Trimethyl Chitosan Research Articles

Oral Delivery of Insulin from Trimethyl Chitosan/Tragacanth: In Vitro, MTT, and In Vivo Bioactivity Tests

: Insulin-loaded Trimethyl Chitosan (TMC)/tragacanth microspheres were prepared by microemulsion dispersion and triggered in situ gelation. Microspheres were characterized by their mean size and distribution by laser diffraction spectroscopy and Brunauer-Emmet-Teller theory. Insulin encapsulation efficiency and in vitro release were determined by Bradford protein assay, and bioactivity was assessed in vitro using an enzyme-linked immunoassay diagnostic kit and in vivo using Wistar diabetic rats. TMC/tragacanth particles suppressed insulin release in acidic media and promoted a sustained release at near-neutral conditions. Micro-capsulated insulin was bioactive, demonstrated by both in vivo and in vitro bioassays.

Tigecycline Absorption Improved by Selected Excipients.

To investigate the effects of (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), tocopherol polyethylene glycol 1000 succinate (TPGS), sodium desoxycholate (SDOCH), trimethyl chitosan (TMC), and sodium caprate (C10) on the plasma concentration and the oral bioavailability of tigecycline in broiler chickens. To test the effects of the excipients on absorption of tigecycline, a tetracycline that is poorly absorbed from the gastrointestinal tract, broiler chickens were used as an animal model. Tigecycline (10 mg/kg body weight) was administered intravenously, orally, and orally with one of the excipients. Plasma samples were taken after administration. To measure tigecycline concentrations, high-performance liquid chromatography coupled with tandem mass spectrometry was used. Compartmental and non-compartmental analyses were used for pharmacokinetic analyses of mean plasma concentrations versus time. With the exception of sodium caprate, all the excipients significantly increased the area under the curve and bioavailability of tigecycline (p < 0.05). These parameters were approximately doubled by HP-β-CD, TPGS, and SDOCH, with 95% confidence intervals (95% CIs) for the difference that included only increases of 1.5-fold or higher (bioavailability: control, 1.67%; HP-β-CD, 3.24%; TPGS, 3.30%; and SDOCH, 3.24%). The increases in these parameters were smaller with DM-β-CD and TMC (DM-β-CD, 2.41%; TMC, 2.55%), and the 95% CIs ranged from close to no difference to nearly double the values in the control group. These results indicate that HP-β-CD, TPGS, and SDOCH substantially increase the area under the curve and oral bioavailability of tigecycline. They suggest that DM-β-CD and TMC may also substantially increase these parameters, but more research is needed for more precise estimates of their effects.

Magnetically controlled drug delivery and hyperthermia effects of core-shell Cu@Mn3O4 nanoparticles towards cancer cells in vitro

Recent increase in the integration of nanotechnology and nanosciences to the biomedical sector fetches the human wellness through the development of sustainable treatment methodologies for cancerous tumors at all stages of their initiation and progression. This involves the development of multifunctional theranostic probes that effectively support for the early cancer diagnosis, avoiding non-target cell toxicity, controlled and customized anticancer drug release etc. Therefore, to advance the field of nanotechnology-based sustainable cancer treatment, we fabricated and tested the efficacy of anticancer drug-loaded magnetic hybrid nanoparticles (NPs) towards in vitro cell culture systems. The developed conjugate of NPs was incorporated with the functions of both controlled drug delivery and heat-releasing ability using Mn3O4 (manganese oxide) magnetic core with Cu shell encapsulated within trimethyl chitosan (TMC) biopolymer. On characterization, the Cu@Mn3O4-TMC NPs were confirmed to have an approximate size of 130 nm with full agglomeration (as observed by the HRTEM) and crystal size of 92.95 ± 18.38 nm with tetragonal hausmannite phase for Mn3O4 spinel structure (XRD). Also, the UV–Vis and FTIR analysis provided the qualitative and quantitative effects of 5-fluororacil (5-Fu) anticancer drug loading (max 68 %) onto the Cu@Mn3O4-TMC NPs. The DLS analysis indicated for the occurrence of no significant changes to the particle size (around 100 nm) of Cu@Mn3O4-TMC due to the solution dispersion thereby confirming for the aqueous stability of developed NPs. In addition, the magnetization values of Cu@Mn3O4-TMC NPs were measured to be 34 emu/g and a blocking temperature of 42 K. Further tests of magnetic hyperthermia by the Cu@Mn3O4-TMC/5-Fu NPs provided that the heat-releasing capacity (% ΔT at 15 min) increases with that of increased frequency, i.e. 28 % (440 Hz) > 22.6 % (240 Hz) > 18 % (44 Hz), and the highest specific power loss (SPL) value observed to be 488 W/g for water. Moreover, the 5-Fu drug release studies indicate that the release is high at a pH of 5.2 and almost all the loaded drug is getting delivered under the influence of the external magnetic field (430 Hz) due to the influence of both Brownian-rotation and Néel relaxation heat-mediated mechanism. The pharmacokinetic drug release studies have suggested for the occurrence of more than one model, i.e. First-order, Higuchi (diffusion), and Korsemeyer–Peppas (non-Fickian), in addition to hyperthermia. Finally, the in vitro cell culture systems (MCF-7 cancer and MCF-10 non-cancer) helped to differentiate the physiological changes due to the effects of hyperthermia and 5-Fu drug individually and as a combination of both. The observed differences of cell viability losses among both cell types are measured and discussed with the expression of heat shock proteins (HSPs) by the MCF-10 cells as against the MCF-7 cancer cells. We believe that the results generated in this project can be helpful for the designing of new cancer therapeutic models with nominal adverse effects on healthy normal cells and thus paving a way for the treatment of cancer and other deadly diseases in a sustainable manner.

