High Encapsulation Capacity Research Articles

Cellular Uptake of Phase-Separating Peptide Coacervates.

Peptide coacervates self-assembling via liquid-liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non-cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, identify the key steps by which droplets enter the cell. find that the uptake follows a non-canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia-like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge- and cholesterol-dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors - interfering with actin and tubulin polymerization - confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non-specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate-based strategies for intracellular delivery of macromolecular therapeutics.

Trailblazing 3D MOFs Featuring 1,2,4‐Dinitrimino Triazole: Redefining Energetic Materials and Iodine Encapsulation

AbstractThe quest for high‐performance energetic materials for defense and aerospace has intensified, focusing on balancing energy output and safety. This study presents the synthesis of 3D energetic metal‐organic frameworks (EMOFs) [Na3(DNT)(H2O)]n (Na‐MOF), [K2(DNT)2(H2O)]n (K‐MOF), and [Cs2(DNT)]n (Cs‐MOF) using 1,2,4‐dinitrimino triazole (DNT) through a hydrothermal process. The synthesized EMOFs are characterized using infrared spectroscopy, powder X‐ray diffraction, scanning electron microscopy (SEM), elemental analysis, and thermogravimetric analysis and differential scanning calorimetry, and structures confirmed via single‐crystal X‐ray diffraction, revealing 3D frameworks with crystal densities of 2.15, 2.16, and 2.86 g cm−3, respectively. Among them, Na‐MOF exhibits excellent detonation performance (VOD = 8900 m s−1, DP = 26.21 GPa), high thermal stability (Td = 369 °C), and insensitivity to impact and friction (IS = 40 J, FS = 360 N). K‐MOF displays balanced energetic and mechanical properties, while Cs‐MOF, though moderate in energetic performance, shows significant potential in pyrotechnic applications, producing a bright red flame. Intermolecular interactions are analyzed through Hirshfeld surface, 2D fingerprint, and SEM analyses, enhancing the understanding of particle size and morphology. Na‐MOF also demonstrates high iodine encapsulation capacity, positioning it as a potential replacement for traditional materials like RDX and heat‐resistant explosives such as HNS, with comparability to PYX.

Encapsulation of β-carotene in Pickering emulsions stabilized by self-aggregated chitosan nanoparticles: Factors affecting β-carotene stability

For conventional emulsions used to encapsulate easily degradable bioactive compounds, achieving small droplet size and high encapsulation capacity is a challenging. Pickering emulsions stabilized by self-aggregated chitosan particles may offer high encapsulation efficiency due to the robust mechanical barrier formed by solid particles adsorbed at the oil-water interface. Therefore, the effects of pH, chitosan concentration, oil volume fraction, homogenization pressure, and homogenization cycle on the stability of chitosan Pickering emulsions and the degradation of β-carotene were investigated. Effective interfacial adsorption of chitosan nanoparticles and moderate homogenization intensity facilitated the formation of small emulsion droplets. Unlike conventional emulsions, chitosan Pickering emulsions with smaller droplets provided enhanced protection for β-carotene. This enhancement was primarily attributed to the improved interfacial coverage of chitosan nanoparticles with smaller droplet sizes, which was advantageous for β-carotene protection. The optimal conditions for preparing β-carotene-loaded chitosan Pickering emulsions were as follows: pH 6.5, chitosan concentration of 1.0 wt%, oil volume fraction of 20 %, homogenization pressure of 90 MPa, and 6 homogenization cycles. These findings indicate that chitosan Pickering emulsions are well-suited for encapsulating β-carotene with both small droplet size and high encapsulation efficiency.

