Chitosan-based Carriers Research Articles

Investigation of a novel bilayered PCL/PVA electrospun nanofiber incorporated Chitosan-LL37 and Chitosan-VEGF nanoparticles as an advanced antibacterial cell growth-promoting wound dressing

Chronic wounds have become a growing concern as they can have a profound impact on individuals, potentially resulting in mortality. It is crucial to prevent and manage bacterial infections, particularly drug-resistant ones. Antimicrobial peptides, such as LL-37, can firmly eliminate pathogens. Additionally, the process of angiogenesis, facilitated by growth factors like VEGF, is essential for tissue repair and wound healing. To enhance the stability and bioavailability of therapeutic agents, targeted delivery strategies utilizing Chitosan-based carriers have been employed. Electrospun biopolymers in advanced wound dressings have revolutionized wound care by providing a more effective and efficient solution for promoting tissue regeneration and speeding up the healing process. The present investigation utilized Chitosan nanoparticles to encapsulate the recombinant LL37 peptide and VEGF. An in-depth investigation was carried out to analyze the biophysical and morphological traits of the LL37-CSNPs and VEGF-CSNPs. The first support layer consisted of PCL electrospun nanofiber, followed by the electrospinning of PVA/CsLL37, PVA/CsVEGF, and PVA/CsLL37/CsVEGF onto the PCL layer. An in vitro examination assessed the fabricated nanofibers’ morphological, mechanical, and biological characteristics. The antimicrobial effects were tested on methicillin-resistant Staphylococcus aureus (MRSA). The in vivo experiments assessed the antibacterial and wound-healing capabilities of the nanofibers. The findings validated the continuous release of LL37 and VEGF. The composite material PCL/PVA/CsLL37/CsVEGF demonstrated potent bactericidal and antioxidant characteristics. The cytotoxic assay demonstrated the biocompatibility of the fabricated nano mats and their potential to accelerate fibroblast cell proliferation. The efficacy of PVA/CsLL37/CsVEGF in promoting wound healing was confirmed through an in vivo wound healing assay. Furthermore, the histological analysis provided evidence of faster epidermal formation and improved antibacterial activity in wounds covered with PVA/CsLL37/CsVEGF. Adding LL37 and VEGF to the composite material improves the immune response and promotes blood vessel formation, accelerating wound healing and decreasing inflammation.

Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.

Preparation and sustained release of diatomite incorporated and Eudragit L100 coated hydroxypropyl cellulose/chitosan aerogel microspheres

The drug encapsulation efficiency, release rate and time, sustained release, and stimulus-response of carriers are very important for drug delivery. However, these always cannot obtained for the carrier with a single component. To improve the comprehensive performance of chitosan-based carriers for 5-Fu delivery, diatomite-incorporated hydroxypropyl cellulose/chitosan (DE/HPC/CS) composite aerogel microspheres were fabricated for the release of 5-fluorouracil (5-Fu), and the release performance was regulated with the content of diatomite, pH value, and external coating material. Firstly, the 5-Fu loaded DE/HPC/CS composite aerogel microspheres and Eudragit L100 coated microspheres were prepared with cross-linking followed by freeze-drying, and characterized by SEM, EDS, FTIR, XRD, DSC, TG, and swelling. The obtained aerogel microspheres have a diameter of about 0.5 mm, the weight percentage of F and Si elements on the surface are 0.55 % and 0.78 % respectively. The glass transition temperature increased from 179 °C to 181 °C and 185 °C with the incorporation of DE and coating of Eudragit, and the equilibrium swelling percentage of DE/HPC/CS (1.5:3:2) carriers are 101.52 %, 45.27 %, 67.32 % at pH 1.2, 5.0, 7.4, respectively. Then, the effect of DE content on the drug loading efficiency of DE/HPC/CS@5-Fu was investigated, with the increase of DE content, the highest encapsulation efficiency was 82.6 %. Finally, the release behavior of DE incorporated and Eudragit L100 Coated microspheres were investigated under different pH values, and evaluated with four kinetic models. The results revealed that the release rate of 5-Fu decreased with the increase of DE content, sustained release with extending time and pH-responsive were observed for the Eudragit-coated aerogel microspheres.