Biodegradable trimethyl chitosan nanofiber mats by electrospinning as bioabsorbable dressings for wound closure and healing

The paper aimed to prepare quaternary chitosan-based nanofibers as bioabsorbable wound dressings. To this aim, fully biodegradable chitosan/N,N,N-trimethyl chitosan (TMC) nanofibers were designed and prepared via electrospinning, using poly(ethylene glycol) as sacrificial additive. The new biomaterials were structurally and morphologically characterized by FTIR and NMR spectroscopy, thermogravimetric analysis, X-ray diffraction and scanning electron microscopy, and their properties required for wound dressings application were investigated and discussed in detail. Thus, the nanofiber behavior was investigated by swelling, dynamic vapor sorption, and in vitro biodegradation in media mimicking the wound exudate. The mechanical properties were analysed from the stress-strain curves, the bioadhesivity from the texture analysis and the mucoadhesivity from the Zeta potential and transmittance measurements. The antimicrobial activity was assessed against S. aureus and E. coli strains, and the biocompatibility was tested in vitro on normal human dermal fibroblasts, and in vivo on rats. The application of the fiber mats with the best balance of properties as dressings on deep burn wound models in rats showed wound closure and active healing, with fully restoration of epithelia. It was concluded that the combination of chitosan with TMC into nanofibers provides new potential bioabsorbable wound dressing, opening new perspectives in regenerative medicine.

Biosorption of Escherichia coli Using ZnO-Trimethyl Chitosan Nanocomposite Hydrogel Formed by the Green Synthesis Route.

In this study, we tested the biosorption capacity of trimethyl chitosan (TMC)-ZnO nanocomposite (NC) for the adsorptive removal of Escherichia coli (E. coli) in aqueous suspension. For the formation of ZnO NPs, we followed the green synthesis route involving Terminalia mantaly (TM) aqueous leaf extract as a reducing agent, and the formed ZnO particles were surface-coated with TMC biopolymer. On testing of the physicochemical characteristics, the TM@ZnO/TMC (NC) hydrogel showed a random spherical morphology with an average size of 31.8 ± 2.6 nm and a crystal size of 28.0 ± 7.7 nm. The zeta potential of the composite was measured to be 23.5 mV with a BET surface area of 3.01 m2 g-1. The spectral profiles of TM@ZnO/TMC NC hydrogel on interaction with Escherichia coli (E. coli) revealed some conformational changes to the functional groups assigned to the stretching vibrations of N-H, C-O-C, C-O ring, and C=O bonds. The adsorption kinetics of TM@ZnO/TMC NC hydrogel revealed the pseudo-second-order as the best fit mechanism for the E. coli biosorption. The surface homogeneity and monolayer adsorption of the TM@ZnO/TMC NC hydrogel reflects majorly the entire adsorption mechanism, observed to display the highest correlation for Jovanovic, Redlich-Peterson, and Langmuir's isotherm models. Further, with the use of TM@ZnO/TMC NC hydrogel, we measured the highest adsorption capacity of E. coli to be 4.90 × 10 mg g-1, where an in-depth mechanistic pathway was proposed by making use of the FTIR analysis.

