Hyaluronic acid-poly(glyceryl)10-stearate nanoemulsion for co-delivery of fish oil and resveratrol: Enhancing bioaccessibility and antioxidant potency.

Hyaluronic acid (HA), an endogenous polysaccharide comprising alternating D-glucuronic acid and N-acetylglucosamine units, is renowned for its high hydrophilicity, biocompatibility, and biodegradability. These attributes have rendered HA invaluable across medical and drug delivery fields. HA can be altered through physical, chemical, or enzymatic methods to improve the properties of the modified substances. In this work, we synthesized a derivative via the esterification of HA with poly(glyceryl)10-stearate (PG10-C18), designated as HA-PG10-C18. This novel derivative was employed to fabricate a nano co-delivery system (HA-PG10-C18@Res-NE) for fish oil and resveratrol (Res), aiming to enhance their stability and bioaccessibility. An exhaustive investigation of HA-PG10-C18@Res-NE revealed that the HA-modified system displayed superior physicochemical stability, notably in withstanding oxidation and neutralizing free radicals. Moreover, in vitro simulated digestion underscored the system's enhanced bioaccessibility of Res and more efficient release of free fatty acids. These outcomes underscore the strategic advantage of HA in modifying PG10-C18 for nanoemulsion formulation. Consequently, HA-PG10-C18 stands as a promising emulsifier for encapsulating lipophilic bioactives in functional foods, nutraceuticals, and pharmaceuticals.

Enhanced bioavailability of curcumin amorphous nanocomposite prepared by a green process using modified starch.

Curcumin (Cur), a bioactive compound extracted from plants, has attracted widespread attention due to its multiple pharmacological activities. However, the low bioavailability due to the inherent limitations in water solubility, chemical stability, and permeability poses great challenges for realizing its clinical potentials. In the current study, octenyl succinic anhydride-modified starch (OSA-S), a renewable and biodegradable biopolymer, was employed to fabricate Cur amorphous composite nanoparticles (Cur/OSA-S NPs) through a solvent-free pH-driven method with the aim to enhance Cur's bioavailability by improving its solubility and stability. Cur/OSA-S NPs, with mean sizes of about 128.9 ± 8.6 nm, encapsulation efficiencies of about 90.0 %, and the drug loading capacities around 51.0 ± 0.2 %, were successfully prepared. Cur was found to be dispersed within the composite nanoparticles in amorphous state as confirmed by the XRD and DSC characterizations. In addition, Cur/OSA-S NPs offers excellent storage, thermal and light stability, excellent re-dispersibility, and approximately 92 times better solubility than the original Cur. Furthermore, studies of dissolution and the parallel artificial membrane permeability assay (PAMPA) confirmed enhanced dissolution rates and in vitro permeabilities of Cur/OSA-S NPs. Cancer cell viability and uptake experiments revealed that Cur/OSA-S NPs possessed more potent inhibitory effects on cancer cell proliferation compared to the raw Cur. The results obtained from the current study demonstrated the effectiveness of OSA-S for manufacturing Cur amorphous composite nanoparticles with enhanced solubility, stability, and permeability, which might be valuable for further development of Cur based products for treatment of various diseases.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Improved physicochemical stability of fish oil nanoemulsion via a dense interfacial layer formed by hyaluronic acid-poly(glyceryl)10-stearate.

This study aimed to synthesize a novel emulsifier, hyaluronic acid-poly(glyceryl)10-stearate (HA-PG10-C18), and employ it for the fabrication of nanoemulsions incorporating deep-sea fish oil to improve their apparent solubility and physicochemical stability. 1H NMR and FT-IR analyses indicated successful synthesis of HA-PG10-C18. Nanoemulsions of deep-sea fish oil loaded with HA-PG10-C18 (HA-PG10-C18@NE) were successfully fabricated by ultrasonic emulsification. The fixed aqueous layer thickness (FALT) of PG10-C18@NE and HA-PG10-C18@NE was determined and the FALT of both nanoemulsions was similar, while the surface density of HA-PG10-C18@NE (4.92 × 10-12 ng/nm2) is 60 % higher than that of PG10-C18@NE (3.07 × 10-12 ng/nm2). Notably, HA-PG10-C18@NE demonstrated an exceptional physicochemical stability when exposed to various stressed environmental conditions, especially its freeze-thaw stability. Moreover, after simulated in vitro digestion, the HA-PG10-C18@NE exhibited a comparatively greater liberation of free fatty acids (94.0 ± 1.7 %) when compared to the release observed in PG10-C18@NE (85.5 ± 2.2 %).

