Chitosan Dextran Research Articles

Reproductive Performance of Female Rabbits Inseminated with Extenders Supplemented with GnRH Analogue Entrapped in Chitosan-Based Nanoparticles.

Rabbit is a reflexively ovulating species. Accordingly, in the practice of artificial insemination (AI) ovulation must be induced via exogenous GnRH (Gonadotropin-Releasing Hormone) administration, which may be performed intramuscularly, subcutaneously, or intravaginally. Unfortunately, the bioavailability of the GnRH analogue when added to the extender is lower due to the proteolytic activity in the seminal plasma and the poor permeability of the vaginal mucosa. The aim of the study was to refine the practice of AI practice in rabbits by replacing parenteral GnRH analogue administration (subcutaneous, intravenous, or intramuscular injection) with intravaginal application, while reducing its concentration in the diluent. Extenders containing the buserelin acetate in chitosan-dextran sulphate and chitosan-alginate nanoparticles were designed and 356 females were inseminated. Reproductive performance of females inseminated with the two experimental extenders, receiving 4 μg of buserelin acetate intravaginally per doe, was compared with that in the control group, the does of which were inseminated with the extender without the GnRH analogue and induced to ovulate with 1 μg of buserelin acetate administered intramuscularly. The entrapment efficiency of the chitosan-dextran sulphate complex was higher than that of chitosan-alginate. However, females inseminated with both systems showed similar reproductive performance. We conclude that both nanoencapsulation systems are an efficient way of intravaginal ovulation induction, allowing a reduction in the level of the GnRH analogue normally used in seminal doses from 15-25 μg to 4 μg.

Design of plasticized proton conducting Chitosan:Dextran based biopolymer blend electrolytes for EDLC application: Structural, impedance and electrochemical studies

In this work, for the use of an electrical double-layer capacitor (EDLC) device applications, the fabrication and characterization of solid polymer electrolytes (SPEs) based on chitosan-dextran (CS-DN) blended polymer doped and plasticized with ammonium thiocyanate (NH 4 SCN) and glycerol are studied, respectively. The Fourier transform infrared (FTIR) spectroscopy method has been used to investigate the structural behavior of electrolytes. It was observed that the FTIR bands are shifted and decreased in their intensities with the increased glycerol plasticizer content and it results in the complex formation. According to the electrical impedance spectra (EIS), the electrolyte incorporated with high contents of plasticizer (42 wt%) revealed the highest ionic conductivity of (3.08 × 10 −4 S/cm). The electrical equivalent circuits (EEC) were used to investigate the circuit elements of the electrolytes further. Increasing glycerol plasticizers verified an improvement in ions density number (n), mobility (μ), and diffusion coefficient (D). The transference number measurements (TNM) indicated that the predominant charge carriers in the conduction process are ions where the ( t ion ) is 0.95. According to the linear sweep voltammetry (LSV) study, the uppermost conducting sample was found to have sufficient anode stability with a breakdown voltage of 1.9 V that can be used in electrochemical devices. The absence of peaks in the cyclic voltammetry (CV) demonstrated that the charge storage mechanism within the constructed EDLC is fully capacitive. Based on this finding, the starting specific capacitance ( C s ), energy density ( E d ), and power density ( P d ) have been identified to be 118F/g, 13.2 Wh/kg, and 1560 W/kg, respectively. Throughout its 100 cycles, the equivalence series resistance ESR value was between 53 and 117 Ω.

Imaging Self-Healing Hydrogels and Chemotherapeutics Using CEST MRI at 3 T.