Antibacterial and antibiofilm potentials of vancomycin-loaded niosomal drug delivery system against methicillin-resistant Staphylococcus aureus (MRSA) infections

The threat of methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide, making it significantly necessary to discover a novel way of dealing with related infections. The quick spread of MRSA isolates among infected individuals has heightened public health concerns and significantly limited treatment options. Vancomycin (VAN) can be applied to treat severe MRSA infections, and the indiscriminate administration of this antimicrobial agent has caused several concerns in medical settings. Owing to several advantageous characteristics, a niosomal drug delivery system may increase the potential of loaded antimicrobial agents. This work aims to examine the antibacterial and anti-biofilm properties of VAN-niosome against MRSA clinical isolates with emphasis on cytotoxicity and stability studies. Furthermore, we aim to suggest an effective approach against MRSA infections by investigating the inhibitory effect of formulated niosome on the expression of the biofilm-associated gene (icaR). The thin-film hydration approach was used to prepare the niosome (Tween 60, Span 60, and cholesterol), and field emission scanning electron microscopy (FE-SEM), an in vitro drug release, dynamic light scattering (DLS), and entrapment efficiency (EE%) were used to investigate the physicochemical properties. The physical stability of VAN-niosome, including hydrodynamic size, polydispersity index (PDI), and EE%, was analyzed for a 30-day storage time at 4 °C and 25 °C. In addition, the human foreskin fibroblast (HFF) cell line was used to evaluate the cytotoxic effect of synthesized niosome. Moreover, minimum inhibitory and bactericidal concentrations (MICs/MBCs) were applied to assess the antibacterial properties of niosomal VAN formulation. Also, the antibiofilm potential of VAN-niosome was investigated by microtiter plate (MTP) and real-time PCR methods. The FE-SEM result revealed that synthesized VAN-niosome had a spherical morphology. The hydrodynamic size and PDI of VAN-niosome reported by the DLS method were 201.2 nm and 0.301, respectively. Also, the surface zeta charge of the prepared niosome was − 35.4 mV, and the EE% ranged between 58.9 and 62.5%. Moreover, in vitro release study revealed a sustained-release profile for synthesized niosomal formulation. Our study showed that VAN-niosome had acceptable stability during a 30-day storage time. Additionally, the VAN-niosome had stronger antibacterial and anti-biofilm properties against MRSA clinical isolates compared with free VAN. In conclusion, the result of our study demonstrated that niosomal VAN could be promising as a successful drug delivery system due to sustained drug release, negligible toxicity, and high encapsulation capacity. Also, the antibacterial and anti-biofilm studies showed the high capacity of VAN-niosome against MRSA clinical isolates. Furthermore, the results of real-time PCR exhibited that VAN-niosome could be proposed as a powerful strategy against MRSA biofilm via down-regulation of icaR gene expression.

Characterization and application of targeted MnO2/CS@ALA-MTX nano-radiosensitizers for boosting X-ray radiotherapy of brain tumors

The current study aimed to investigate the potential of methotrexate (MTX) functionalized, 5-aminolevulinic acid (5-ALA)-modified, chitosan-coated manganese dioxide (MnO2/CS) nanoparticles (NPs) as a targeted radiosensitizer for cancer therapy. The novelty of the current study lies in the development of the MnO2/CS@5-ALA-MTX NPs as a novel formulation with high encapsulation capacity, site specificity, and biosafety for targeted drug delivery. The study also emphasizes comprehensive in-vitro tests to understand the cell death mechanisms after radiosensitization. The effects of MnO2/CS@5-ALA-MTX NPs on U87MG cell lines treated with radiation were examined in-vitro and in-vivo. Mitochondrial function and reactive oxygen species (ROS) production were evaluated under normoxia and hypoxia conditions. The combination of MTX and 5-ALA provided tumor-targeting ability, while the CS coating prolonged the circulation time of the nano-system. The synthesized MnO2/CS@5-ALA-MTX NPs had an average size of 70 ± 9 nm, a Zeta potential of −6 ± 2 mV, and a polydispersity of 0.240. The loading efficiency and release profile of the drug delivery system were assessed and demonstrated its capacity for drug delivery. The MTT assay on U87MG cells revealed that MnO2/CS@5-ALA-MTX NPs reduced cell viability compared to MTX alone. Both in-vitro and in-vivo studies demonstrated tumor-enhanced radiosensitization using MTX functionalized MnO2/CS NPs. The mice receiving MnO2/CS@5-ALA-MTX NPs and subsequent radiation exposure exhibited significant tumor inhibition and increased survival ratios. Notably, tumor-bearing mice treated with MnO2/CS@5-ALA-MTX NPs and X-ray irradiation demonstrated more effective tumor rejection compared to the groups treated with X-ray alone or NPs alone. In conclusion, the results highlight the potential of MnO2/CS@5-ALA-MTX NPs as a targeted radiosensitizer for cancer therapy. The NPs exhibited promising tumor-inhibiting effects and enhanced radiosensitization both in-vitro and in-vivo, suggesting their potential as a valuable approach for cancer treatment in the future.