Engineering the Intestinal Lymphatic Transport of Oral Nanoparticles to Educate Macrophages for Cancer Combined Immunotherapy.

The effectiveness of the commonly used therapy is low for treating triple-negative breast cancer (TNBC). Macrophages, accounting for up to 50% of the TNBC tumor mass, are involved in innate and adaptive immunity, which can serve as an effective weapon against TNBC via combined immunotherapy. Here, we engineered mannose and glycocholic acid-modified trimethyl chitosan (MTG) nanoparticles (NPs) encapsulating signal regulatory protein α (SIRPα) siRNA (siSIRPα, a macrophage checkpoint inhibitor) and mucin 1 (MUC1) pDNA (pMUC1, a therapeutic pDNA vaccine) (MTG/siSIRPα/pMUC1 NPs) for in situ educating macrophages via an oral route to exert the cooperative antitumor effects of siSIRPα and pMUC1. Orally delivered MTG-based NPs accumulated in the macrophages in lymph nodes and tumor tissues via the intestinal lymphatic transport pathway, leading to strong cellular immunity responses. Following the transfection of orally administered MTG/siSIRPα/pMUC1 NPs within the same macrophages, siSIRPα strengthened the pMUC1 vaccine-induced systemic cellular immunity, while pMUC1 enhanced siSIRPα-mediated macrophage phagocytosis, M1-phenotype polarization, and tumor microenvironment (TME) remodeling at the tumor sites, thereby inhibiting the growth and metastasis of TNBC. The simultaneous achievements of the mutual promotion of innate and adaptive immunity in the local TME and in the whole body suggested that MTG/siSIRPα/pMUC1 NPs would provide a promising paradigm for the combined immunotherapy of TNBC via oral delivery of genes.

Preparation and characterization of gelatin active packaging film loaded with eugenol nanoparticles and its application in chicken preservation

Edible film combined with nanotechnology is one of the strategies of food intelligent packaging to extend food shelf life. Herein, eugenol-loaded sodium caseinate and trimethyl chitosan composite nanoparticles (ESTNPs) were firstly prepared to improve bioavailability and stability. Subsequently, gelatin films loaded with ESTNPs were fabricated, and microscopic results showed good biocompatibility between nanoparticles and gelatin. The incorporation of ESTNPs significantly improved the light/water/oxygen barrier properties and thermal stability of the film (p < 0.05), while it weakened the mechanical performance. ESTNPs endowed the film with excellent antibacterial efficiency (exceeded 99.99%) and enhanced its antioxidant activity. The ESTNPs/gelatin composite film exhibited good storage stability. The release behavior of eugenol from the film indicated that the composite film was more suitable for acidic foods, which could be used for meat packaging. Results in the antibacterial and preservation tests on chicken breast meat confirmed that the composite film could indeed serve as an active food packaging film for extending the shelf life of the meat without side-effect on the chroma, texture and sense quality. Hence, the prepared edible film combined with ESTNPs has great potential in extending food shelf life and provide a strategy for the preparation of active packaging.

Preparation and Characterization of Trimethyl Chitosan /Hyaluronic Acid Composite Encapsulated with LL37 to Promote Wound Healing in an Animal Model

Preparation and Characterization of Trimethyl Chitosan /Hyaluronic Acid Composite Encapsulated with LL37 to Promote Wound Healing in an Animal Model

The Osteogenic Properties of Calcium Phosphate Cement Doped with Synthetic Materials: A Structured Narrative Review of Preclinical Evidence.

Bone grafting is commonly used as a treatment to repair bone defects. However, its use is challenged by the presence of medical conditions that weaken the bone, like osteoporosis. Calcium phosphate cement (CPC) is used to restore bone defects, and it is commonly available as a bioabsorbable cement paste. However, its use in clinical settings is limited by inadequate mechanical strength, inferior anti-washout characteristics, and poor osteogenic activity. There have been attempts to overcome these shortcomings by adding various natural or synthetic materials as enhancers to CPC. This review summarises the current evidence on the physical, mechanical, and biological properties of CPC after doping with synthetic materials. The incorporation of CPC with polymers, biomimetic materials, chemical elements/compounds, and combination with two or more synthetic materials showed improvement in biocompatibility, bioactivity, anti-washout properties, and mechanical strength. However, the mechanical property of CPC doped with trimethyl chitosan or strontium was decreased. In conclusion, doping of synthetic materials enhances the osteogenic features of pure CPC. The positive findings from in vitro and in vivo studies await further validation on the efficacy of these reinforced CPC composites in clinical settings.