Imaging hydrogel-based local drug delivery to the brain after tumor resection has implications for refining treatments, especially for brain tumors with poor prognosis and high recurrence rate. Here, we developed a series of self-healing chitosan-dextran (CD)-based hydrogels for drug delivery to the brain. These hydrogels are injectable, self-healing, mechanically compatible, and detectable by chemical exchange saturation transfer magnetic resonance imaging (CEST MRI). CD hydrogels have an inherent CEST contrast at 1.1 ppm, which decreases as the stiffness increases. We further examined the rheological properties and CEST contrast of various chemotherapeutic-loaded CD hydrogels, including gemcitabine (Gem), doxorubicin, and procarbazine. Among these formulations, Gem presented the best compatibility with the rheological (G': 215.3 ± 4.5 Pa) and CEST properties of CD hydrogels. More importantly, the Gem-loaded CD hydrogel generated another CEST readout at 2.2 ppm (11.6 ± 0.1%) for monitoring Gem. This enabled independent and simultaneous imaging of the drug and hydrogel integrity using a clinically relevant 3 T MRI scanner. In addition, the Gem-loaded CD hydrogel exhibited a longitudinal antitumor efficacy of Gem over a week in vitro. Furthermore, the CD hydrogel could be visualized by CEST after brain injection with a contrast of 7.38 ± 2.31%. These natural labels on both the chemotherapeutics and hydrogels demonstrate unique image-guided local drug delivery for brain applications.

A Removable Artificial Cell Wall for Withstanding Ciprofloxacin.

The pollution of antibiotics in aquaculture environment is increasingly serious, and excessive antibiotics will kill the probiotics in aquaculture feed. How to improve the viability of probiotics in the antibiotics-contaminated environment is of significance. In this study, a new strategy for protecting Saccharomyces cerevisiae cells in situ against antibiotics is constructed based on cell surface engineering technology by putting on wearable protective layers for cells. The protective layer is constructed around cellular surface via the self-assembly of coacervate microdroplets that consist of carboxymethyl chitosan and carboxyl dextran. Without affecting the cell viability, the protective layer can grasp ciprofloxacin and decrease the contact of ciprofloxacin to cells and consequently improve the survival rate of cells when exposing to ciprofloxacin. This work highlights a facile strategy to establish removable artificial cell wall by biodegradable polysaccharides for improving the productivity of probiotics in antibiotic environments.

Central composite rotatable design for optimization of budesonide-loaded cross-linked chitosan–dextran sulfate nanodispersion: characterization, in vitro diffusion and aerodynamic study

Budesonide is a BCS class II drug with low water solubility (0.045 mg/mL) and low oral bioavailability (6–8%) due to high first pass effect. The aim is to prepare cross-linked chitosan–dextran sulfate nanoparticles and/or nanodispersion. Nebulizable cross-linked nanodispersion was prepared by the solvent evaporation technique and characterized through XRPD, FTIR, mean particle size (MPS), polydispersity index (PDI), zeta potential (ZP), drug loading, entrapment efficiency, SEM, % production yield, in vitro diffusion, aerodynamic and stability study. The optimization of formulation was done by using central composite rotatable design to study the effect of independent variables, concentration of chitosan (X1) and concentration dextran sulfate (X2) on the dependent variables, MPS (Y1), drug loading (Y2) and % CDR (% cumulative drug release) (Y3). The MPS, PDI, and ZP of budesonide-loaded nanoparticles were 160.8 ± 0.27 nm, 0.36 ± 0.04, and 13 ± 0.894 mV, respectively. The percent drug loading of all the batches was found in range of 10–16%. The emitted drug in target region (alveoli) was measured by using HPLC and it was found to be 18.26%. It was found that, nanodispersion had the optimum in vitro aerodynamic behavior. Stability study results showed no significant change in MPS, PDI, ZP, and % CDR after three month storage. In conclusion, cross-linked chitosan–dextran sulfate nanoparticles had properties suitable for nebulizable dispersion of increased drug loading, in vitro drug release and avoiding the first pass effect.

Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan-dextran sulfate nanoparticles enhances their expression and anti-cancer effects.