Immobilization on Polyethylenimine and Chitosan Sorbents Modulates the Production of Valuable Fatty Acids by the Chlorophyte Lobosphaera sp. IPPAS C-2047

Green microalgae, including those from the genus Lobosphaera, are exploited in various fields of biotechnology to obtain valuable fatty acids (e.g., arachidonic acid (C20:4, ARA)) for the production of infant formulae, food and feed additives. In nature, microalgae frequently exist in naturally immobilized state (as biofilms) with a limited cell division rate and increased stress resilience. In the fields of biotechnology, immobilization of microalgae on artificial cell carriers simplifies biomass harvesting and increases culture robustness and productivity. The choice of a suitable cell carrier is central to biotechnology involving immobilized cultures. Cell carriers based on the natural amine-containing polymer chitosan and synthetic polyethylenimine (PEI) are promising candidates for immobilization of phototrophic microorganisms. This is the first report on the effects of immobilization on PEI and chitosan on the accumulation and composition of polyunsaturated fatty acids, including ARA, in Lobosphaera sp. IPPAS C-2047. Immobilization on PEI increased the ARA percentage in the total fatty acids and ARA accumulation by 72% and 81% compared to the suspended cells cultured in complete or nitrogen-deprived medium 14 days, respectively. Immobilization of Lobosphaera sp. on the chitosan-based carrier reduced the ARA percentage but increased oleic and α-linoleic acid percentages. The mechanisms of the effects of immobilization on the fatty acid profiles of the microalgae are discussed.

Impact of Degree of Ionization and PEGylation on the Stability of Nanoparticles of Chitosan Derivatives at Physiological Conditions.

Nowadays, the therapeutic efficiency of small interfering RNAs (siRNA) is still limited by the efficiency of gene therapy vectors capable of carrying them inside the target cells. In this study, siRNA nanocarriers based on low molecular weight chitosan grafted with increasing proportions (5 to 55%) of diisopropylethylamine (DIPEA) groups were developed, which allowed precise control of the degree of ionization of the polycations at pH 7.4. This approach made obtaining siRNA nanocarriers with small sizes (100–200 nm), positive surface charge and enhanced colloidal stability (up to 24 h) at physiological conditions of pH (7.4) and ionic strength (150 mmol L−1) possible. Moreover, the PEGylation improved the stability of the nanoparticles, which maintained their colloidal stability and nanometric sizes even in an albumin-containing medium. The chitosan-derivatives displayed non-cytotoxic effects in both fibroblasts (NIH/3T3) and macrophages (RAW 264.7) at high N/P ratios and polymer concentrations (up to 0.5 g L−1). Confocal microscopy showed a successful uptake of nanocarriers by RAW 264.7 macrophages and a promising ability to silence green fluorescent protein (GFP) in HeLa cells. These results were confirmed by a high level of tumor necrosis factor-α (TNFα) knockdown (higher than 60%) in LPS-stimulated macrophages treated with the siRNA-loaded nanoparticles even in the FBS-containing medium, findings that reveal a good correlation between the degree of ionization of the polycations and the physicochemical properties of nanocarriers. Overall, this study provides an approach to enhance siRNA condensation by chitosan-based carriers and highlights the potential of these nanocarriers for in vivo studies.

Effects of Formulation on the Palatability and Efficacy of In-Feed Praziquantel Medications for Marine Finfish Aquaculture.

Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1–4 mm) were developed using marine-based polymers, with allicin added as a flavouring agent. All formulations attained PZQ loading rates ≥74% w/w, and the beads were successfully incorporated into fish feed pellets at an active dietary inclusion level of 10 g/kg. When tested for palatability and digestibility in small yellowtail kingfish, the PZQ-loaded beads produced with alginate-chitosan, alginate-Cremophor® RH40, and agar as carriers resulted in high consumption rates of 99–100% with no digesta or evidence of beads in the gastrointestinal tract (GIT) of fish fed with diets containing either formulation. Two formulations produced using chitosan-based carriers resulted in lower consumption rates of 68–75%, with undigested and partly digested beads found in the fish GIT 3 h post feeding. The PZQ-loaded alginate-chitosan and agar beads also showed good palatability in large (≥2 kg) yellowtail kingfish infected with gill parasites and were efficacious in removing the parasites from the fish, achieving >90% reduction in mean abundance relative to control fish (p < 0.001). The two effective formulations were stable upon storage at ambient temperature for up to 18 months, showing residual drug content >90% compared with baseline levels. Overall, the palatability, efficacy and stability data collected from this study suggest that these two PZQ particulate formulations have potential applications as in-feed anti-parasitic medications for the yellowtail kingfish farming industry.

Lipid Coating of Chitosan Nanogels for Improved Colloidal Stability and In Vitro Biocompatibility.

Chitosan-based carriers have coined their position as delivery agents. When assembled with polyanions into nanogels (NG), these vectors have enabled the delivery of drugs, genes, and proteins to a myriad of applications. However, the chemical and colloidal instability of chitosan nanoformulations in physiologically compatible media prejudices in vitro biocompatibility and, thus, scale-up applications. To overcome this issue, we envisaged the coating of chitosan nanogel with phospholipids. In this investigation, we report a two-stage synthesis of hybrid lipid-coated chitosan nanogels, named nanolipogels (NLG), to improve colloidal stability and in vitro biocompatibility over chitosan NG. Practically, we employed a mixing platform to first prepare chitosan NG by ionic gelation, dilute the suspension, and, in a second stage, coat the NG with lipids. We demonstrate that lipid coating increased particle size and reversed the ζ-potential to negative values, suggesting the successful formation of NLG, while maintaining a homogeneous size distribution (PDI < 0.25). Furthermore, multiple light scattering analysis confirmed NLG improved colloidal stability in phosphate buffer saline and cell culture medium, with respect to NG. Finally, lipid coating completely abrogated the cytotoxicity of NG when incubated at 50 μg·mL-1 with HeLa, U87, or b.End3 cell lines and significantly improved the biocompatibility at 100 and 150 μg·mL-1. Future investigations will explore how the lipid coating affects drug loading, release profile, and the ability of NLG to deliver drugs and genes in vitro.

Chitosan Activated with Genipin: A Nontoxic Natural Carrier for Tannase Immobilization and Its Application in Enhancing Biological Activities of Tea Extract.

In this work, a non-toxic chitosan-based carrier was constructed via genipin activation and applied for the immobilization of tannase. The immobilization carriers and immobilized tannase were characterized using Fourier transform infrared spectroscopy and thermogravimetric analysis. Activation conditions (genipin concentration, activation temperature, activation pH and activation time) and immobilizations conditions (enzyme amount, immobilization time, immobilization temperature, immobilization pH, and shaking speed) were optimized. The activity and activity recovery rate of the immobilized tannase prepared using optimal activation and immobilization conditions reached 29.2 U/g and 53.6%, respectively. The immobilized tannase exhibited better environmental adaptability and stability. The immobilized tannase retained 20.1% of the initial activity after 12 cycles and retained 81.12% of residual activity after 30 days storage. The catechins composition analysis of tea extract indicated that the concentration of non-ester-type catechins, EGC and EC, were increased by 1758% and 807% after enzymatic treatment. Biological activity studies of tea extract revealed that tea extract treated with the immobilized tannase possessed higher antioxidant activity, higher inhibitory effect on α-amylase, and lower inhibitory effect on α-glucosidase. Our results demonstrate that chitosan activated with genipin could be an effective non-toxic carrier for tannase immobilization and enhancing biological activities of tea extract.