Chitosan Derivatives as Carriers for Drug Delivery and Biomedical Applications.

Over the past few decades, chitosan (CS) has gained the attention of researchers investigating newer biomaterial-based carriers for drugs in pharmaceutical and biomedical research. Combined with its nontoxic behavior, biodegradability, and biocompatibility, chitosan has found widespread applications in the fields of drug delivery, tissue engineering, and cosmetics. As a novel drug carrier, chitosan is regarded as one of the promising biomaterials in the pharmaceutical industry. The extensive use of this cationic biopolysaccharide in the delivery of therapeutic agents has brought a few limitations of chitosan into the limelight. Various chemical modifications of chitosan can minimize these limitations and improve the efficacy of chitosan as a drug carrier. The effectiveness of several chemically modified chitosan derivatives, including trimethyl chitosan, thiolated chitosan, PEGylated chitosan, and other chitosan derivatives, has been investigated by many researchers for the controlled and target specific delivery of therapeutics. The chemically modified chitosan derivatives exhibited greater importance in the current scenario on drug delivery due to their solubility in wide range of media along with their interaction with pharmaceutically active ingredients. Chitosan derivatives have also attracted attention in several biomedical fields, including wound healing, hyperthermia therapy, tissue engineering, and bioadhesives. The present review narrates the sources and common physicochemical properties of chitosan, including several important synthetic modifications to obtain chemically modified chitosans and their applications in target-specific drug delivery, along with several biomedical applications.

Liposome-trimethyl chitosan nanoparticles codeliver insulin and siVEGF to treat corneal alkali burns by inhibiting ferroptosis.

Alkali burns are potentially blinding corneal injuries. Due to the lack of available effective therapies, the prognosis is poor. Thus, effective treatment methods for corneal alkali burns are urgently needed. Codelivery nanoparticles (NPs) with characteristics such as high bioavailability and few side effects have been considered effective therapeutic agents for ocular diseases. In this study, we designed a new combination therapy using liposomes and trimethyl chitosan (TMC) for the codelivery of insulin (INS) and vascular endothelial growth factor small interfering RNA (siVEGF) to treat alkali-burned corneas. We describe the preparation and characterization of siVEGF-TMC-INS-liposome (siVEGF-TIL), drug release characteristics, intraocular tracing, pharmacodynamics, and biosafety. We found that siVEGF-TIL could inhibit oxidative stress, inflammation, and the expression of VEGF in vitro and effectively maintained corneal transparency, accelerated epithelialization, and inhibited corneal neovascularization (CNV) in vivo. Morever, we found that the therapeutic mechanism of siVEGF-TIL is possibly relevant to the inhibition of the ferroptosis signaling pathway by metabolomic analysis. In general, siVEGF-TIL NPs could be a safe and effective therapy for corneal alkali burn.

Synthesis of Trimethyl Chitosan Nanoparticles Containing Recombinant BLF1-stxB Protein of Burkholderia Pseudomallei and Evaluation of its Immunogenicity in Mice

Synthesis of Trimethyl Chitosan Nanoparticles Containing Recombinant BLF1-stxB Protein of Burkholderia Pseudomallei and Evaluation of its Immunogenicity in Mice

The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines.

Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development.

Confinement of Triple-Enzyme-Involved Antioxidant Cascade in Two-Dimensional Nanostructure.

Application of antioxidant enzymes in medical or industrial processes is limited due to their high sensitivity to environmental conditions. Incorporation of such enzymes in nanostructures provides a promising route to obtain highly efficient and robust biocatalytic system to scavenge reactive oxygen species (ROS). Here, this question was addressed by confinement of superoxide dismutase (SOD), horseradish peroxidase (HRP), and catalase (CAT) enzymes into nanostructures containing polyelectrolyte building blocks (alginate (Alg) and trimethyl chitosan (TMC)) and delaminated layered double hydroxide (dLDH) nanoparticle support. The nanocomposite possessed excellent structural and colloidal stability, while antioxidant tests revealed that the enzymes remained active upon immobilization and the developed composite greatly reduced intracellular oxidative stress in two-dimensional cell cultures. Moreover, it effectively prevented hydrogen peroxide-induced double stranded DNA breaks, which is a common consequence of oxidative stress. The results provide important tools to design complex nanostructures with multienzymatic antioxidant activities for ROS scavenging.

Compressed Hydrogen-Induced Synthesis of Quaternary Trimethyl Chitosan-Silver Nanoparticles with Dual Antibacterial and Antifungal Activities.