Co-assembly of quinoa protein isolate and shellac as nano-vehicles for naringenin: Characterization, formation mechanism, release behavior and cellular uptake

Naringenin (Nar) is a natural flavonoid with diverse health-promoting benefits. However, the bioavailability of Nar is significantly restricted due to its poor water-solubility, instability under physiological conditions, and limited absorption profile. In this study, a shellac-quinoa protein isolate (QPI) binary nanocomplex (SQP) was fabricated using the pH-shifting method for effectively delivering Nar. Isothermal titration calorimetry (ITC) and analysis of inner interactive forces revealed that the complexation between QPI and shellac was primarily driven by electrostatic and hydrophobic forces. Subsequently, Nar was successfully encapsulated within the stable and uniform SQP nanocomplex (Nar@SQP), achieving a high encapsulation capacity (94.52 % encapsulation efficiency and 14.68 % loading capacity). Meanwhile, the Nar@SQP nanoparticle exhibited excellent stability against pH, ionic strength, and long-term storage. Moreover, it also demonstrated sustained and slow-release characteristics during simulated gastrointestinal digestion. Compared to free Nar, the safe Nar@SQP nanoparticle effectively facilitated the cellular uptake of encapsulated Nar by Caco-2 cells, suggesting that Nar@SQP has a good potential to improve the bioavailability of Nar. Hence, these findings indicated that the developed Nar@SQP nanoparticle might hold significant promise as a nano-delivery system for hydrophobic bioactive nutrients, like Nar.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.

Nanogel: Types, Methods of Preparation, Limitation, Evaluation and Application – A Systematic Review

Nanogels combine the characteristics of nanomaterials with hydrogels. To meet the expanding demands from various areas, a sizable number of nanogels have been designed and manufactured using the emulsion solvent diffusion nano precipitated method, emulsion evaporation of the solvent method, reverse micellar method and modified diffusion emulsification method. Thermosensitive nanogel, pH-sensitive nanogel, ultrasound-sensitive magnetic response, response to multiple stimuli, chain transfer polymerization, photo-induced crosslinking polymerization and modifications for active targeting are the types of nanogels based on response towards stimuli and polysaccharide, chitosan, pullulan, hyaluronic acid, alginate, cyclodextrin, gum acacia, protein are used to prepare nanogel. Nanogels have considerable potential and novelty within the biomedical sector due to their uniformity, adjustable dimensions, little toxicity, resilience in the presence of serum, and capacity for responsive behavior with a comparatively high drug encapsulation capacity. Nanogels have considerable potential in bioactive substance delivery, organ targeting, and chemotherapy. The article highlighted the preparation, types, evaluation and applicability of nanogel as a targeted delivery system.

