Mean Zeta Potential Research Articles

Sucupira oleoresin-based doxorubicin pH-sensitive nanoemulsions: A potential nanomedicine approach to enhance the safety profile and anticancer activity

Plant derivatives-based nanocarriers as a matrix for delivery of chemotherapeutic drugs are capable of enhancing conventional antitumor drugs' cytotoxicity against cancer cells. Bearing in mind that the use of doxorubicin-loaded sucupira oleoresin nanoemulsions can play a significant role in increasing specificity, and efficacy, whilst improvement the chemotherapy safety profile we hypothesize that this nanocarrier may be a powerful alternative strategy for cancer therapy. Thus, the aimed of this research was to prepare and characterize this nanoemulsion, as well as assess the antitumor activity and toxicity in an experimental murine breast cancer model. In the first place, the phytocompounds present in sucupira oleoresin were identified by Liquid chromatography docked Orbitrap-mass spectrometer. Afterward, the doxorubicin-loaded sucupira oleoresin nanoemulsion was prepared using hot homogenization followed by ultrasonic calibration method. Then, nanoemulsions were characterized in terms of mean diameter, polydispersity, zeta potential, entrapment efficiency, and kinetic release. Toxicity and in vivo antitumor activity were also evaluated. The bioactive compounds found in sucupira oleoresin were terpenes, especially sesqui- and vouacapan diterpenes, which have a wide range of biological activities. The sucupira oleoresin nanoemulsions with or without doxorubicin were stable under refrigeration, monodisperse featuring an average size of around 60 nm, and negative zeta potential. High encapsulation doxorubicin content (98 %) was related to the ion-pair formed between doxorubicin and oleic acid. Stability studies in different biological media suggest that the proposed formulation can remain stable after intravenous administration. Meanwhile, the release outcomes indicate a pH-responsive profile. In vivo studies show that nanoemulsions with a combination of doxorubicin and oleoresin exhibit better efficacy and reduced effects on organs of potential toxicity such as the liver, heart, and intestine as well as less body weight loss likened to the free drug. Owing to promising results, we highlight that the doxorubicin-loaded sucupira oleoresin nanoemulsion could supply gain better insights for the combined breast cancer treatment.

Profiling of charge characteristics and effect of pH on charge dynamics in cyprinid milt

Electrostatic properties of milt have a huge bearing on the reproductive success of externally fertilizing freshwater fish species. Considering the global significance of carp in aquaculture, we explored the charge profile of milt of ten commercially important carp species for the first time. Mean zeta potential of milt ranged from (−) 33.86 mV in Cirrhinus mrigala to (−) 56.34 mV in Systomus sarana at pH 7.0. The effect of pH on milt characteristics was studied with Labeo rohita as the model species. Zeta potential reduced significantly upon exposure to low pH (4.0) and increased at alkaline pH (10.0). Fertilization rate was significantly reduced at acidic pH. Our results indicate that changes in milt zeta potential due to acidic pH is a significant factor in reduced reproductive success of externally fertilizing freshwater fish. While low concentration of proteases were detected in milt, it remained in a stable colloidal form even after incubation for 18 h at room temperature with no significant difference in the mean zeta potential at the end of incubation. This seminal work on milt zeta potential of carp will open several avenues in aquaculture and fisheries for productivity enhancement and conservation. Study of the electrostatic properties of milt can also help explain puzzling questions of ecology, such as migratory behavior.

Formulation and optimization of fisetin nanoemulsion for the treatment of Alzheimer's disease in rats: Pharmacokinetic and pharmacodynamic assessment