In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4) expression is downregulated by promoter methylation. In this study, we evaluated the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS-DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex coacervation technique, and particle size ranged from 300nm for empty particles to 337nm for particles containing the proteins. Measurement of the zeta potential showed that all preparations were around 25mV or above, suggesting stable formulation and good affinity for the DNA molecules. The CS-DS nanoparticle formulation maintained high integrity and entrapment efficiency. Gene delivery of SFRP4 and its domains showed enhanced biological effects in both JU77 and ONE58 cell lines when compared to the non-liposomal FUGENE® HD transfection reagent. In comparison to the CRD nanoparticles, both the SFRP4 and NLD nanoparticles significantly reduced the viability of MM cells, with the NLD showing the greatest effect. The CS-DS nanoparticle effects were observed at an earlier time point and with lower DNA concentrations. Morphological changes in MM cells were characterized by the formation of membrane-associated vesicles and green fluorescent protein expression specific to SFRP4 and the NLD. The findings from our proof-of-concept study provide a stepping stone for further investigations using in vivo models.

Chitosan-dextran sulphate nanoparticles for GnRH release in rabbit insemination extenders.

This study was designed to develop chitosan (CS)-dextran sulphate (DS) nanoparticles containing a GnRH analogue and to study their effect on rabbit (Oryctolagus cuniculus) semen quality. Six experimental extenders were tested as follows: (control) Tris-citric acid-glucose (TCG), (1) 0.05% CS-0.05% DS (4:1), (2) 0.1% CS-0.05% DS (4:1), (3) 0.05% CS-0.05% DS (3:1), (4) 0.1% CS-0.05% DS (3:1), (5) 0.1% CS-0.05% DS (2:1). CS and DS were dissolved in TCG medium, and nanoparticles were obtained through magnetic stirring. Rabbit seminal samples were incubated up to 5hr at 37°C in the extenders, and seminal quality was evaluated. The entrapment efficiency was 40%-50%. After 5hr at 37°C, a 20% of the hormone was released. Results showed that the presence of CS-DS nanoparticles did not affect rabbit semen motility, viability and membrane functionality; however, acrosome integrity was significantly higher versus control (p<.001).

Chitosan Dextran gel as an anti adhesion agent in a postlaminectomy spinal sheep model

Introduction: Post-operative peridural adhesions increase morbidity after neurosurgical procedures. Aim of this study is to assess safety and efficacy of Chitosan-Dextran (CD) gel as an anti–adhesion agent in a spinal laminectomy sheep model. Methods: Eighteen sheep were used in this study with 6 animals in each treatment arm (namely, CD gel, Gelfoam paste and normal saline control). Posterior lumbar laminectomy was performed in all animals and the dura was exposed intact. Test agents were applied over the exposed dura and the wound was closed in layers. Sheep were euthanized at the end of three months. MRI spine was performed after euthanasia to assess epidural fibrosis. Adhesion in the spinal specimen was assessed by Peel test and histopathology was used to assess safety of the agents. Results: Average scores for the Peel test for CD gel, Gelfoam and normal saline control groups were 1.16 (95% CI, 0.5–1.7), 1.5 (95% CI, 0.6–2.3) and 3 (95% CI, 2.1–3.8) respectively. There was significant reduction in adhesions between treatment and normal saline treated groups (p=0.0292), with no difference between Gelfoam and CD gel groups (p=0.56). Average scores on MRI for CD gel, Gelfoam and normal saline groups were 1.4 (95% CI, 0.9–1.8), 1.5 (95% CI, 1.2–1.8) and 1.6 (95% CI, 1.3–1.8) respectively, with no significant difference in fibrosis amongst (p=0.2992). Histopathology did not show any adverse effects. Conclusion: CD gel is an effective agent to reduce epidural adhesions with a good safety profile in neural tissue.

The use of chitosan-dextran gel shows anti-inflammatory, antibiofilm, and antiproliferative properties in fibroblast cell culture.