Quaternary Trimethyl Chitosan (QTMC) and QTMC-Silver Nanoparticles (QTMC-AgNPs) have been synthesized, characterized, and tested as antibacterial agents against Staphylococcus aureus, Escherichia coli, and two plant fungi (Sclerotium rolfsil and Fusarium oxysporum). The as-prepared water-soluble QTMC was in situ reacted with silver nitrate in the presence of clean compressed hydrogen gas (3 bar) as a reducing agent to produce QTMC-AgNPs. UV-vis, ATR-FTIR, HR-TEM/SEM, XPS, DLS, XRD, and TGA/DTG were employed to assess the optical response, morphology/size, surface chemistry, particle size distribution, crystal nature, and thermal stability of the synthesized QTMC-AgNPs, respectively. The as-prepared QTMC-AgNPs were quasi-spherical in shape with an average particle size of 12.5 nm, as determined by ImageJ software utilizing HR-TEM images and further validated by DLS analysis. The development of crystalline nanoparticles was confirmed by the presence of distinct and consistent lattice fringes with an approximate interplanar d-spacing of 2.04 nm in QTMC-AgNPs. The QTMC-AgNPs exhibited significant antibacterial activity with a clear zone of inhibition of 30 mm and 26 mm around the disks against E. coli and S. aureus, respectively. In addition, QTMC-AgNPs showed highly efficient antifungal activity with 100% and 76.67% growth inhibition against two plant pathogens, S. rolfsii and F. oxysporum, respectively, whereas QTMC revealed no impact. Overall, QTMC-AgNPs showed a promising therapeutic potential and,thus, can be considered for drug design rationale.

A Promising Use of Trimethyl Chitosan for Removing Microcystis aeruginosa in Water Treatment Processes.

The increase in cyanobacterial blooms linked to climate change and the eutrophication of water bodies is a global concern. The harmful cyanobacterium Microcystis aeruginosa is one of the most common bloom-forming species whose removal from fresh water and, in particular, from that used for water treatment processes, remains a crucial goal. Different biodegradable and environmentally friendly coagulants/flocculants have been assayed, with chitosan showing a very good performance. However, chitosan in its original form is of limited applicability since it is only soluble in acid solution. The objective of this work was therefore to test the coagulant/flocculant capacity of trimethylchitosan (TMC), a chitosan derivative produced from residues of the fishing industry. TMC has a constitutively net positive charge enabling it to remain in solution regardless of the pH. Results show that even at alkaline pHs, common during cyanobacterial blooms, TMC is effective in removing buoyant cyanobacteria from the water column, both in test tube and Jar-Test experiments. Cell integrity was confirmed by fluorescent stain and electron microscopy. Our findings lead us to conclude that the use of TMC to remove bloom cells early in the treatment of drinking water is both feasible and promising.

Combined inhibition of EZH2 and CD73 molecules by folic acid-conjugated SPION-TMC nanocarriers loaded with siRNA molecules prevents TNBC progression and restores anti-tumor responses

BackgroundAbnormal function or overexpression of CD73 and EZH2 within the tumor microenvironment and tumor cells enhances tumor growth and progression, and in many cases, causes drug resistance. Hence, it seems that silencing the expression of CD73 and EZH2 molecules in breast cancer reduces cancer development and enhances anti-tumor immune responses. Methodswe used siRNA-loaded superparamagnetic iron oxide (SPIONs) nanoparticles (NPs) coated with trimethyl chitosan (TMC) and functionalized with folic acid for co-delivery of EZH2/CD73 siRNAs to 4 T1 murine cancer cells both in vitro and in vivo. ResultsCombination therapy markedly inhibited cancer cells' proliferation, migration, and viability and induced apoptosis in vitro. Moreover, in vivo administration of this combination therapy promoted tumor regression and induced anti-tumor immune responses. DiscussionThe findings indicated the CD73/EZH2 factors inhibition by SPION-TMC-FA NPs as a promising therapeutic strategy in breast cancer treatment.

