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Effective postoperative therapy is crucial for preventing tumor recurrence and metastasis. Nanocomposite (NC) pastes of Gel/CS-g-CD NP with unique viscoelastic properties and pH-responsive drug delivery ability were prepared from gelatin (Gel) and β-cyclodextrin-grafted chitosan nanoparticles (CS-g-CD NPs) through host–guest interactions between the aromatic amino acid residues of gelatin and β-cyclodextrin. The dynamic rheological properties, shear strength, and shear viscosity were modulated through variations in the concentration of CS-g-CD NPs in the NC pastes. Due to the reversibility of the host–guest interactions, the NC pastes exhibited shear-thinning and self-healing properties, endowing them with good injectability. Loading of doxorubicin (DOX) in the nanoparticles (DOX-CSCD NPs) forming the NC pastes of Gel/DOX-CSCD NP allowed pH-triggered DOX release in a simulated tumoral microenvironment, because of the labile nature of the CS-g-CD NPs under acidic conditions. In vitro experiments showed that the NC pastes of Gel/DOX-CSCD NP induced sustained tumor cell inhibition. Moreover, in vivo studies with tumor-bearing mice indicated that the NC pastes of Gel/DOX-CSCD NP can effectively inhibit tumor recurrence after surgical resection. Therefore, the NC pastes described in this work may act as an effective injectable drug delivery system for postoperative tumoral treatment.
This work prepared food-grade oleogel-based Pickering emulsion stabilized by ovotransferrin (OVT)–carboxymethyl chitosan (CMCS) nanoparticles (OPEOC). The analysis of emulsified phase volumes and stability index exhibited that OPEOC with different volumes of oil fraction remained stable for 2 months of storage. The prepared Pickering emulsions were used as delivery systems for curcumin. In vitro digestive studies showed that OPEOC significantly improved the degree of lipolysis and the bioaccessibility of curcumin compared to the sunflower seed oil-based oleogel. The oleogel-based Pickering emulsions fabricated in the present study had noticeable storage stability, high loading and improved bioaccessibility of nutraceuticals, which might provide new insights into the development of novel food-grade Pickering emulsions with excellent properties.
Oral administration of insulin faces multiple biological challenges, such as varied digestive environments, mucin exclusion, and low epithelial cells’ absorption. In the present study, a hyaluronic acid (HA)-coated chitosan (CS) nanoparticle (HCP) delivery system is fabricated for insulin oral delivery. It is hypothesized that the developed nanoparticles will protect insulin from digestive degradation, promote intestinal epithelial cell absorption, and exert strong in vivo hyperglycemic ability. Nanoparticles formulated by CS and sodium tripolyphosphate (TPP) are optimized to form the core nanoparticles (CNPs). HA is further applied to coat CNP (HCP) to improve stability, reduce enzymatic degradation, and promote absorption of insulin. HCP promotes insulin uptake by Caco-2 cells, absorbs less mucin, and improves intestinal absorption. Moreover, an in vivo test demonstrates that oral administration of insulin-loaded HCP exerts strong and continuous hyperthermia effect (with a pharmacological availability (PA) of 13.8%). In summary, HCP is a promising delivery platform for insulin oral administration in terms of protecting insulin during digestion, facilitating its absorption and ultimately promoting its oral bioavailability.
Hypothermic machine perfusion (HMP) is a preferable measure to preserve kidneys from donation after cardiac death (DCD), while the current standard perfusate is imperfect. We synthesized amphiphilic chitosan, N-alkylated-O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (N-alkyl-O-HTCC) as additive in the perfusate, which can self-assembly into micelles in water (size 133 ± 8.48 nm) (ζ-potential 43.9 ± 2.06 mV), with good antibacterial activity for Escherichia coli and Staphylococcus aureus . The derivates can also deliver hydrophobic drug Alda-1 into kidneys through HMP, with drug loading ratio (~42.14%). The delivery system specifically activated mitochondrial acetaldehyde dehydrogenase 2 in kidneys and reduced the ischemic injury. What's more, the addition of N-alkyl-O-HTCC in HMP also activated mitochondria superoxide dismutase 2, presented nice antioxidant activity . These all helped to improve the quality of DCD kidneys. This study provides a feasible amphiphilic carrier for hydrophobic drugs, and provides efficient guidance for perfusate improvement.
In this work, lignin/chitosan nanoparticles (Lig/Chi NPs) with controlled structures were synthesized in a simple and scalable microfluidic system. When the positively charged chitosan and the negatively charged lignin solution were blended in a microreactor, Lig/Chi NPs were rapidly formed via the electrostatic coassembly between the amino groups of chitosan and the carboxyl groups of lignin. The ζ potential changes from negative (−13 mV) to positive (+54.5 mV) for Lig NPs and Lig/Chi NPs, respectively. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results demonstrated that Lig/Chi NPs have an average particle size of about 180 nm, which can be used as nanocarriers for drug delivery. The anticancer drug nanoparticles with docetaxel (DTX) and curcumin (CCM) were prepared by coassembly with Lig/Chi NPs in a microreactor, which had good drug loading efficiency, biocompatibility, and can release drugs in response to pH in the weakly acidic environment of the tumor. The drug release amounts in acidic solutions that simulated the tumor microenvironment were 51% (DTX@Lig/Chi NPs) and 50% (CCM@Lig/Chi NPs), respectively, which were better than the release amounts at pH 7.4, and have an obvious killing effect on HeLa cells.