Chitosan-dextran gel has been used as an antihemostatic agent and antiadhesive agent after endoscopic sinus surgery. Because Staphylococcus aureus biofilms have been implicated in recalcitrant chronic rhinosinusitis, this study aimed to further investigate the (i) anti-inflammatory, (ii) bacterial biofilm inhibition, (iii) antiproliferative effects, and (iv) wound-healing properties of chitosan and chitosan-dextran gel. Fibroblasts were isolated from human nasal tissue and were used to determine the effects of chitosan and chitosan-dextran gel on (i) cell proliferation, (ii) wound healing, (iii) inflammation in fibroblast cultures challenged with superantigens S. aureus enterotoxin B (SEB) and toxic shock syndrome toxin (TSST), and (iv) on S. aureus biofilms. Chitosan was highly effective at reducing IL-8 expression after TSST and SEB challenge. Chitosan was also effective at reducing IL-8 expression of nonchallenged fibroblasts showing its anti-inflammatory effects on fibroblasts in a diseased state. Chitosan-dextran gel showed strong antibiofilm properties at 50% (v/v) concentration in vitro. Dextran, on its own, showed antibiofilm properties at 1.25% (w/v) concentration. Chitosan, on its own, reduced proliferation of fibroblasts to 82% of control proliferation and chitosan-dextran gel reduced proliferation of the fibroblasts to 0.04% of control proliferation. Relative to the no treatment controls, chitosan-dextran gel significantly delayed the wound-healing rate over the first 48 hours of the experiment. Chitosan-dextran gel reduced fibroblast proliferation and wound-healing time, showing a possible mechanism of reducing adhesions in the postsurgical period. Chitosan reduced IL-8 levels, showing its anti-inflammatory properties. Chitosan-dextran gel and dextran treatment showed antibiofilm properties in our model.

Controlling the complexation of polysaccharides into multi-functional colloidal assemblies for nanomedicine

The controlled assembly of oppositely charged polysaccharides led to colloids stable in physiological media, capable of encapsulating a molecular drug and of sorbing proteins at their interface. Two types of particles were obtained: both chitosan–dextran sulfate (CS–DS) and chitosan–heparin (CS–HP) stable over 30days in PBS at 25 and 37°C. At gastric pH 1.2, these particles remained stable over 3days, enough for a stomach transit. The structural analysis by small angle X-ray scattering (SAXS) showed that CS–DS surface was semi-rough and chains inside particle exhibited rod-like conformation. Moreover, the particle interfaces could efficiently be functionalized with anti-OVA or anti-α4β7 antibodies, in PBS, with the conservation of the antibody bioactivity over at least 8days. Finally, during the assembly process, a molecular model drug, AMP, could be encapsulated with a loading efficiency up to 72% for CS–DS particles and 66% for CS–HP. All these data establish that the controlled assembly process under equilibrium conditions lead to colloids well suited for the targeted nanodelivery of drugs.

Enhanced viability of probiotic Saccharomyces boulardii encapsulated by layer-by-layer approach in pH responsive chitosan–dextran sulfate polyelectrolytes

Saccharomyces boulardii was encapsulated by layer-by-layer technique (LbL) using oppositely charged polyelectrolytes, chitosan and dextran sulfate to protect from degradation during its gastrointestinal transit. The protective effect of the coating was evaluated by checking viability after subjecting the coated cells to lyophilisation and simulated gastrointestinal conditions. During lyophilization, coated S. boulardii was found to have an enhanced viability of 7.74±2.00 log CFU/100mg (5.62×106±2.12CFU/100mg) and 5.53±1.85 log CFU/100mg (3.46×105±1.73CFU/100mg) for uncoated cells. On sequential treatment with simulated gastric and intestinal juice, the coated cells had a viability of 4.59±1.52 log CFU/100mg (3.8×104±1.52CFU/100mg) while only 1.90±0.80 log CFU/100mg (0.79×102±0.81CFU/100mg) of uncoated cells survived. Confocal studies displayed the selective permeability of the coated cells which plays a significant role in maintaining the integrity and viability of the yeast cells. This clearly indicates that LbL is an efficient protective encapsulation technique and it could be potentially used for improving therapeutic applications of yeast.