Fiestin (FS) is a polyphenolic flavonoid that possesses various neuroprotective effects by attenuating the levels of AChE enzyme, accumulated amyloid β, free radicals and neuroinflammation against Alzheimer's disease (AD). It is also helpful in reducing cellular senescence. However, FS suffers from a dissolution rate-limited oral bioavailability, and poor blood-brain barrier (BBB) permeability leading to decreased therapeutic efficacy. To address these challenges, an attempt has been made to formulate a nanoemulsion (NE) of FS using Box-Behnken design (BBD) as optimization tool. The optimized NE contained 10 mg of FS, 164 μL of Capmul MCM EP/NF® (oil), 618 μL of T80 (surfactant), 218 μL of Transcutol P®, (co-surfactant) and 4000 μL of distilled water. The optimized formulation resulted in a mean droplet size, drug loading, polydispersity index (PDI), and zeta potential (ZP) of 32 nm, 95.5 %, 0.26, and −15.99 mV, respectively. In the pharmacokinetic studies, FS-NE showed 9.2-fold increase in Cmax as compared to naïve FS. Relative oral bioavailability FS loaded in FS-NE was 842.93 %. Further the concentration of FS loaded in FS-NE was 8.81-fold higher in brain than naive FS. To evaluate pharmacodynamic effects, an aluminum chloride (AlCl3)-induced AD rat model was used. Cognitive functions were assessed using the Morris water maze and open field tests. The formulation showed dose-dependent effects. Rats treated with both, low and high doses of FS-NE (groups VI and VII) showed significant improvements (P < 0.001) in cognitive functions in AD-induced rats. The biochemical studies showed that FS-NE at both doses attenuated the levels of AChE enzyme, amyloid β, oxidative stress, and neuroinflammation. Results of histopathology indicated that FS-NE attenuated the degeneration of neurons in the cerebral cortex and hippocampus parts of the brain.

Mucoadhesive Itraconazole Nanocrystals With Precise Control of Surface Charge Incorporated to Chitosan Films for Buccal Drug Delivery

AbstractDrug delivery to mucosal tissues presents considerable challenges related to the complex nature of the mucus layer protecting such tissues. This aggravates when delivering hydrophobic drugs, often requiring incorporation of drugs to nanoparticles and use of mucoadhesive systems. This paper aimed to develop an antifungal chitosan (CHI)‐based film loading itraconazole (ITZ) nanocrystals (NCs) with precisely controlled surface charge for enhanced mucoadhesion. Cationic and anionic ITZ NCs are prepared using wet media milling with mean particle sizes and zeta potentials of 226.9 ± 1.4 nm and 234.0 ± 2.90 nm, and +15.4 ± 2.8 mV and −16.2 ± 1.3 mV, for the cationic and anionic NCs, respectively. Cationic ITZ‐NCs exhibits a higher affinity to mucin particles. NCs‐loaded films showed stronger mechanical properties and adhesiveness compared with ITZ powder‐loaded films. Physicochemical analysis reveals that crystalline properties of the ITZ are preserved, with no drug‐excipients interaction. A significantly higher amount of ITZ mucosal deposition is obtained from films containing NCs (1360.23 ± 718.73 µg cm−2) compared with that from films containing ITZ powder (58.83 ± 37.45 µg cm−2). This work demonstrates the feasibility of tailoring the NCs surface, with the resultant systems showing potential for the management of fungal infections in mucosal tissues.

Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29µg/mL to 16.54µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

Comparison of free vs. liposomal naringenin in white adipose tissue browning in C57BL/6j mice

Naringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and −27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin (p = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin.

A Newly Validated HPLC-DAD Method for the Determination of Ricinoleic Acid (RA) in PLGA Nanocapsules.

The assessment of ricinoleic acid (RA) incorporated into polymeric nanoparticles is a challenge that has not yet been explored. This bioactive compound, the main component of castor oil, has attracted attention in the pharmaceutical field for its valuable anti-inflammatory, antifungal, and antimicrobial properties. This work aims to develop a new and simple analytical method using high-performance liquid chromatography with diode-array detection (HPLC-DAD) for the identification and quantification of ricinoleic acid, with potential applicability in several other complex systems. The method was validated through analytical parameters, such as linearity, limit of detection and quantification, accuracy, precision, selectivity, and robustness. The physicochemical properties of the nanocapsules were characterized by dynamic light scattering (DLS) to determine their hydrodynamic mean diameter, polydispersity index (PDI), and zeta potential (ZP), via transmission electron microscopy (TEM) and quantifying the encapsulation efficiency. The proposed analytical method utilized a mobile phase consisting of a 65:35 ratio of acetonitrile to water, acidified with 1.5% phosphoric acid. It successfully depicted a symmetric peak of ricinoleic acid (retention time of 7.5 min) for both the standard and the RA present in the polymeric nanoparticles, enabling the quantification of the drug loaded into the nanocapsules. The nanocapsules containing ricinoleic acid (RA) exhibited an approximate size ranging from 309 nm to 441 nm, a PDI lower than 0.2, ζ values of approximately -30 mV, and high encapsulation efficiency (~99%). Overall, the developed HPLC-DAD procedure provides adequate confidence for the identification and quantification of ricinoleic acid in PLGA nanocapsules and other complex matrices.

