Hen's Egg Chorioallantoic Membrane Research Articles

Bee Venom-Loaded Niosomes as Innovative Platforms for Cancer Treatment: Development and Therapeutical Efficacy and Safety Evaluation.

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.

Enhancement of Biological Activities and Phytochemical Compounds of Oryza sativa L. Extract through Probiotic Fermentation

This study aimed to enhance the biological effects and phytochemical content of probiotic fermented red jasmine rice (Oryza sativa L.) extract to apply as a functional ingredient in anti-aging application. In addition, safety evaluation in terms of cytotoxicity and irritation profile were explored. Lactobacillus plantarum and Lactobacillus rhamnosus were used to ferment the aqueous extract of red jasmine rice to produce fermented extracts as BG and LRB, respectively. The biological potentials in terms of antioxidation, anti-enzymatic effects and anti-inflammation with cytotoxicity of fermented extracts were evaluated and compared with nonfermented extract. In addition, alteration in phytochemical constituents of the probiotic-fermented extracts from nonfermented extract were illustrated by synchrotron radiation–based–FTIR microspectroscopy (SR-FT-IR). The results revealed that BG and LRB demonstrated improved antioxidant and anti-tyrosinase effects compared to the control. Additionally, BG and LRB significantly increased the total phenolic contents corresponding to the enhanced biofunctional effects confirmed by SR-FT-IR. Moreover, BG showed a satisfactory safety in human skin cell lines and Hen's egg chorioallantoic membrane. This study implied augmentative effect of probiotic fermentation on the bioactive efficacy of red jasmine rice. Additionally, the safety investigation confirmed that this fermented extract could be used as a functional novel ingredient for anti-aging nutraceutical and cosmetic applications.

Endophthalmitis therapy revolution: Proof of concept based on in vivo evaluation of maleic acid modified chitosan

The aim was to develop chitosan-maleic acid (CS-MA) based ocular inserts with enhanced mucoadhesiveness for prevention of endophthalmitis caused by Escherichia coli. Therefore, chitosan (CS) and maleic acid (MA) were conjugated via formation of amide bond. Characterization via proton nuclear magnetic resonance and infrared spectroscopy was carried out and attached maleic acid groups were quantified by free amino groups assay. Biocompatibility of the conjugate was assessed following resazurin assay on fibroblasts, membrane damage on human erythrocytes and Hen's Egg-Chorioallantoic membrane tests. Inserts were pressed and characterized in terms of swelling behavior, pH, hardness, in vitro drug release and disintegration. To test mucoadhesive properties of CS-MA inserts, rheometer, rotating cylinder, inclined plane, and texture analyzer were the instruments utilized. Furthermore, antibacterial efficacy of the conjugate was established by direct agar diffusion method and in vivo Draize test was carried out to determine tolerability of the inserts. Results exhibited successful synthesis of the biomaterial, maintaining the great biocompatibility of native chitosan even though a 68.81 % of modification was achieved. Additionally, mucoadhesive studies showed improved properties of CS-MA compared to native polymer, with 2.42-fold, 4-fold, 3.42-fold and 4.05-fold increase in dynamic viscosity, retention time, overall attachment work and peak force of detachment, respectively. Finally, antibacterial activity was enhanced in 1.77-fold and in vivo experiments showed no irritation and good tolerability of CS-MA inserts. In conclusion, CS-MA ocular inserts effectively developed exhibiting promising features capable of revolutionizing the endophthalmitis therapy field.

Acer tegmentosum extract-mediated silver nanoparticles loaded chitosan/alginic acid scaffolds enhance healing of E. coli-infected wounds

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.

Glycol Chitosan-Poly(lactic acid) Conjugate Nanoparticles Encapsulating Ciprofloxacin: A Mucoadhesive, Antiquorum-Sensing, and Biofilm-Disrupting Treatment Modality for Bacterial Keratitis.