Hyaluronic Acid Poly(glyceryl)10-Stearate Derivatives: Novel Emulsifiers for Improving the Gastrointestinal Stability and Bioaccessibility of Coenzyme Q10 Nanoemulsions.

Fish oils are a rich source of polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid, which are reported to exhibit therapeutic effects in a variety of human diseases. However, these oils are highly susceptible to degradation due to oxidation, leading to rancidity and the formation of potentially toxic reaction products. The aim of this study was to synthesize a novel emulsifier (HA-PG10-C18) by esterifying hyaluronic acid with poly(glyceryl)10-stearate (PG10-C18). This emulsifier was then used to formulate nanoemulsion-based delivery systems to co-deliver fish oil and coenzyme Q10 (Q10). Q10-loaded fish oil-in-water nanoemulsions were fabricated, and then their physicochemical properties, digestibility, and bioaccessibility were measured. The results indicated that the environmental stability and antioxidant activity of oil droplets coated with HA-PG10-C18 surpassed those coated with PG10-C18 due to the formation of a denser interfacial layer that blocked metal ions, oxygen, and lipase. Meanwhile, the lipid digestibility and Q10 bioaccessibility of nanoemulsions formulated with HA-PG10-C18 (94.9 and 69.2%) were higher than those formulated with PG10-C18 (86.2 and 57.8%), respectively. These results demonstrated that the novel emulsifier synthesized in this study could be used to protect chemically labile fat-soluble substances from oxidative damage, while still retaining their nutritional value.

Dual role of polyglycerol vitamin E succinate in emulsions: An efficient antioxidant emulsifier.

α-Tocopherol, as an oil-soluble vitamin with strong antioxidant activity. It is the most naturally abundant and biologically active form of vitamin E in humans. In this study, a novel emulsifier (PG20-VES) was synthesized by attaching hydrophilic twenty-polyglycerol (PG20) to hydrophobic vitamin E succinate (VES). This emulsifier was shown to have a relatively low critical micelle concentration (CMC = 3.2 µg/mL). The antioxidant activities and emulsification properties of PG20-VES were compared with those of a widely used commercial emulsifier: D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS). PG20-VES exhibited a lower interfacial tension, stronger emulsifying capacity and similar antioxidant property to TPGS. An in vitro digestion study showed that lipid droplets coated by PG20-VES were digested under simulated small intestine conditions. This study showed that PG20-VES is an efficient antioxidant emulsifier, which may have applications in the formulation of bioactive delivery systems in the food, supplement, and pharmaceutical industries.

Design of a device for simultaneous particle size and electrostatic charge measurement of inhalation drugs.

PURPOSE: To develop a device for simultaneous measurement of particle aerodynamic diameter and electrostatic charge of inhalation aerosols. METHOD: An integrated system consisting of an add-on charge measurement device and a liquid impinger was developed to simultaneously determine particle aerodynamic diameter and electrostatic charge. The accuracy in charge measurement and fine particle fraction characterization of the new system was evaluated. The integrated system was then applied to analyze the electrostatic charges of a DPI formulation composed of salbutamol sulphate-Inhalac 230 dispersed using a Rotahaler. RESULTS: The charge measurement accuracy was comparable with the Faraday cage method, and incorporation of the charge measurement module had no effect on the performance of the liquid impinger. Salbutamol sulphate carried negative charges while the net charge of Inhalac 230 and un-dispersed salbutamol sulphate was found to be positive after being aerosolized from the inhaler. The instantaneous current signal was strong with small noise to signal ratio, and good reproducibility of charge to mass ratio was obtained for the DPI system investigated. CONCLUSIONS: A system for simultaneously measuring particle aerodynamic diameter and aerosol electrostatic charges has been developed, and the system provides a non-intrusive and reliable electrostatic charge characterization method for inhalation dosage forms.

Investigation of electrostatic behavior of a lactose carrier for dry powder inhalers.