Tityus stigmurus-Venom-Loaded Cross-Linked Chitosan Nanoparticles Improve Antimicrobial Activity.

The rapid resistance developed by pathogenic microorganisms against the current antimicrobial pool represents a serious global public health problem, leading to the search for new antibiotic agents. The scorpion Tityus stigmurus, an abundant species in Northeastern Brazil, presents a rich arsenal of bioactive molecules in its venom, with high potential for biotechnological applications. However, venom cytotoxicity constitutes a barrier to the therapeutic application of its different components. The objective of this study was to produce T. stigmurus-venom-loaded cross-linked chitosan nanoparticles (Tsv/CN) at concentrations of 0.5% and 1.0% to improve their biological antimicrobial activity. Polymeric nanoparticles were formed with a homogeneous particle size and spherical shape. Experimental formulation parameters were verified in relation to mean size (<180 nm), zeta potential, polydispersity index and encapsulation efficiency (>78%). Tsv/CN 1.0% demonstrated an ability to increase the antimicrobial venom effect against Staphylococcus aureus bacteria, exhibiting an MIC value of 44.6 μg/mL. It also inhibited different yeast species of the Candida genus, and Tsv/CN 0.5% and 1.0% led to a greater inhibitory effect of C. tropicalis and C. parapsilosis strains, presenting MIC values between 22.2 and 5.5 µg/mL, respectively. These data demonstrate the biotechnological potential of these nanosystems to obtain a new therapeutic agent with potential antimicrobial activity.

Investigation of Folate-Functionalized Magnetic-Gold Nanoparticles Based Targeted Drug Delivery for Liver: In Vitro, In Vivo and Docking Studies.

Magnetic nanoparticles used for targeted drug administration present a promising approach in cancer treatment owing to its notable advantages, such as targeted and enhanced encapsulation ability and improved bio protection compared with conventional drug delivery methods. Au shell-iron core nanoparticles (Fe3O4@Au) were manufactured by a chemical process, coated with dextran to encapsulate curcumin, and functionalized for precision drug delivery using folic acid to combat liver cancer. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, vibrational spectroscopy, and magnetometry were applied to assess the synthesis of the Fe3O4@Au-DEX-CU-FA compound. The mean size, zeta potential, and polydispersity of Fe3O4@Au-DEX-CU-FA were 63.3 ± 2.33 nm, -68.3 ± 1.78 mV, and 0.041 ± 0.008, respectively. Molecular docking models were created to examine the relationship between Fe3O4@Au-CU and BCL-XL, BAK, and to identify potential binding sites. The loading efficiency and release profile tests examined the medication delivery system's ability. MTT assay was subsequently utilized to determine the optimal dosage and therapeutic efficacy of Fe3O4@Au-DEX-CU-FA on cancer SNU-449 and healthy THLE-2 cell lines. Flow cytometry demonstrated that Fe3O4@Au-DEX-CU-FA effectively induced cancer cell death. Fe3O4@Au-DEX-FA showed a regulated release profile of free curcumin at 37 °C and pH values of 7.4 and 5.4. Real-time PCR revealed increased BAK expression and decreased BCL-XL expression. Nude tumor-bearing mice were used for in vivo experiments. Fe3O4@Au-DEX-CU-FA treatment dramatically reduced the swelling size compared with free CU and control treatments. It also resulted in a longer lifespan, expanded splenocyte proliferation, increased IFN-γ levels, and decreased IL-4 levels. The regular cells showed no cytotoxic effect compared with the cancer type, confirming that Fe3O4@Au-DEX-CU-FA maintained its potent anticancer actions. The data suggests that Fe3O4@Au-DEX-CU-FA possesses a promising potential as a therapeutic agent for combating tumors.