Encapsulation and Release of Moxifloxacin Hydrochloride in Chitosan–Dextran Sulphate Microcapsules

In the present work, multilayer microcapsules of size 350 nm were prepared with layer-by-layer assembly of oppositely charged chitosan and dextran sulphate on silica template. The monodisperse silica particles (310 nm) with fine spherical shape were successfully synthesized by Stober's method. Dissolution of silica particles in HF leads to the formation of hollow capsules. The resulting capsules were found to be able to effectively load moxifloxacin hydrochloride in the interior of the capsules under modest conditions without addition of other reagents, as demonstrated by scanning electron microscopy. Parameters affecting loading and release such as pH and initial concentrations were investigated. Release studies were performed in in-vitro mode with a semi-automatic release protocol, with different pH solutions in water and phosphate buffered saline. The size of silica particles was analysed by dynamic light scattering method. Scanning electron microscopy and energy dispersive X-ray spectroscopy measurements proved the surface morphology and purity of the hollow capsules from the core material. The kinetics of drug release mechanism was studied using Peppas and Higuchi models.

Should chitosan and tranexamic acid be combined for improved hemostasis after sinus surgery?

Chitosan, a β-1,4-linked polymer of glucosamine with lesser amounts of N-acetylglucosamine, has well-recognized hemostatic properties. Chitosan is also able to open tight cellular junctions, facilitating paracellular drug transport and delivery. Chitosan, through topical application, facilitates the systemic delivery of analgesic drugs. Theoretically this ability could be used to enhance the local delivery of hemostatic drugs, such as tranexamic acid, improving chitosan’s role as a topical dressing. Individually a chitosan–dextran gel and tranexamic acid have been shown to improve hemostasis after endoscopic sinus surgery. A combination of both should lead to improved hemostasis and better postsurgical outcomes. The use of a chitosan/tranexamic acid dressing could have a wide range of potential beneficial applications in a number of other clinical surgical settings. While the initial main application might be as an improved external hemostatic dressing, it should also be useful on a range of internal surgical wounds.

The efficacy and safety of chitosan dextran gel in a burr hole neurosurgical sheep model

Achieving and maintaining haemostasis is of paramount importance in neurosurgery. Chitosan has been shown in both animal and human models to be significantly effective in haemostasis as well as in reducing adhesion formation. To evaluate the haemostatic potential and to study histopathological changes caused by novel chitosan dextran gel in a neurosurgical sheep model. Ten sheep underwent neurosurgical burr hole procedure. Bleeding control was tested at the level of bone, dura and brain separately with both chitosan gel and Gelfoam paste on separate burr holes. Baseline bleeding was measured at the time of injury using the Boezaart scale, and then every 2 min after the application of each agent until complete haemostasis or 10 min, whichever was earlier. Safety was assessed through MRI scans and histopathological analysis. Mixed modeling showed no statistical difference in time to haemostasis between chitosan gel and Gelfoam paste (means of log-normalized areas under the curve were 1.3688 and 1.3196 respectively) for each burr hole (p = 0.7768). Logistic regression modeling showed that Chitosan significantly decreased the incidence of bleeding beyond the first time point measured after application of the treatment when compared to Gelfoam (OR = 2.7, p = 0.04). Average edema volume (cm(3)) on post-operative MRI was 0.97 for Gelfoam and 1.11 for (p = 0.49) while average histology scores were 2.5 for Gelfoam versus 3.3 for chitosan (p = 0.32). Chitosan dextran gel is an effective haemostatic agent to control bleeding in brain tissue. It is safe and nontoxic to neural tissue.