PH-shifted quinoa protein isolate-based nanocarriers for naringenin: Structure characterization and stability evaluation

Naringenin (Nar) is an important natural flavonoid compound with multiple health functions, but stability issues and poor solubility greatly limit its bioavailability. To enhance the water-solubility, chemical stability and bioavailability of Nar, quinoa protein isolate (QPI)-Nar and pH-shifted QPI (PQPI)-Nar nanoparticles were constructed in this study. The results of ultraviolet–visible and fluorescence spectra showed there existed the interactions between QPI or PQPI and Nar, with stronger interaction between PQPI and Nar. Thermodynamic analysis indicated the molecular interactions between QPI or PQPI and Nar were mainly driven by hydrogen bonds. Circular dichroism (CD) and surface hydrophobicity results revealed that the binding of Nar changed the secondary structures and reduced surface hydrophobicity of QPI and PQPI. The measured DLS, LC and EE results suggested that PQPI-Nar nanoparticles formed a more stable system with higher encapsulation capacity. Additionally, PQPI-Nar nanoparticles exhibited higher antioxidant activity, superior slow-release property and biocompatibility, as well as better thermal and ultraviolet stability than QPI-Nar nanoparticles. These results indicated that PQPI-Nar nanoparticles could effectively improve the bioavailability of Nar. This study may provide a theoretical basis for the promising application of PQPI-Nar nanoparticle delivery systems in the food industry.

Hyaluronic Acid Nanogels: A Promising Platform for Therapeutic and Theranostic Applications.

Hyaluronic acid (HA) nanogels are a versatile class of nanomaterials with specific properties, such as biocompatibility, hygroscopicity, and biodegradability. HA nanogels exhibit excellent colloidal stability and high encapsulation capacity, making them promising tools for a wide range of biomedical applications. HA nanogels can be fabricated using various methods, including polyelectrolyte complexation, self-assembly, and chemical crosslinking. The fabrication parameters can be tailored to control the physicochemical properties of HA nanogels, such as size, shape, surface charge, and porosity, enabling the rational design of HA nanogels for specific applications. Stimulus-responsive nanogels are a type of HA nanogels that can respond to external stimuli, such as pH, temperature, enzyme, and redox potential. This property allows the controlled release of encapsulated therapeutic agents in response to specific physiological conditions. HA nanogels can be engineered to encapsulate a variety of therapeutic agents, such as conventional drugs, genes, and proteins. They can then be delivered to target tissues with high efficiency. HA nanogels are still under development, but they have the potential to become powerful tools for a wide range of theranostic or solely therapeutic applications, including anticancer therapy, gene therapy, drug delivery, and bioimaging.

In vitro evaluation and in vivo efficacy studies of a liposomal doxorubicin-loaded glycyrretinic acid formulation for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), more than 800 000 cases reported annually, is the most common primary liver cancer globally. Doxorubicin hydrochloride (Dox-HCl) is a widely used chemotherapy drug for HCC, but efficacy and tolerability are limited, thus critical to develop delivery systems that can target Dox-HCl to the tumour site. In this study, liver-targeting ligand glycyrrhetinic acid (Gly) was conjugated to polyethylene glycol (PEG) via Steglich reaction and incorporated in liposomes, which were then loaded with Dox-HCl by pH gradient method. The optimal formulation Gly–Peg-Dox-ProLP-F6 showed high Dox-HCl encapsulation capacity (90.0%±1.85%), low particle size (120 ± 3.2 nm). Gly–Peg-Dox-ProLP-F6 formulation demonstrated substantially greater toxicity against HCC cells than commercial Dox-HCl formulation (greater against 1.14, 1.5, 1.24 fold against Hep G2, Mahlavu and Huh-7 cells, respectively), but was 1.86-fold less cytotoxic against non-cancerous cell line AML-12. It increased permeability from apical to basolateral (A–B) approximately 2-fold. Gly–Peg-Dox-ProLP-F6 demonstrated superior antitumor efficacy in mouse liver cancer model as evaluated by IVIS. Isolated mouse liver tissue contained 2.48-fold Dox more than Dox-HCl after administration of Gly–Peg-Dox-ProLP-F6, while accumulation in heart tissue was substantially lower. This Gly–Peg-Dox-ProLP-F6 formulation may improve HCC outcomes through superior liver targeting for enhanced tumour toxicity with lower systemic toxicity.