Fullerene C60 functionalized Sm2O3@Eu2O3 bimetallic oxides core shell nanocomposites for zeta potential and energy storage applications

Nanocomposites of Fullerene C60 (FC60) with lanthanide oxides show better energy storage properties compared with any of them alone. In the present research, we have synthesized FC60 (2, 5 and 10 wt%) anchored on Sm2O3@Eu2O3 bimetallic oxides by simple chemical precipitation method. The FC60:Sm2O3@Eu2O3 core shell nanocomposites (NCs) were characterized by XRD (X-ray diffraction), SEM (scanning electron microscopy), EDX (energy dispersive X-ray), UV–visible, XPS (X-ray photoelectron spectroscopy), and BET (Brunauer–Emmett–Teller) analytical methods. XRD studies revealed mixed phase of monoclinic and orthorhombic crystal structure with irregularly scattered small plate/flake like morphology agglomerated and formed as large grains. Electrochemical supercapacitive behaviour of Sm2O3@Eu2O3 bimetallic oxides showed specific capacitance (SCs) of 665.075F/g in 3 M KOH as electrolyte. The SCs of FC60 (5 wt% and 10 wt%):Sm2O3@Eu2O3 electrode material in 3 M KOH solution was found to be 795.92F/g and 1120F/g at a current density of 1 A/g (scan rate of 10 mV/s). FC60 (10 wt%):Sm2O3@Eu2O3 NCs showed excellent capacitive retention of 90.8 % after 10,000 cycles. The Zeta potential (ζ) studies of FC60:Sm2O3@Eu2O3 NCs showed decrease in the mean Zeta potential (ζ) from 34.23 mV to 11.97 mV with decrease in electrophoretic mobility (2.667 to 0.933 (μm cm/Vs)) attributed to the cationic nature of the FC60:Sm2O3@Eu2O3 NCs. The FC60:Sm2O3@Eu2O3 NCs with high cycle stability and charge density can be a better candidate for high energy storage devices, supercapacitor, dielectric related applications.

Development and optimization of thyme-pennyroyal essential oils based active nanostructured lipid carrier (NLC) containing saffron extract with antioxidant and antimicrobial properties

The saffron extract-loaded nanostructured lipid carrier (NLC) was synthesized by the double emulsion (W/O/W) method for application as a preservative to increase the oxidative and microbial stability of French dressing. The optimization of the NLC system was carried out using a combined D-optimal design methodology and effect of thyme (TEOs)/pennyroyal (PEOs) essential oils, and polyglycerol ester (PGE)/polyglycerol polyricinolate (PGPR) surfactants ratios (independent variables) were investigated on the mean particle size, polydispersity, zeta potential, and encapsulation efficacy (dependent variables). The optimal formulation (NLC opt) was obtained as 90/10 thyme/pennyroyal essential oils and 90/10 polyglycerol esters/polyglycerol polyricinoleate ratio, which resulted in the lowest PDI and particle size (0.38 and 66.87 nm respectively), highest zeta potential and encapsulation efficiency (−26.7 mV and %78.88 respectively). Different techniques including transmission electron microscopy (TEM), Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis were used for the characterization of structure and physicochemical properties of the different NLC systems and confirmed successful incorporation of SE into NLC. The DPPH test showed decrement of antioxidant activity during 30 days of storage and IC50 value was lower in the SE-NLC (0.68 mg/ml) than in the free extract. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests against S. aureus, E. coli, and P. aeruginosa indicated that the SE did not have antibacterial properties. However, NLC formulations showed antimicrobial effect due to the presence of TEOs and PEOs essential oils. Peroxide value of control sample was the highest (8/35 O2/kg) and it was the lowest (3.75 O2/kg) in French dressing with SE-NLC.