PREPARATION AND EVALUATION OF TMC LOADED VORICONAZOLE NANOPARTICLES

Objective: Ocular diseases affect a growing number of people across the globe. Hence, the present research work focused to prepare and evaluate voriconazole (VCZ) nanoparticles containing trimethyl chitosan (TMC) for ophthalmic drug delivery with primary goal is to develop topical ocular delivery systems with improved ocular bioavailability and reduced systemic side effects while maintaining the dosage form’s simplicity and convenience. Methods: In the present study, the nanoparticles are prepared using ionotropic gelation method. The physiochemical interactions between drugs and selected excipients were studied using various techniques such as FTIR, DSC, XRD, and H-NMR. The physiochemical properties of the nanoparticles such as size, PDI, pH, and drug content/entrapment efficiency were determined. The in-vitro drug release properties were characteristics and examined for the formulations. The synthesize form of chitosan, that is, tri-methyl chitosan is used due to solubility issue. Result: The comparative study was done using TMC and cyclodextrin as a polymer out of which TMC polymer gives better results. The optimization is done using 32 factorial design using design expert software. The optimized batch follows the zero order release kinetics. Conclusion: TMC loaded VCZ nanoparticles show better result with improved solubility and permeability.

Layer-by-Layer Delivery of Multiple Antigens Using Trimethyl Chitosan Nanoparticles as a Malaria Vaccine Candidate.

Developing a safe and effective malaria vaccine is critical to reducing the spread and resurgence of this deadly disease, especially in children. In recent years, vaccine technology has seen expanded development of subunit protein, peptide, and nucleic acid vaccines. This is due to their inherent safety, the ability to tailor their immune response, simple storage requirements, easier production, and lower expense compared to using attenuated and inactivated organism-based approaches. However, these new vaccine technologies generally have low efficacy. Subunit vaccines, due to their weak immunogenicity, often necessitate advanced delivery vectors and/or the use of adjuvants. A new area of vaccine development involves design of synthetic micro- and nano-particles and adjuvants that can stimulate immune cells directly through their physical and chemical properties. Further, the unique and complex life cycle of the Plasmodium organism, with multiple stages and varying epitopes/antigens presented by the parasite, is another challenge for malaria vaccine development. Targeting multistage antigens simultaneously is therefore critical for an effective malaria vaccine. Here, we rationally design a layer-by-layer (LbL) antigen delivery platform (we called LbL NP) specifically engineered for malaria vaccines. A biocompatible modified chitosan nanoparticle (trimethyl chitosan, TMC) was synthesized and utilized for LbL loading and release of multiple malaria antigens from pre-erythrocytic and erythrocytic stages. LbL NP served as antigen/protein delivery vehicles and were demonstrated to induce the highest Plasmodium falciparum Circumsporozoite Protein (PfCSP) specific T-cell responses in mice studies as compared to multiple controls. From immunogenicity studies, it was concluded that two doses of intramuscular injection with a longer interval (4 weeks) than traditional malaria vaccine candidate dosing would be the vaccination potential for LbL NP vaccine candidates. Furthermore, in PfCSP/Py parasite challenge studies we demonstrated protective efficacy using LbL NP. These LbL NP provided a significant adjuvant effect since they may induce innate immune response that led to a potent adaptive immunity to mediate non-specific anti-malarial effect. Most importantly, the delivery of CSP full-length protein stimulated long-lasting protective immune responses even after the booster immunization 4 weeks later in mice.

Effects of the Combined Application of Trimethylated Chitosan and Carbodiimide on the Biostability and Antibacterial Activity of Dentin Collagen Matrix.

The structural integrity of a dentin matrix that has been demineralized by the clinical use of etchants or calcium-depleting endodontic irrigants, such as endodontic ethylenediaminetetraacetic acid (EDTA), is often deteriorated due to the collagenolytic activities of reactivated endogenous enzymes as well as the infiltration of extrinsic bacteria. Therefore, the biomodification of dentin collagen with improved stability and antibacterial activity holds great promise in conservative dentistry. The purpose of this study was to evaluate the effects of the combined application of trimethylated chitosan (TMC) and 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) on the biostability and antibacterial activity of the demineralized dentin collagen matrix. The morphological changes in the collagen matrix were observed by scanning electron microscopy (SEM), the amount of TMC adsorbed on the collagen surface was detected by X-ray photoelectron spectroscopy, and the elastic modulus was measured by a three-point bending device. Dry weight loss and amino acid release were detected to evaluate its anti-collagenase degradation performance. The antibacterial performance was detected by confocal microscopy. The TMC-treated group had less collagen space and a more compact collagen arrangement, while the untreated group had a looser collagen arrangement. The combined application of TMC and EDC can increase the elastic modulus, reduce the loss of elastic modulus, and result in good antibacterial performance. The current study proved that a dentin collagen matrix biomodified by TMC and EDC showed improved biodegradation resistance and antibacterial activities.