PURPOSE: This study aims to elucidate the electrostatic behavior of a model lactose carrier used in dry powder inhaler formulations by examining the effects of ambient relative humidity (RH), aerosolization air flow rate, repeated inhaler use, gelatin capsule and tapping on the specific charge (nC/g) of bulk and aerosolized lactose. MATERIALS AND METHODS: Static and dynamic electrostatic charge measurements were performed using a Faraday cage connected to an electrometer. Experiments were conducted inside a walk-in environmental chamber at 25 degrees C and RHs of 20% to 80%. Aerosolization was achieved using air flow rates of 30, 45, 60 and 75 L/min. RESULTS: The initial charges of the bulk and capsulated lactose were a magnitude lower than the charges of tapped or aerosolized lactose. Dynamic charge increased linearly with aerosolization air flow rate and RH. Greater frictional forces at higher air flow rate induced higher electrostatic charges. Increased RH enhanced charge generation. Repeated inhaler use significantly influenced electrostatic charge due to repeated usage. CONCLUSIONS: This study demonstrated the significance of interacting influences by variables commonly encountered in the use DPI such as variation in patient's inspiratory flow rate, ambient RH and repeated inhaler use on the electrostatic behavior of a lactose DPI carrier.

Synthesis of carboxyl-modified rod-like SBA-15 by rapid co-condensation.

Carboxyl-modified SBA-15 rod-like mesoporous materials have been synthesized by a facile rapid co-condensation of tetraethylorthosilicate (TEOS) and 2-cyanoethyltriethoxysilane (CTES), followed by hydrolysis of cyanide groups in sulfuric acid. The concentration of carboxylic groups was varied by changing the silica source ratio of CTES/TEOS from 0.05 to 0.3. X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the uniform ordered mesoporous structure and rod-like morphology of SBA-15 have been preserved even at the high concentration of carboxylic groups employed. Characterization by Fourier transformed infrared spectroscopy (FTIR), solid-state NMR investigation indicated that carboxylic groups have been successfully grafted onto the surface of SBA-15 through siloxane bonds [(O(3))SiCH(2)CH(2)COOH. The negative charges of the modified SBA-15 materials were enhanced by the presence of the carboxylic groups on the surface. The capacity of lysozyme adsorption of the modified SBA-15 materials were found to be significantly improved as compared with pure silica SBA-15. The maximum amount of lysozyme adsorption on carboxyl-modified was increased with the pH of solution increased from 5.5 to 9.0.

Drug release study of large hollow nanoparticulate aggregates carrier particles for pulmonary delivery.

The aim of the present work is to examine the viability of using large hollow nanoparticulate aggregates as the therapeutic carrier particles in dry powder inhaler delivery of nanoparticulate drugs. The large hollow carrier particles are manufactured by spray drying of nanoparticulate suspensions of biocompatible acrylic polymer with loaded drugs. The size and concentration of the nanoparticles, as well as the phospholipids inclusion, have been known to influence the resulting morphology (i.e. size and degree of hollowness) of the spray-dried carrier particles. The effects of the resulting morphology of the carrier particles on the drug release rate are therefore investigated by varying the above three variables. The results of the drug release study are presented using aspirin and salbutamol sulfate as the model drugs with a varying degree of water solubility. The results indicate that the drug release rate is governed by the degree of hollowness of the carrier particles, and to a lesser extent by the nanoparticles size, as a result of the variation in the drug loading capacity of nanoparticles of different sizes.

Influence of particle wall adhesion on particle electrification in mixers.

In this work, particle electrification in the Turbula and horizontally oscillating mixers were investigated for adipic acid, microcrystalline cellulose (MCC), and glycine particles. MCC and glycine particles acquired positive electrostatic charges, while adipic acid particles attained negative charges in both mixers. Adipic acid (of sieved size larger than 500 microm), MCC, and glycine particles were monotonically charged to saturated values, and had negligible wall adhesion. On the contrary, the adipic acid particles, both unsieved and sieved but of smaller sieved size fraction, exhibited very different charging kinetics in the horizontally oscillating mixer. These adipic acid particles firstly acquired charges up to a maximum value, and then the charges slowly reduced to a lower saturated value with increasing mixing time. Furthermore, these particles were found to adhere to the inner wall of the mixer, and the adhesion increased with mixing time. Surface specific charge densities for adipic acid particles were estimated based on particle size distribution, and were found to increase with particle mean diameters under the conditions investigated. The results obtained from the current work suggested that electrostatic force enhanced particle-wall adhesion, and the adhered particles can have a significant impact on particle electrification.