Co-delivery of Bcl-2 siRNA and doxorubicin using liposome-incorporated poly(ε-caprolactone) /chitosan nanofibers for the treatment of lung cancer

The small interfering RNA (siRNA) and chemotherapeutic drugs-incorporated liposome-nanofiber hybrid delivery system could inhibit tumor growth and decrease the adverse side effects. In the present study, doxorubicin (DOX) anticancer drug and Bcl-2 siRNA have been incorporated into the liposome-embedded chitosan-poly (ethylene oxide)/poly (ε-caprolactone) (CS/PEO/PCL) pH-sensitive nanofibrous hybrid formulation for treating lung cancer. The mean particle size & zeta potential of liposome, DOX-liposome, and DOX-Bcl-2-liposome were 130 ± 10 nm & 27.85 ± 1.65 mV, 155 ± 15 nm & 26.30 ± 1.3 mV, and 195 ± 30 nm &11.31 ± 0.65 mV, respectively. The average diameter of electrospun CS/PEO/PCL/DOX-siRNA-liposome simple and CS/PEO/PCL/DOX-siRNA-liposome core-shell nanofibers was 385 ± 80, and 485 ± 100 nm, respectively. The extended release of DOX and si-RNA (30 days) were achieved from DOX-Bcl-2-liposome-incorporated CS/PEO/PCL core-shell nanofibers. The maximum down-regulation of Bcl-2 siRNA, apoptosis of cancer cells, and reduction in the cell viability of A549 lung carcinoma cells were achieved using DOX-Bcl-2 liposome-incorporated CS/PEO/PCL core-shell nanofibers. The in vivo results indicated the maximum suppress of tumor growth without change in the body weight for the mice treated with DOX-Bcl-2 liposome-incorporated CS/PEO/PCL nanofibers. The obtained results demonstrated that the prepared hybrid delivery system presented a novel effective formulation for treating lung cancer.

Influence of archaeal lipids isolated from Aeropyrum pernix K1 on physicochemical properties of sphingomyelin-cholesterol liposomes

We investigated the influence of archaeal lipids (C25,25) isolated from thermophilic archaeon Aeropyrum pernix K1 on physicochemical properties of liposomes comprised of egg sphingomyelin (SM) and cholesterol (CH) using fluorescence emission anisotropy, calcein release studies, dynamic light scattering, transmissive electron microscopy and phase analysis light scattering. The 2 mol% addition of archaeal lipids enabled formation of small unilamellar vesicles by sonication while also having significant effect on reducing mean size, polydispersity index and zeta potential of C25,25/SM/CH vesicles. Increasing the ratio of C25,25 lipids in mixture of C25,25/SM/CH decreased lipid ordering parameter in dose dependent manner at different temperatures. We also demonstrated that adding 15 mol% C25,25 to SM/CH mixture will cause it to notably interact with fetal bovine serum which could make them a viable alternative adjuvant to synthetic ether-linked lipids in development of advanced liposomal vaccine delivery systems. The prospect of combining the proven strengths of SM/CH mixtures with the unique properties of C25,25 opens exciting possibilities for advancing drug delivery technologies, promising to yield formulations that are both highly effective and adaptable to a range of therapeutic applications.

Florfenicol core–shell composite nanogels as oral administration for efficient treatment of bacterial enteritis

To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core–shell composite nanogels in this study. The florfenicol core–shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, –22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core–shell composite nanogels were successfully prepared. Florfenicol core–shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core–shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core–shell composite nanogels. Therefore, the prepared florfenicol core–shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.

ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to −25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.

Limonene-enriched ultra-structural cubosomes to augment ocular delivery of a poorly water soluble anti-fungal drug: Fabrication, characterization, statistical optimization, in vivo corneal uptake and histopathological evaluation in rabbits

