents a safe, efficient, and cost-effective approach.

The recent interest in bioactive compounds from natural sources has led to the evolution of the skin care industry. Efforts to develop biologically active ingredients from natural sources have resulted in the emergence of enhanced skin care products. Spirulina (SPR), a nutritionally enriched cyanobacteria-type microalga, is rich in nutrients and phytochemicals. SPR possesses antioxidant, immunomodulatory, and anti-inflammatory activities. Spirulina-loaded bilosomes (SPR-BS), a novel antiaging drug delivery system, were designed for the first time by incorporation in a lecithin–bile salt-integrated system for bypassing skin delivery obstacles. The optimized BS had good entrapment efficiency, small particle size, optimal zeta potential, and sustained drug release pattern. Blank and SPR-loaded BS formulations were safe, with a primary irritancy index of

The vast socio-economic impact of Alzheimer’s disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O-glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, β-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.

Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.

Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer’s disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer’s disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators’ levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.

Impaired memory and cognitive function are the main features of Alzheimer’s disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.

Alzheimer’s disease (AD) is a neurodegenerative disease where oxidative stress plays a major role as a key pathologic factor. The study aims to develop resveratrol (RES)-loaded bilosomes for oral use, aiming to enhance RES bioavailability. RES-loaded bilosomes were prepared using the thin-film hydration technique. The effect of different formulation variables viz. the number of extrusion cycles, drug concentration and the effect of pH of the medium and cholesterol addition on the physicochemical properties of the prepared bilosomes was investigated. Results revealed the successful entrapment of RES into bilosomes. An optimized formula was selected, showing the lowest particle size (189 ± 2.14), acceptable PDI (0.116) and entrapment efficiency (76.2 ± 1.36). In vivo studies on a streptozotocin-induced animal model of AD showed the preeminence of bilosomes over traditional drug suspension to enhance mice memory via Y-maze and Morris water maze tests. Moreover, mice treated with the optimized formula exhibited decreased COX2, IL-6, amyloid-beta peptide and Tau protein levels compared to the drug suspension. Immuno-histochemical analysis revealed a significant decrease of glial fibrillary acidic protein values and microglial cell count in mice treated with bilosomes. Finally, it could be advocated that RES-loaded bilosomes could be a promising drug delivery system to control AD.