Bacterial keratitis (BK) causes visual morbidity/blindness if not treated effectively. Here, ciprofloxacin (CIP)-loaded nanoparticles (NPs) using glycol chitosan (GC) and poly(lactic acid) (PLA) conjugate at three different ratios (CIP@GC(PLA) NPs (1:1,5,15)) were fabricated. CIP@GC(PLA) NPs (1:1) were more effective than other tested ratios, indicating the importance of optimal hydrophobic/hydrophilic balance for corneal penetration and preventing bacterial invasion. The CIP@GC(PLA) (NPs) (1:1) realized the highest association with human corneal epithelial cells, which were nonirritant to the hen's egg-chorioallantoic membrane test (HET-CAM test) and demonstrated significant antibacterial response in the in vitro minimum inhibitory, bactericidal, live-dead cells, zone of inhibition, and biofilm inhibition assays against the keratitis-inducing pathogen Pseudomonas aeruginosa. The antiquorum sensing activity of GC has been explored for the first time. The NPs disrupted the bacterial quorum sensing by inhibiting the production of virulence factors, including acyl homoserine lactones, pyocyanin, and motility, and caused significant downregulation of quorum sensing associated genes. In the in vivo studies, CIP@GC(PLA) NPs (1:1) displayed ocular retention in vivo (∼6 h) and decreased the opacity and the bacterial load effectively. Overall, the CIP@GC(PLA) NP (1:1) is a biofilm-disrupting antiquorum sensing treatment regimen with clinical translation potential in BK.

Preparation, Characterization, and Antiangiogenic Evaluation of a Novel 5-Fluorouracil Derivative Solid Lipid Nanoparticle with a Hen's Egg Chorioallantoic Membrane Assay and Wound Healing Response in HaCaT Keratinocytes.

5-Fluorouracil is a heterocyclic aromatic organic compound, and it is commonly used as a chemotherapeutic agent in many cancers. The present goal is to analyze and characterize the physicochemical and biological properties of a new therapeutic formulation of 5-FUD-Gal under simulated chronic wound and oxidative stress conditions. After synthesis of a new 5-fluorouracil derivative, preparation and characterization of the formulation were carried out. The antiangiogenic effect, wound healing, and oxidative stress responses were conducted with a HET-CAM assay and in vitro cell culture technique. The results initially demonstrated that 5-FUD-Gal synthesized by a series of reactions and the SLN formulation were prepared successfully. A strong cell protective effect above 98% cell viability was detected at 20 μM at 48 h. The wound closure of the HaCaT scratch assay was calculated to be 90.12 and 98.98% at 10 and 20 μM concentrations, respectively, at 48 h. Moreover, the strongest effect of 5-FUD-Gal-F was observed at 20 μM concentration on chicken embryos. This study provides novel insights that a new derivative of semisynthetic 5-FUD-Gal-F can be further evaluated as a therapeutic chemical compound in cancer disease.

The potential of Paeonia lactiflora pall seeds oil as a pure natural cosmetics raw material: InVitro findings.

As a traditional Chinese herbal medicine, Paeonia lactiflora Pall is rich in various active ingredients such as polysaccharides and total flavonoids while having ornamental value. It has potential application value in the development of food and cosmetics. To study the invitro efficacy of Paeonia lactiflora Pall seeds oil. Firstly, the levels of linolenic acid and linoleic acid in Paeonia lactiflora Pall seeds oil were quantified using gas chromatography. The impact of Paeonia lactiflora Pall seeds oil on the proliferation rate of B16F10 cells was assessed through the CCK-8 method, while the melanin content of B16F10 cells was determined using the sodium hydroxide lysis method. The inhibitory effects of Paeonia lactiflora Pall seeds oil on elastase, collagenase and hyaluronidase were evaluated by biochemical techniques invitro. Lastly, the hen's egg chorioallantoic membrane test (HET-CAM) was conducted to confirm the absence of eye irritation caused by Paeonia lactiflora Pall seeds oil. Paeonia lactiflora Pall seeds oil within a certain volume concentration range (0.5%-4%) had no effect on the proliferation of B16F10 cells. Paeonia lactiflora Pall seeds oil showed significant inhibition of elastase, collagenase and hyaluronidase. Notably, the highest concentration tested, 4% Paeonia lactiflora Pall seed oil, yielded the most pronounced outcomes without causing any irritation. A certain concentration of Paeonia lactiflora Pall seeds oil has a significant effect on decreasing the melanin content in B16F10 cells and inhibiting the activities of elastase, collagenase, and hyaluronidase, which can provide a reference for the development of pure natural cosmetics raw materials.