The target of this investigation was to obtain the composition of the optimized Fenticonazole nitrate (FCN)-loaded cubosomal formula that can prolong precorneal retention, increase corneal absorption, enhance corneal permeation, and anti-fungal efficacy of FCN. Cubosomes are bi-continuous structural vesicles fabricated using the hot emulsification technique in accordance with a 23-full factorial design. The selected fabrication factors were the concentration of the Lipid phase (X1), glyceryl monooleate: lipid phase stabilizer ratio (X2), and aqueous phase stabilizer types (X3). Whereas, the encapsulation efficiency percent (EE%), Mean particle size (PS), Polydispersity index (PDI), and Zeta potential (ZP) were chosen as measured responses. The numerical optimization criterion of the design expert software was utilized to select the optimized formula (Op) for extra investigations. The Op formula had EE% of 87.94 ± 0.7 %, PS of 249.75 ± 1.48 nm, and ZP of −34.25 ± 0.64 mV. The in vitro release study of the Op formula in comparison with FCN suspension showed a zero-order and controlled kinetic release behavior. Moreover, the results of the pH, refractive index, surface tension, and mucoadhesion study confirmed the superiority and the safety of the Op formula. Further, the ex vivo permeation study demonstrated a significant enhancement in the transcorneal permeation of the Op formula than FCN suspension by 2.69-fold. Besides, the in vivo corneal uptake confirmed the higher permeation of the Op formula in comparison with FCN suspension. Draize test and histopathological examination ensured the in vivo safety and tolerability of the Op formula. Overall, the previous findings ensured the efficacy of cubosomes in enhancing ocular retention, absorption, permeation, and bioavailability of FCN.

Physicochemical properties, photostability, and digestive characteristics of natural emulsion system fabricated by recombinant rice bran oil bodies for lutein ester delivery

Rice bran oil bodies (RBOBs), as natural oil-in-water emulsions, can be used as a good carrier for delivering hydrophobic functional ingredients. In this work, the lutein ester-loaded rice bran oil body (LRBOB) emulsions were successfully prepared by restructuring the RBOBs natural structure through heat treatment and high-pressure homogenization. The physicochemical properties, photostability, and in vitro digestion of LRBOB emulsions with different oil body concentrations were investigated. The LRBOB emulsion with 50% RBOBs had maximum lutein ester encapsulation efficiency (94%) with larger mean particle size (566.44 ± 18.05 nm) and zeta potential (−43.87 ± 0.8 mV), exhibiting good physical stability and an amorphous structure of lutein ester. Meanwhile, the emulsion droplets formed a network structure through mutual adsorption, as observed by CLSM. Moreover, the apparent viscosity of LRBOB emulsion was increased with the increase of RBOBs concentration, showing a shear thinning behavior. Within the linear viscoelastic range, the emulsions mainly displayed elastic rheological characteristics. Furthermore, the photooxidation studies showed that the LRBOB emulsion retained a maximum of 37% lutein ester after 96 h of UV irradiation, and the half-life was extended to 58.89 h. Meanwhile, a higher amount of RBOBs effectively reduced lipid and protein oxidation and minimized color difference, indicating that RBOBs could effectively improve the stability of lutein ester. Based on the results of in vitro simulated digestion, LRBOB emulsion showed higher free fatty acid release (32%) and lutein ester bioaccessibility (40.17%) in the adult model, but is not recommended for infant diets. This work will provide a new delivery vehicle for the utilization of raw lutein materials, expanding the potential applications of natural plant oil bodies.

In vitro and in vivo studies of ocular topically administered NLC for the treatment of uveal melanoma

Uveal melanoma is one of the most common and aggressive intraocular malignancies, and, due to its great capability of metastasize, it constitutes the most incident intraocular tumor in adults. However, to date there is no effective treatment since achieving the inner ocular tissues still constitutes one of the greatest challenges in actual medicine, because of the complex structure and barriers. Uncoated and PEGylated nanostructured lipid carriers were developed to achieve physico-chemical properties (mean particle size, homogeneity, zeta potential, pH and osmolality) compatible for the ophthalmic administration of (S)-(–)-MRJF22, a new custom-synthetized prodrug for the potential treatment of uveal melanoma. The colloidal physical stability was investigated at different temperatures by Turbiscan® Ageing Station. Morphology analysis and mucoadhesive studies highlighted the presence of small particles suitable to be topically administered on the ocular surface. In vitro release studies performed using Franz diffusion cells demonstrated that the systems were able to provide a slow and prolonged prodrug release. In vitro cytotoxicity test on Human Corneal Epithelium and Human Uveal Melanoma cell lines and Hen’s egg-chorioallantoic membrane test showed a dose-dependent cytotoxic effect of the free prodrug on corneal cells, whose cytocompatibility improved when encapsulated into nanoparticles, as also confirmed by in vivo studies on New Zealand albino rabbits. Antiangiogenic capability and preventive anti-inflammatory properties were also investigated on embryonated eggs and rabbits, respectively. Furthermore, preliminary in vivo biodistribution images of fluorescent nanoparticles after topical instillation in rabbits’ eyes, suggested their ability to reach the posterior segment of the eye, as a promising strategy for the treatment of choroidal uveal melanoma.