Kinetically Controlled Star Copolymer Self-Assembly for Rapid Fabrication of Nanoparticles with High Encapsulation Capacity.

Rapid and scalable self-assembly of an amphiphilic 21-arm star copolymer, (polystyrene-block-polyethylene glycol)21 [(PS-b-PEG)21 ] in aqueous solution has been performed by reverse solvent exchange procedure. Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) reveal the formation of nanoparticles with narrow size distribution. Further investigation indicates a kinetically controlled self-assembly mechanism of the copolymers, in which the star topology of the amphiphilic copolymer and deep quenching condition by reverse solvent exchange are key to accelerate intrachain contraction of the copolymer during phase separation. When interchain contraction dominant over interchain association, nanoparticles with low aggregation number could be formed. Thanks to the high hydrophobic contents of the (PS-b-PEG)21 polymers, the resulted nanoparticles could encapsulate a high capacity of hydrophobic cargo up to 19.84 %. The kinetically controlled star copolymer self-assembly process reported here provides a platform for the rapid and scalable fabrication of nanoparticle with high drug loading capacity (LC), which may find broad range of applications in, for example drug delivery, nanopesticide.

The Role of Crosslinker Content of Positively Charged NIPAM Nanogels on the In Vivo Toxicity in Zebrafish.

Polymeric nanogels as drug delivery systems offer great advantages, such as high encapsulation capacity and easily tailored formulations; however, data on biocompatibility are still limited. We synthesized N-isopropylacrylamide nanogels, with crosslinker content between 5 and 20 mol%, functionalized with different positively charged co-monomers, and investigated the in vivo toxicity in zebrafish. Our results show that the chemical structure of the basic unit impacts the toxicity profile depending on the degree of ionization and hydrogen bonding capability. When the degree of crosslinking of the polymer was altered, from 5 mol% to 20 mol%, the distribution of the positively charged monomer 2-tert-butylaminoethyl methacrylate was significantly altered, leading to higher surface charges for the more rigid nanogels (20 mol% crosslinker), which resulted in >80% survival rate (48 h, up to 0.5 mg/mL), while the more flexible polymers (5 mol% crosslinker) led to 0% survival rate (48 h, up to 0.5 mg/mL). These data show the importance of tailoring both chemical composition and rigidity of the formulation to minimize toxicity and demonstrate that using surface charge data to guide the design of nanogels for drug delivery may be insufficient.

Fabrication of Sacha Inchi Oil-Loaded Microcapsules Employing Natural-Templated Lycopodium clavatum Spores and Their Pressure-Stimuli Release Behavior.

Polymeric particles have attracted vast attention for use in various fields, especially as drug carriers and cosmetics, due to their excellent ability to protect active ingredients from the environment until reaching a target site. However, these materials are commonly produced from conventional synthetic polymers, which impose adverse effects on the environment due to their non-degradable nature, leading to waste accumulation and pollution in the ecosystem. This work aims to utilize naturally occurring Lycopodium clavatum spores to encapsulate sacha inchi oil (SIO), which contains active compounds with antioxidant activity, by applying a facile passive loading/solvent diffusion-assisted method. Sequential chemical treatments by acetone, potassium hydroxide, and phosphoric acid were employed to remove native biomolecules from the spores before encapsulation effectively. These are mild and facile processes compared to other synthetic polymeric materials. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed the clean, intact, and ready-to-use microcapsule spores. After the treatments, the structural morphology of the treated spores remained significantly unchanged compared to the untreated counterparts. With an oil/spore ratio of 0.75:1.00 (SIO@spore-0.75), high encapsulation efficiency and capacity loading values of 51.2 and 29.3%, respectively, were obtained. Using antioxidant assay (DPPH), the IC50 of SIO@spore-0.75 was 5.25 ± 3.04 mg/mL, similar to that of pure SIO (5.51 ± 0.31 mg/mL). Under pressure stimuli (1990 N/cm3, equivalent to a gentle press), a high amount of SIO was released (82%) from the microcapsules within 3 min. At an incubation time of 24 h, cytotoxicity tests showed a high cell viability of 88% at the highest concentration of the microcapsules (10 mg/mL), reflecting biocompatibility. The prepared microcapsules have a high potential for cosmetic applications, especially as functional scrub beads in facial washing products.