Acheta domesticus: A Natural Source of Anti-Skin-Aging Ingredients for Cosmetic Applications.

Acheta domesticus is an edible insect, rich in nutritional value and considered a sustainable protein source. This study aimed to investigate the potential application of A. domesticus extracts for anti-skin-aging purposes. The extracts were prepared by maceration at ambient temperature with 95% ethanol or hexane and maceration in gentle heat (45 °C) with 95% v/v ethanol or DI water. The extracts were examined for total protein, phenolic, and flavonoid contents. Protein molecular weight distribution was analyzed. The safety of the extracts was investigated in terms of irritation and cytotoxicity. Biological activities relevant to the inhibition of skin aging were evaluated, including increasing transforming growth factor-beta 1 (TGF-β1) expression and inhibitory activities on collagenase and hyaluronidase. The aqueous extract from maceration in gentle heat had the highest total protein content (63 ± 1% w/w), total phenolic content (0.48 ± 0.03 mg GAE/g extract), TGF-β1 stimulating activities (33 ± 2 pg/mL), and collagenase inhibition (with a half maximal inhibitory concentration of 26 ± 1 µg/mL) among various extracts investigated. It caused no irritation to the hen's egg chorioallantoic membrane and showed no cytotoxicity to human dermal fibroblasts and peripheral blood mononuclear cells. Therefore, aqueous A. domesticus extract is proposed as an innovative natural anti-skin-aging ingredient.

Unlocking the beauty benefits: Exploring biosurfactants from Scheffersomyces shehatae for cosmetics

AbstractAs the cosmetic market continues to transform, innovative ingredients such as biosurfactants (BS) emerge as a fundamental step towards a generation of cosmetic products characterized by efficacy, safety, and environmental responsibility. In alignment with the global push towards natural, renewable, and non‐toxic materials, BS stands out as an interesting alternative to conventional synthetic surfactants. BS are a type of green surfactants and compared to synthetic surfactants derived from petroleum they are more biodegradable and have low or no toxicity. This work aimed to investigate the suitability of a biosurfactant extracted from the yeast Scheffersomyces shehatae (BS‐SS) to be used in cosmetic applications. The cytotoxicity of the BS‐SS was tested in fibroblast (L929) and keratinocyte (HaCaT) cell lines and the potential for ocular irritation was assessed by the hen's egg chorioallantoic membrane test (HET‐CAM). The cleaning efficiency of the BS‐SS was measured as the ability of make‐up removal in pig skin. Our results showed that the IC 50 values were 10.49 mg/mL for fibroblasts and 11.77 mg/mL for keratinocytes, and the biosurfactant did not result in hemorrhage, lysis, and coagulation damages in the chorioallantoic membrane, which classifies the biosurfactant solution as non‐irritant. Therefore, ocular toxicity and in vitro skin cell toxicity results showed that BS‐SS can be tolerable and safe for cosmetic purposes. BS‐SS featured promising cleaning properties, similar to the cleansing activity of the 1% SDS solution and of micellar water for lipstick and foundation products. In conclusion, the results indicate its potential use in cosmetic applications.

Promising Anti-Wrinkle Applications of Aromatic Extracts of Hedychium coronarium J. Koenig via Antioxidation and Collagenase Inhibition.