Mango (Mangifera indica) seeds and peel-derived hydrocolloids: Gelling ability and emulsion stabilization

Mango is a tropical fruit that is consumed worldwide and is distinguished by its sweet and juicy flesh. Unfortunately, the peels and seeds of mango fruit are often discarded despite the fact that they contain compounds that can be valorized for certain applications. In this study, a physicochemical and hydrodynamic characterization of hydrocolloids extracted from the peel and seeds of mango fruit was performed and the impact on the microstructure and rheological behavior of derived gels, as well as the ability to form emulsions, were analyzed. The physicochemical parameters and proximate compositions of the different samples showed that the hydrocolloids extracted from the seeds are rich in proteins whereas those from the peel are rich in carbohydrates. The molecular weights calculated from the hydrodynamic characterization (Mv) are 101515 g/mol and 102,580 g/mol for hydrocolloids extracted from the peel and seeds, respectively. Dispersions of these hydrocolloids in water produced hydrogels upon heating, which exhibited a shear thinning response that can be described by the Williamson model. The ability of these hydrocolloids to form thermally-induced strong gels was monitored and analyzed by means of curing tests. Throughout thermal treatments, the storage modulus showed a significant increase, especially at concentrations greater than 2.5 wt%. Mango seeds and peel-derived hydrocolloids are also able to stabilize o/w emulsions. Derived emulsions showed D50 mean diameters and zeta potential values (ζ) in the ranges from 10.04 to 82.52 μm and from -17.63 to -11.12 mV, respectively. On the basis of the observed rheological behavior of hydrogels and emulsion-forming ability, the hydrocolloids derived from mango seeds and peels possess suitable characteristics to be potentially implemented in diverse food matrices, offering functional and nutritional benefits to final consumer products.

Preparation and intestinal absorption mechanism of self-assembled nanoparticles of Herpetospermum caudigerum

In this experiment, the micro-precipitation method was used to prepare self-assembled nanoparticles of Herpetospermum caudigerum Wall.(MP-SAN). The process was optimized using average particle size and polydispersity index(PDI)as evaluation indexes. The mean particle size, PDI,zeta potential, and microstructure of MP-SAN were characterized. The intestinal absorption mechanism of dehydrodiconiferyl alcohol(DA)and herpetrione(Her)in MP-SAN was investigated through single-pass intestinal perfusion in rats. The optimized process parameters for producing MP-SAN were a stirring speed of 800 r·min~(-1),stirring time of 5 min, and rotary evaporation temperature of 40℃. The resulting MP-SAN exhibited a spherical-like structure and uniform morphology, with a mean particle size of(267.63±13.27) nm, a PDI of 0.062 0±0.043 9,and a zeta potential of(-46.18±3.66) mV. The absorption rate constant(K_a)and apparent permeability coefficient(P_(app))of DA in the ileal segment were significantly higher than those in the jejunal segment(P&lt;0.05). However, there was no significant difference in the absorption of Her between the ileal and jejunal segments. Intestinal absorption parameters of DA and Her tended to increase with increasing drug concentration. Specifically, the K_a and P_(app) of DA in MP-SAN in the high-concentration group were significantly higher than those in the low-concentration group(P&lt;0.01). The addition of verapamil, a P-glycoprotein inhibitor, did not significantly affect the intestinal absorption of DA and Her. However, the absorption of both DA and Her in MP-SAN was significantly increased by the addition of indomethacin(P&lt;0.05),suggesting that DA and Her may be substrates for multidrug resistance-associated protein 2.