Formulated chitosan-sodium tripolyphosphate nanoparticles for co-encapsulation of ellagic acid and anti-inflammatory peptide: characterization, stability and anti-inflammatory activity.

Chitosan (CS) and tripolyphosphate (TPP) can be combined in the development of a material with synergistic properties and promising potential for the conservation of food products. In this study, ellagic acid (EA) and anti-inflammatory peptide (FPL)-loaded CS nanoparticles (FPL/EA NPs) were prepared using the ionic gelation method and optimal preparation conditions were obtained through a single factor design. The synthesized nanoparticles (NPs) were characterized using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Nanoparticles were spherical, with an average size of 308.33 ± 4.61 nm, a polydispersity index (PDI) of 0.254, a zeta potential of +31.7 ± 0.08 mV, and a high encapsulation capacity (22.16 ± 0.79%). An in vitro release study showed that EA/FPL had a sustainable release from FPL/EA NPs. The stability of the FPL/EA NPs was evaluated for 90 days at 0, 25, and 37 °C. Significant anti-inflammatory activity of FPL/EA NPs was verified by nitric oxide (NO) and tumor necrosis factor-α (TNF-α) reduction. These characteristics support the use of CS nanoparticles to encapsulate EA and FPL and improve their bioactivity in food products. © 2023 Society of Chemical Industry.

Influence of Polycaprolactone Concentration and Solvent Type on the Dimensions and Morphology of Electrosprayed Particles.

Polycaprolactone (PCL) micro- and nanoparticles produced using the electrospraying technique present high drug encapsulation capacity, a controllable surface area, and a good cost-benefit ratio. PCL is also considered a non-toxic polymeric material with excellent biocompatibility and biodegradability. All these characteristics make PCL micro- and nanoparticles a promising material for tissue engineering regeneration, drug delivery, and surface modification in dentistry. In this study, PCL electrosprayed specimens were produced and analyzed to determine their morphology and size. Three PCL concentrations (2, 4, and 6 wt%) and three solvent types (chloroform (CF), dimethylformamide (DMF), and acetic acid (AA)) with various solvent mixtures ratios (1:1 CF/DMF, 3:1 CF/DMF, 100% CF, 1:1 AA/CF, 3:1 AA/CF, and 100% AA) were used while keeping the remaining electrospray parameters constant. SEM images followed by ImageJ analysis showed a change in the morphology and size of the particles among various tested groups. A two-way ANOVA demonstrated a statistically significant interaction (p < 0.001) between PCL concentration and solvents on the size of the particles. With the increase in the PCL concentration, an increase in the number of fibers was observed among all the groups. The morphology and dimensions of the electrosprayed particles, as well as the presence of fibers, were significantly dependent on the PCL concentration, choice of solvent, and solvent ratio.

Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus.

An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe3+ species were identified using diffuse reflectance spectroscopy. The large surface area (804 m2/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug's release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08-1 h), insulin/ferrisilicate ratios (0.125-1.0) and drug release rates at different pH were examined using the Korsmeyer-Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.

Influence of 1,3-diacylglycerol on physicochemical and digestion properties of nanoemulsions and its enhancement of encapsulation and bioaccessibility of hydrophobic nobiletin.