This study aimed to extract aromatic compounds from the rhizomes, leaf sheaths, and leaves of Hedychium coronarium and investigate their chemical compositions, cosmetic/cosmeceutical activities, and irritation potency. The chemical compositions were investigated via gas chromatography-mass spectrometry. The antioxidant activities were evaluated via spectrophotometry. The anti-skin wrinkle properties were investigated via collagenase, elastase, and hyaluronidase inhibition. The irritation potency was observed via a hen's egg-chorioallantoic membrane test. Eucalyptol was detected as a major component in the rhizomes and leaf sheaths, while β-caryophyllene was predominant in the leaves. The absolutes from the rhizomes were the strongest antioxidants, with ABTS scavenging properties similar to L-ascorbic acid. Interestingly, the equivalent concentration (EC1) of the absolute from the rhizome was 0.82 ± 0.01 µg FeSO4/g extract, which was significantly more potent than L-ascorbic acid (0.43 ± 0.03 µg FeSO4/g extract). The rhizome-derived absolute was the most effective against collagenase, while the concretes from the rhizomes and leaf sheaths showed promising anti-hyaluronidase activity with inhibitions of 90.5 ± 1.6% and 87.4 ± 5.1%, respectively. The irritability of the aromatic extracts was not different from that of the vehicle control, proving their safety. Therefore, the Hedychium coronarium rhizome-derived absolute was an attractive and potent antioxidant with anti-collagenase activities, indicating its potential for use in anti-aging formulations.

Ocular antibacterial chitosan-maleic acid hydrogels: In vitro and in vivo studies for a promising approach with enhanced mucoadhesion

The aim was to design and evaluate a chitosan-based conjugate providing high mucoadhesiveness and antibacterial activity for ocular infections treatment. Chitosan was conjugated with maleic acid via amide bond formation and infrared spectroscopy. Furthermore, 2,4,6-Trinitrobenzene sulfonic acid (TNBS) allowed characterization and quantification of conjugated groups, respectively. Biocompatibility was tested via hemolysis assay and Hen's Egg-Chorioallantoic membrane test. Characterization of the pH and osmolarity of hydrogels was followed by mucoadhesion assessment utilizing rheology. In addition, antibacterial studies were carried out towards Escherichia coli by broth microdilution test and agar-disk diffusion assay. In vivo studies were carried out following the already established Draize test and determining pharmacokinetic profile of dexamethasone in aqueous humour. The conjugate exhibited a degree of modification of 50.05 % and no toxicity or irritability. Moreover, mucoadhesive properties were enhanced in 2.68-fold and 1.81-fold for elastic and viscous modulus, respectively. Furthermore, rheological synergism revealed the presence of a gel-like structure. Additionally, broth microdilution and agar disk diffusion studies exhibited enhancement in antibacterial activity. Finally, in vivo studies manifested that hydrogels were highly tolerated, evidencing promising characteristics of the developed conjugate. The conjugate presented promising antimicrobial, long lasting mucoadhesive features and highly improved pharmacokinetics, leading to a revolutionizing approach in the treatment of ocular bacterial infections.

Influence of Benincasa hispida Peel Extracts on Antioxidant and Anti-Aging Activities, including Molecular Docking Simulation.

Benincasa hispida peel, a type of postconsumer waste, is considered a source of beneficial phytochemicals. Therefore, it was subjected to investigation for biological activities in this study. B. hispida peel was extracted using 95% v/v, 50% v/v ethanol and water. The obtained extracts were B95, B50 and BW. B95 had a high flavonoid content (212.88 ± 4.73 mg QE/g extract) and phenolic content (131.52 ± 0.38 mg GAE/g extract) and possessed high antioxidant activities as confirmed by DPPH, ABTS and lipid peroxidation inhibition assays. Moreover, B95 showed inhibitory effects against collagenase and hyaluronidase with values of 41.68 ± 0.92% and 29.17 ± 0.66%, which related to anti-aging activities. Via the HPLC analysis, one of the potential compounds found in B95 was rutin. Molecular docking has provided an understanding of the molecular mechanisms underlying the interaction of extracts with collagenase and hyaluronidase. All extracts were not toxic to fibroblast cells and did not irritate the hen's egg chorioallantoic membrane, which indicated its safe use. In conclusion, B. hispida peel extracts are promising potential candidates for further use as antioxidant and anti-aging agents in the food and cosmetic industries.