Synthesis and In-vitro Photodynamic Studies of the Superparamagnetic Chitosan Hydrogel/Chlorin E6 Nanocarriers

The objective of the present study was to develop superparamagnetic chitosan(CS) � dextran sulfate(DS) hydrogels as a intelligent drug system for effective carrying of Chlorin E6(chn E6) photosensitizer to cancer cells. This system can be detectable by magnetic Resonance Imaging technique. The study shows that the lifetime of the triplet state for chn E6 photosensitizer is significantly increase when encapsulate into hydrogel. In addition to the possible enhancement of 1O2 generation, other advantages to incorporating chn E6 -based PS agents into hydrogel include the ability to solubilize these generally hydrophobic agents, the small and uniform size of hydrogels, and potential for passive targeting of solid tumors via the enhanced permeation and retention effect decreasing systemic photosensitization.

Mucoadhesive Chitosan–Dextran Sulfate Nanoparticles for Sustained Drug Delivery to the Ocular Surface

To characterize nanoparticles produced by self-assembly of oppositely charged polymers, cationic chitosan (CS), and anionic dextran sulfate (DS), for drug delivery to the ocular surface. The goal is to overcome the short residence time of topical drugs through their sustained release from mucoadhesive nanoparticles. Chitosan-dextran sulfate nanoparticles (CDNs) were produced by mixing CS and DS; polyethylene glycol-400 was used as a surface stabilizing agent. Fourier transform infrared spectroscopy (FTIR) spectra of CS, DS, and CDNs were determined in the wavenumber range of 4,000-700 cm(-1) to assess the ionic interactions in the formation of CDNs. The physicochemical properties, entrapment efficacy, and dissolution profile of CDNs were investigated using Rhodamine B (RhB) and Nile Red (NR) as drug analogs. The mucoadhesiveness of the CDNs was assessed by imaging the retention of the fluorescein isothiocyanate-labeled CDNs on the cornea ex vivo, which was subjected to shear stress by a steady stream of saline solution. CDNs were obtained by the polyelectrolyte complexation technique. The FTIR spectra of CDNs showed spectral shifts in the amine and sulfate regions, confirming an involvement of electrostatic interactions between cationic CS and anionic DS. The CDNs were spherical in shape and segregated. They possessed a particle size of ~400 nm with a polydispersity index of 0.3 and exhibited a zeta potential of ~40 mV. A high entrapment efficacy of up to 80% was observed with both RhB and NR. In the dissolution experiments, NR was released from CDNs within 60 min, but RhB was not released. This indicates that the release of drugs could depend on their molecular interactions with the particle. Exposure of CDNs to lysozyme, which is found in tears, had no effect on the mean particle size or the surface charge. Instillation of NR, RhB, and FITC in the presence of saline irrigation resulted in their rapid disappearance (<5 min) from the corneal surface. In contrast, fluorescent CDNs showed retention on the cornea even after 60 min. Cationic and biocompatible mucoadhesive CDNs have been developed for sustained drug delivery to the ocular surface. The CDNs were stable to lysozyme and showed prolonged adherence to the corneal surface.

A blinded randomized controlled trial evaluating the efficacy of chitosan gel on ostial stenosis following endoscopic sinus surgery

Stenosis of sinus ostia following endoscopic sinus surgery (ESS) is the most common reason for revision surgery. Chitosan-dextran (CD) gel has been shown to be an effective hemostatic agent; however, its effects on ostial stenosis are unknown. This study aims to quantify the effect of CD gel on circumferential scarring following ESS. A prospective, blinded, randomized, controlled trial was conducted in 26 patients undergoing ESS. Measurements of neo-ostia were taken using a standard-sized measuring probe. CD gel was applied unilaterally, while contralateral sides received no gel. Ostial diameters were measured by a blinded observer at 2, 8, and 12 weeks postoperation. Sinus ostial areas calculated as a proportion of the original were compared for each ostium at each time point. Intraoperative ostial areas were comparable for CD gel and control sides (38 mm(2) vs 39 mm(2) , 131 mm(2) vs 120 mm(2) , and 203 mm(2) vs 193 mm(2) , in frontal, sphenoid, and maxillary ostia, respectively; p > 0.05). CD gel significantly improved sinus ostial patency. The largest difference was seen when ostial areas at 12 weeks were compared with their corresponding baseline areas (66% vs 31% frontal, p < 0.001; 85% vs 47% sphenoid, p < 0.001; and 74% vs 54% maxillary ostia, p = 0.002). The difference between raw ostial areas reached statistical significance in sphenoid (p < 0.001) and maxillary (p = 0.01), but not in frontal ostia (p > 0.05) at 12 weeks. CD gel produced significantly less stenosis of all neo-ostia following ESS and may reduce the necessity for revision surgery in patients with chronic rhinosinusitis.