The Development, Evaluation, and Antioxidant Activity Analysis of Chitosan Microcapsules Containing Red Ginger Oleoresin with Sodium Tripolyphosphate Prepared by Emulsion Cross-linking Technique

In this study, chitosan-based carrier of red ginger oleoresin was prepared using the emulsion cross-linking technique with sodium tripolyphosphate (TPP) as a cross-linking agent. The effect of chitosan and TPP concentration, as well as pH on the encapsulation efficiency, particle size and characterization of chitosan microcapsule was determined. The antioxidant activity of microcapsules was analyzed. Chitosan microcapsules containing red ginger oleoresin were produced although with non-smooth surfaces.

Bio-inspired materials for nutrient biocapture from wastewater: Microalgal cells immobilized on chitosan-based carriers

The successful application of the cross-linked chitosan-based polymers for microalgae immobilization and biocapture of nutrients is reported for the first time. Highly porous, hydrophilic polymers were obtained by cross-linking of 250 kDa or 600 kDa chitosan with glutaraldehyde. Both cross-linked chitosan polymers were characterized by high microalgae immobilization efficiency and supported the prolonged cultivation of immobilized Lobosphaera sp. IPPAS 2047 cells without impairing their growth and photosynthetic activity. The 600 kDA chitosan-based polymers demonstrated higher mechanical and biological stability during 7 d incubation than those based on the 250 kDa chitosan. The nutrient removal capacity of the chitosan-immobilized Lobosphaera cells was significantly higher as compared to that of the suspended cells. The specific removal rates of inorganic phosphate and nitrate by the suspended microalgae cells cultivated without cross-linked chitosan polymers comprised 0.36 and 0.50 mg mg−1 Chl d−1, while the chitosan-immobilized Lobosphaera cells consumed phosphate and nitrate at rates 6.01 and 0.65 mg mg−1 Chl d−1, respectively. Collectively, the cross-linked chitosan-based polymers were shown to be environment-friendly materials providing the enhancement of nutrients bioremoval from wastewater by immobilized microalgae cells. The nutrient-enriched microalgae biomass immobilized on the biodegradable and non-toxic chitosan carriers can be applied as slow-releasing biofertilizer.

Co-delivery of free vancomycin and transcription factor decoy-nanostructured lipid carriers can enhance inhibition of methicillin resistant Staphylococcus aureus (MRSA).

Bacterial resistance to antibiotics is widely regarded as a major public health concern with last resort MRSA treatments like vancomycin now encountering resistant strains. TFDs (Transcription Factor Decoys) are oligonucleotide copies of the DNA-binding sites for transcription factors. They bind to and sequester the targeted transcription factor, thus inhibiting transcription of many genes. By developing TFDs with sequences aimed at inhibiting transcription factors controlling the expression of highly conserved bacterial cell wall proteins, TFDs present as a potential method for inhibiting microbial growth without encountering typical resistance mechanisms. However, the efficient protection and delivery of the TFDs inside the bacterial cells is a critical step for the success of this technology. Therefore, in our study, specific TFDs against S. aureus were complexed with two different types of nanocarriers: cationic nanostructured lipid carriers (cNLCs) and chitosan-based nanoparticles (CS-NCs). These TFD-carrier nanocomplexes were characterized for size, zeta potential and TFD complexation or loading efficiency in a variety of buffers. In vitro activity of the nanocomplexes was examined alone and in combination with vancomycin, first in methicillin susceptible strains of S. aureus with the lead candidate advancing to tests against MRSA cultures. Results found that both cNLCs and chitosan-based carriers were adept at complexing and protecting TFDs in a range of physiological and microbiological buffers up to 72 hours. From initial testing, chitosan-TFD particles demonstrated no visible improvements in effect when co-administered with vancomycin. However, co-delivery of cNLC-TFD with vancomycin reduced the MIC of vancomycin by over 50% in MSSA and resulted in significant decreases in viability compared with vancomycin alone in MRSA cultures. Furthermore, these TFD-loaded particles demonstrated very low levels of cytotoxicity and haemolysis in vitro. To our knowledge, this is the first attempt at a combined antibiotic/oligonucleotide-TFD approach to combatting MRSA and, as such, highlights a new avenue of MRSA treatment combining traditional small molecules drugs and bacterial gene inhibition.