Exploring Penetration Ability of Carbonic Anhydrase Inhibitor-Loaded Ultradeformable Bilosome for Effective Ocular Application.

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6h and trans-corneal permeability of 8.78 ± 0.14cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.

A step ahead to enhancing routine breast cancer resection: Spheroid and hen's egg chorioallantoic membrane models to assess the photodynamic diagnosis efficiency of ALA and PSI-ALA-hex.

Aminolevulinic acid (ALA) and its derivatives have been used in the diagnosis of several diseases through topical, intravesical, and oral administration. However, their intravenous use for the theranostics of cancers has not raised interest despite its potential advantages. In this study, we compared the efficacy of ALA, its hexyl ester ALA-Hex, and our new derivative PSI-ALA-Hex to induce a fluorescent protoporphyrin IX (PpIX) overproduction in breast cancers. First, we tested the drugs on four subtypes of breast cancer spheroids in vitro. Our results demonstrated the capacity of ALA-Hex and PSI-ALA-Hex to produce PpIX in all breast spheroids, although ALA struggled in half of the models. We applied the chick embryo in vivo model to investigate the intravenous administration route of ALA and PSI-ALA-Hex, ALA-Hex being toxic. We engrafted breast cancer nodules having various hormonal profiles onto the chorioallantoic membrane of the eggs. They were all detected by fluorescence imaging with mild efficacy using PSI-ALA-Hex, which displayed a maximum selectivity of 2.2 to 2.9, whereas ALA showed a higher selectivity from 3.2 to 5.1 at 300μmol/kg. PSI-ALA-Hex was less appropriate for the diagnosis of breast cancer by intravenous administration. We show for the first time, to the best of our knowledge, the photodetection and imaging of a wide range of breast tumors in vivo upon intravenous treatment with ALA.

Enhanced Cosmeceutical Potentials of the Oil from Gryllus bimaculatus de Geer by Nanoemulsions.

This study aimed to extract the oil from Gryllus bimaculatus de Geer, evaluate its potential for cosmeceutical applications, and develop nanoemulsions to promote the cosmeceutical capabilities of the oil. G. bimaculatus oil was produced by the cold pressing method. Its fatty acid compositions were assessed by fatty acid methyl ester/gas chromatographic-mass spectrometry. The antioxidant activities of the oil were investigated in terms of radical scavengers, reducing power, and lipid peroxidation inhibition. The whitening effects were investigated through anti-tyrosinase activities, whilst the anti-aging effects were investigated through inhibition against collagenase, elastase, and hyaluronidase. The irritant effects were investigated by the hen's egg chorio-allantoic membrane test and the cytotoxicity assay in immortalized human epidermal keratinocytes and human foreskin fibroblast cells. The nanoemulsions were developed, characterized, and evaluated for their stability and cosmeceutical properties. G. bimaculatus oil, rich in linoleic acid (31.08 ± 0.00%), oleic acid (30.44 ± 0.01%), palmitic acid (24.80 ± 0.01%), and stearic acid (7.61 ± 0.00%), demonstrated promising cosmeceutical properties in terms of antioxidant, anti-tyrosinase, and anti-skin ageing activities. Besides, the oil was safe since it induced no irritation or cytotoxicity. G. bimaculatus oil was successfully developed into nanoemulsions, and F1, composed of 1% w/w G. bimaculatus oil, 1.12% w/w polysorbate 80, 0.88% w/w sorbitan oleate, and 97% w/w DI water, had the smallest internal droplet size (53.8 ± 0.6 nm), the narrowest polydispersity index (0.129 ± 0.010), and a pronounced zeta potential (-28.23 ± 2.32 mV). All cosmeceutical activities of the oil were significantly enhanced after incorporation in the nanoemulsions (p < 0.001), particularly the whitening effects. G. bimaculatus oil nanoemulsion was an attractive cosmeceutical formulation with potent whitening effects, along with antioxidant and anti-aging properties. Therefore, nanoemulsion technology was found to be an effective strategy for improving the cosmeceutical properties of G. bimaculatus oil.

Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8h (10.92 ± 3.95µg of curcumin washed for H-LNCc and 28.41 ± 24.47µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90min only (62.60 ± 4.72µg for LNCc and 52.08 ± 1.63µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Oil-free eye drops containing Cyclosporine A/cyclodextrin/PVA supramolecular complex as a treatment modality for dry eye disease

According to the global mapping of dry eye disease (DED), nearly 5 to 50 % of people suffer from DED, and this number is on the rise. The drug of choice Cyclosporine A (CsA) exhibits poor ocular bioavailability due to high molecular weight and lipophilicity. Moreover, formulations of CsA currently available are in the form of oil-based emulsions that are known to cause ocular irritation and pain. In this study, sulfobutylether-β-cyclodextrin (SBE-β-CD) based binary and ternary supramolecular complexes of CsA were developed as completely oil-free, and particle-free eye drops to treat DED. The physicochemical characterizations were supplemented with relevant in silico studies, to ascertain the findings. Further, the efficacy of the complexes was evaluated in the scopolamine-induced mouse model of DED. The complexation improved the CsA solubility by ~21-fold, with ~4-fold improvement in dissolution and transcorneal permeation. The non-irritancy and non-toxicity were confirmed by hen's egg chorioallantoic membrane assay and cytotoxicity assay using human corneal epithelial cells, respectively. The in vivo treatment with the ternary CD complex demonstrated better management of the dry eye supported by the tear volume assessment, corneal fluorescein staining, and histopathological studies of the cornea, lacrimal gland, and harderian gland. The study demonstrates the potential of the supramolecular complex as an alternative to the oil-based formulation of eye drops for drugs that show low solubility and poor corneal permeation.

Potential cosmeceutical lamellar liquid crystals containing black longan (Dimocarpus longan Lour.) seed extract for MMP-1 and hyaluronidase inhibition

The aims of this study were to evaluate the biological activities of black Dimocarpus longan Lour. seed extracts and develop a lamellar liquid crystal (LLC). Different solvents, including petroleum ether, ethyl acetate, and 95% v/v ethanol, were used in the maceration of black D. longan seeds. The inhibitory activities on matrix metalloproteinase-1 (MMP-1) and hyaluronidase were evaluated. The irritating potency of D. longan seed extracts was determined using the hen's egg chorioallantoic membrane test. The extract with the strongest anti-ageing activities and no irritant impact was examined for its chemical contents using high-performance liquid chromatography and incorporated into the LLC. Various factors affecting the LLC formulations, including surfactant types and amounts, thickening agent types and amounts, and various oil types, were investigated. The results demonstrated that the ethyl acetate extract (EtOAc) was the most potent inhibitor of MMP-1 (IC50 = 21.7 ± 5.4 µg/mL) and hyaluronidase (oleanolic acid equivalent = 0.44 ± 0.03 g per g extract). Interestingly, its MMP-1 inhibition was equivalent to that of oleanolic acid, corilagin, and gallic acid. Furthermore, its hyaluronidase inhibition was equivalent to that of gallic acid and ellagic acid. Gallic acid, which was the most abundant compound (15.6% ± 0.06% w/w) was suggested as the compound responsible for the biological activities of EtOAc extract. Considering its potential anti-skin ageing properties with no irritation of EtOAc extract, it was incorporated into the most suitable LLC, which was composed of 5% w/w Lexfeel® D5 oil, 0.5% w/w Carbopol® U21, 2% w/w Liquid Crystal Cream Maker, and 92.5% w/w DI water. The LLC containing EtOAc extract presented birefringence under a polarizing light microscope, indicating its crystallinity. The formulation had good stability after heating–cooling cycles in terms of external appearance, crystallinity, viscosity, and pH (5.5). As a result, it is recommended as a potential cosmeceutical formulation for anti-skin wrinkling. It is proposed that more research be conducted on the safety and efficacy of the treatment on human volunteers.