Lipid-based delivery systems are commonly used to encapsulate hydrophobic bioactive compounds for enhancing their bioaccessibility and bioavailability, especially for triacylglycerol (TAG) oil-based delivery systems. However, studies on the development of 1,3-diacylglycerol (DAG) oil-based delivery systems are rather limited. Herein, the influence of 1,3-DAG oil as a carrier oil on the properties of nanoemulsions and the bioaccessibility of encapsulated hydrophobic nobiletin (NOB) were investigated. High-purity 1,3-DAG (over 93% pure) was prepared by a combination of enzymatic esterification and ethanol crystallization. 1,3-DAG oil as a carrier oil could be used to formulate nanoemulsions with smaller droplet size, narrower size distribution and similar stability compared to TAG oil. Importantly, 1,3-DAG oil could efficiently encapsulate high-loading NOB (1.45 mg g-1) in nanoemulsions and significantly improve the bioaccessibility of NOB (above 80%), which is attributable to its massive lipolysis and higher encapsulation capacity than TAG oil. Moreover, the addition of the 1,3-DAG component in TAG oil significantly improved the properties of nanoemulsions and the loading and bioaccessibility of NOB, especially as the 1,3-DAG content was not less than 50%. The structure of lipids (DAG versus TAG) influenced the nanoemulsion properties and the bioaccessibility of encapsulated NOB. Based on the good properties of 1,3-DAG oil coupled with its health benefits, 1,3-DAG oil-based nanoemulsion delivery systems have great prospects for improving and extending emulsion properties and bioactivity as well as bioaccessibility enhancement.

Acid-Resistant Mesoporous Metal-Organic Frameworks as Carriers for Targeted Hypoglycemic Peptide Delivery: Peptide Encapsulation, Release, and Bioactivity.

Oral administration of bioactive peptides with α-glucosidase inhibitory activities is a promising strategy for diabetes mellitus. The wheat germ peptide Leu-Asp-Leu-Gln-Arg (LDLQR) has been previously proven to inhibit the activity of α-glucosidase efficiently. However, it is still difficult to transport the peptide to the intestine completely due to the harsh condition of the stomach. Herein, an acid-resistant zirconium-based metal-organic framework, NU-1000, was used to immobilize LDLQR with a high encapsulation capacity (92.72%) and encapsulation efficiency (44.08%) in only 10 min. The in vitro release results showed that the acid-stable NU-1000 not only effectively protected LDLQR from degradation in the presence of stomach acid and pepsin effectively but also ensured the release of encapsulated LDLQR under simulated intestinal conditions. Furthermore, LDLQR@NU-1000 could slow down the elevated blood sugar caused by maltose in mice and the area under blood sugar curve decreased by almost 20% when compared with the control group. The inflammatory factor (IL-1β, IL-6) in vivo and cell growth in vitro were almost the same between NU-1000 treatment and normal control groups. This study indicates NU-1000 is a promising vehicle for targeted peptide-based bioactive delivery to the small intestine.

Chitosan/dialdehyde starch hybrid in situ forming hydrogel for ocular delivery of betamethasone

Ocular drug therapy remains to be a major pharmaceutical challenge due to the presence of ocular barriers. The development of novel ophthalmic delivery systems is an immense necessity to overcome such biological and physiological barriers. Hydrophilic gels are considered an ideal candidate for such purposes owing to their favorable characteristics such as rapid in situ gelation, biodegradability, biocompatibility, and high encapsulation capacity. In the current study, we report on the development of an in situ forming composite hydrogel formulated using natural polymers, including dialdehyde starch (DAS) and chitosan (CS), to deliver betamethasone to the eye. The modification of starch and composite hydrogel structure was evaluated by FT-IR spectroscopy. The effect of the different ratios of CS to DAS on the gelation time, surface microstructure morphology, swelling ratio, rheological behavior, and in vitro degradation was evaluated. Our findings demonstrated that the high content of DAS could result in fast gelation, improved mechanical strength, larger pore size, and optimized degradation with a fast in vitro and ex vivo release rate. Furthermore, the developed composite hydrogel displayed excellent biocompatibility in cell models in vitro. Altogether, the obtained data suggest that the developed hydrogel-based delivery system could be well suited for local administration of betamethasone to control ocular inflammation and consequent complications.