In order to reveal the relationship between the degree of crosslinking and the properties of chitosan nanoparticles, a potassium polyvinyl sulfate (PVSK) titration method was established for the determination of free amino group in chitosan, which showed that there was a window effect in the crosslinking degree and particle size of three kinds of molecular weight chitosan cross-linked by different content of tripolyphosphate (TPP), and the nanoparticles with moderate crosslinking degree were smaller. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) showed the moderate degree of cross-linking nanoparticles had strong antibacterial properties. IR analysis showed that the interaction between chitosan nanoparticles with different crosslinking degree and TPP were different. X-ray diffraction analysis showed that the cross-linked chitosan nanoparticles were amorphous. Above all, the crosslinking degree of TPP cross-linked chitosan nanoparticles was related to the particle size and antibacterial properties.
Osteoarthritis (OA) caused by the articular cartilage degeneration is closely related to the lubrication dysfunction of joint . At present, injecting biolubricants into the joint cavity is regarded as an effective strategy for the treatment of arthritis. Herein, a biocompatible chitosan (CS)-based nanoparticles (NPs) biolubricant ( [email protected] NPs) with dual function of lubrication and anti-inflammatory was fabricated. Zwitterionic polyelectrolyte brush poly(2-methacryloyloxyethyl phosphorylcholine, PMPC) was grafted onto the NPs via atom transfer radical polymerization (ATRP) strategy, while the anti-inflammatory drug (diclofenac sodium, DS) was encapsulated within them. Under the synergistic effect rolling lubrication and hydration lubrication mechanisms, the obtained biolubricant exhibited superior lubrication performance in either artificial joint materials or cartilage contacts, which presents great potential for OA treatment.
We developed magnetic chitosan nanoparticles (CS‑Fe 3 O 4 ) with mean diameter of 15–20 nm. Subsequently, these inorganic-organic composite nanoparticles were modified using an imidazole-based functional ionic liquid (IL). The prepared support (IL‑CS‑Fe 3 O 4 ), which was used to immobilize porcine pancreatic lipase (PPL), was characterized using Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Circular dichroism (CD) was used to analyze the secondary structure of immobilized PPL. The immobilized PPL (PPL‑IL‑CS‑Fe 3 O 4 ) exhibited 1.93-fold higher specific activity than PPL‑CS-Fe 3 O 4 when triacetin was used as the substrate, and showed 95 mg/g of lipase immobilization capacity and 382% of activity recovery. The residual activity of PPL‑IL‑CS‑Fe 3 O 4 was above 60% of the initial activity after incubation at 50 °C for 6 h, as was higher than that of PPL‑CS‑Fe 3 O 4 which showed 40% of the initial activity. In addition, PPL‑IL‑CS‑Fe 3 O 4 retained 84.6% of the initial activity after 10 cycles, whereas PPL‑CS‑Fe 3 O 4 retained only 75.5% activity. Furthermore, the kinetic parameters, apparent K m and V max of PPL‑IL‑CS‑Fe 3 O 4 were 2.51 mg/mL and 1.395 U/mg respectively, these results indicated that the immobilized PPL had better affinity towards the substrate, especially when the nanoparticles were modified by functional IL. Besides, the magnetic chitosan nanoparticles loaded with PPL were easily recovered. A novel, efficient, and practical method for enzyme immobilization was developed.
Nano-embedding has appeared as a feasible technology to improve the high-quality utilization of royal jelly (RJ). Therefore, the ionic gelation method was proposed to prepared chitosan nanoparticles loaded with royal jelly (RJNPs) and the characterization and biological activity of RJNPs were evaluated in this study. Fourier-transform infrared spectroscopy, differential scanning calorimetry and x-ray diffraction results showed that the methyl and methylene groups of royal jelly combine with the amino groups of chitosan (CS) to become an amorphous polymer. In addition, the 48.68 % encapsulation efficiency and 31.90 % loading capacity were obtained under the optimal ratio of 1:1 RJ to CS, and the average particle size was <80 nm. The antioxidant activity of RJNPs gradually increased with the increase of the RJ proportion. Interestingly, the antibacterial activity on gram-positive bacteria was better than gram-negative bacteria. Most important, RJNPs exhibited better stability and digestibility rather than single RJ. Overall, these findings indicated that RJ can be embedded in chitosan, and RJNPs exhibited good thermal stability, antioxidant activity, antibacterial activities and bioavailability, which was important for the development and application of the high-quality utilization of RJ.
The adsorption characteristics of hydroquinol from aqueous solutions onto the β-cyclodextrin modified magnetic chitosan nanoparticles (CMCN) had been investigated. The characteristics results of FTIR , SEM and XRD showed that CMCN was successfully prepared. The influences of the pH of the solution and the contact time on the adsorption amounts had been discussed, and the appropriate process conditions for the adsorption of hydroquinol had been obtained. Equilibrium experiments fitted well with the Freundlich isotherm model, and the maximum adsorption capacity of the CMCN at 303 K was determined to be 1.75 mmol/g for hydroquinol at the concentration of 9.0 mmol/L, much higher than some conventional adsorbents. The CMCN was stable and easily recovered. Moreover, the adsorption capacity was about 90% of the initial saturation adsorption capacity after being used four times.
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