Statistical optimization of voriconazole nanoparticles loaded carboxymethyl chitosan-poloxamer based in situ gel for ocular delivery: In vitro, ex vivo, and toxicity assessment.

The research study reflects the development of novel voriconazole (VCZ) loaded nanoparticles (NPs) for prolonged delivery for the management of ocular diseases. The in situ ophthalmic gel was prepared by incorporating NPs into carboxymethyl chitosan (CMCh) and poloxamer. The central composite design was used to optimize the process for the preparation of nanoparticles by the o/w solvent evaporation method. The developed nanoparticles were evaluated for the encapsulation efficiency (89.6 ± 1.2%), particle size (219.3 ± 1.8nm), polydispersity index (PDI, 0.1), zeta potential (- 21.1 ± 1.12mV), saturation solubility, DSC study, and drug release. The etherification process grafts carboxyl surface functional groups, on chitosan, and was confirmed by FTIR and NMR studies. The developed CMCh-poloxamer based gelling system was found to be clear and transparent with gelation temperature varying from 33 to 40°C. The nanoparticle-loaded gel containing CMCh demonstrated enhanced antifungal activity against Candida albicans. The optimized batch containing CMCh showed improved mucoadhesion by 2.86-fold compared to VCZ nanosuspension. The drug release was prolonged up to 8h with an ex vivo study suggesting the enhanced permeation across goat cornea estimated via fluorescent microscope. The hen's egg chorioallantoic membrane study revealed that the formulation was non-irritant and tolerated by the chorioallantoic membrane. The present study concludes that the VCZ loaded nanoparticulate in situ ophthalmic gel using CMCh may act as a potential alternative for traditional eye drops.

A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies

The incidence of corneal fungal infections continues to be a growing concern worldwide. Ocular delivery of anti-fungal drugs is challenging due to the anatomical and physiological barriers of the eye. The ocular bioavailability of ketoconazole (KTZ), a widely prescribed antifungal agent, is hampered by its limited aqueous solubility and permeation. In the study, the physicochemical properties of KTZ were improved by complexation with sulfobutylether-β-cyclodextrin (SBE-β-CD).KTZ-SBE-β-CD complex was studied in silico with docking and dynamics simulations, followed by wet-lab experiments.The optimized KTZ-SBE-β-CD complex was loaded into a thermosensitivein situ gel to increase corneal bioavailability. The supramolecular complex increased the solubility of KTZ by 5-folds and exhibited a 10-fold increment in drug release compared to the pure KTZ. Owing to the diffusion, thein situ gel exhibited a more sustained drug release profile. Theex vivocorneal permeation studies showed higher permeation from KTZ-SBE-β-CD in situ gel (flux of ∼19.11 µg/cm2/h) than KTZin situ gel (flux of ∼1.17 µg/cm2/h). The cytotoxicity assays and the hen's egg chorioallantoic membrane assay (HET-CAM) confirmed the formulations' safety and non-irritancy. In silico guided design of KTZ-SBE-β-CD inclusion complexes successfully modified the physicochemical properties of KTZ. In addition, the loading of the KTZ-SBE-β-CD complex into an in situ gel significantly increased the precorneal retention and permeation of KTZ, indicating that the developed formulation is a viable modality to treat fungal keratitis.