Microencapsulated chitosan–dextran sulfate nanoparticles for controled delivery of bioactive molecules and cells in bone regeneration

This research work aimed to synthesize and characterize a novel dual delivery system comprised of BSA-loaded in chitosan–dextran sulfate nanoparticulated carriers and mesenchymal stem cells that are encapsulated into alginate microparticles. The physicochemical and biological characteristics of this novel system, such as, morphology, release, swelling, and cytotoxicity were thoroughly characterized. The results obtained from confocal microscopy demonstrate that chitosan–dextran sulfate nanoparticles and cells are fully encapsulated within alginate microparticles, and spatially dispersed in the microparticle matrix. Moreover, scanning electron microscopy images revealed that these micro-sized carriers possess a rough surface, an important parameter that also promoted proper cell migration and adhesion. Notably, the incorporation of BSA in this duplex nano-micro delivery system extended its release profile throughout time, in comparison with microparticles alone, whilst not eliciting any cell damage. Taken together, these findings suggest that this dual carrier is a versatile delivery system with potential for a spatiotemporally controlled release of bioactive molecules and cells.

Preliminary studies on the development of IgA-loaded chitosan–dextran sulphate nanoparticles as a potential nasal delivery system for protein antigens

This study describes the development of a biodegradable nanoparticulate system for the intranasal delivery of multiple proteins. Chitosan (CS)–dextran sulphate (DS) nanoparticles were developed and optimised for the incorporation of pertussis toxin (PTX) and a potential targeting ligand (immunoglobulin-A, IgA). In vitro characterization and in vivo uptake studies were performed for the evaluation of developed nanoparticles. The ratio of CS to DS, the order of mixing and pH of nanoparticle suspension were identified as important formulation factors governing the size and zeta potential of nanoparticles. An optimised CS–DS nanoparticle formulation prepared with the CS to DS weight ratio of 3 : 1 was used to load PTX and/or IgA. Entrapment efficiency of >90% was obtained for both. The in vivo uptake of IgA-loaded CS–DS nanoparticles in mice showed a preferential uptake of nanoparticles probably by nasal membranous or microfold cells following intranasal administration. The results of this study indicate the potential application of IgA-loaded CS–DS nanoparticles as a nasal vaccine delivery system.

Enhanced Immune Response Against Pertussis Toxoid by IgA-Loaded Chitosan–Dextran Sulfate Nanoparticles

The objective of the present study was to evaluate immunological activities of chitosan-dextran sulfate (CS-DS) nanoparticle formulation of pertussis toxoid (PTXd) and its combination with a potential immunological adjuvant, immunoglobulin A (IgA). CS-DS nanoparticles were prepared using a complex coacervation (polyelectrolyte complexation) technique. CS-DS nanoparticle formulations with size and zeta potential in a range of 300-350 nm and +40-+55 mV, respectively, were obtained. An entrapment efficiency of more than 90% was obtained for pertussis toxin and IgA in CS-DS nanoparticles. All loaded nanoparticle formulations showed less than 20% of release within 24 h in in vitro release studies. The immunological evaluation of developed formulations in female Balb/c mice groups showed that the CS-DS nanoparticles formulations induced significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with conventional alum-adjuvanted PTXd formulation administered by subcutaneous route. This study indicated the potential of CS-DS nanoparticles to be a simple and effective particulate delivery system with in-built immunological adjuvant property for acellular protein antigens. The study also revealed the potential important role of IgA-loaded CS-DS nanoparticles as a novel immunological adjuvant for vaccine delivery.