Recent Advances in Chitosan-Based Carriers for Gene Delivery

Approximately 4000 diseases are associated with malfunctioning genes in a particular cell type. Gene-based therapy provides a platform to modify the disease-causing genes expression at the cellular level to treat pathological conditions. However, gene delivery is challenging as these therapeutic genes need to overcome several physiological and intracellular barriers in order, to reach the target cells. Over the years, efforts have been dedicated to develop efficient gene delivery vectors to overcome these systemic barriers. Chitosan, a versatile polysaccharide, is an attractive non-viral vector material for gene delivery mainly due to its cationic nature, biodegradability and biocompatibility. The present review discusses the design factors that are critical for efficient gene delivery/transfection and highlights the recent progress of gene therapy using chitosan-based carriers.

Chitosan-Based Nanocarriers for Nose to Brain Delivery

In the treatment of brain diseases, most potent drugs that have been developed exhibit poor therapeutic outcomes resulting from the inability of a therapeutic amount of the drug to reach the brain. These drugs do not exhibit targeted drug delivery mechanisms, resulting in a high concentration of the drugs in vital organs leading to drug toxicity. Chitosan (CS) is a natural-based polymer. It has unique properties such as good biodegradability, biocompatibility, mucoadhesive properties, and it has been approved for biomedical applications. It has been used to develop nanocarriers for brain targeting via intranasal administration. Nanocarriers such as nanoparticles, in situ gels, nanoemulsions, and liposomes have been developed. In vitro and in vivo studies revealed that these nanocarriers exhibited enhanced drug uptake to the brain with reduced side effects resulting from the prolonged contact time of the nanocarriers with the nasal mucosa, the surface charge of the nanocarriers, the nano size of the nanocarriers, and their capability to stretch the tight junctions within the nasal mucosa. The aforementioned unique properties make chitosan a potential material for the development of nanocarriers for targeted drug delivery to the brain. This review will focus on chitosan-based carriers for brain targeting.

A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex

The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7-10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.

Potential of chitosan-based carrier for periodontal drug delivery.

Periodontal diseases are chronic infectious diseases and are a major oral health burden. With the progress in the understanding of etiology, epidemiology and pathogenesis of periodontal diseases coupled with the understanding of the polymicrobial synergy in the dysbiotic oral microbial flora, several new therapeutic targets have been identified. The strategies to curb bacterial growth and production of factors that gradually destroy the tissue surrounding and supporting the teeth have been the cornerstone for inhibiting periodontitis. Systemic administration of antibiotics for the treatment of periodontitis have shown several drawbacks including: inadequate antibiotic concentration at the site of the periodontal pocket, a rapid decline of the plasma antibiotic concentration to sub-therapeutic levels, the development of microbial resistance due to sub-therapeutic drug levels and peak-plasma antibiotic concentrations which may be associated with various side effects. These obvious disadvantages have evoked an interest in the development of localized drug delivery systems that can provide an effective concentration of antibiotic at the periodontal site for the duration of the treatment with minimal side effects. A targeted sustained release device which could be inserted in the periodontal pocket and prolong the therapeutic levels at the site of action at a much lower dose is the need of the hour. Chitosan, a deacetylated derivative of chitin has attracted considerable attention owing to its special properties including antimicrobial efficacy, biodegradability, biocompatibility and non-toxicity. It also has the propensity to act as hydrating agent and display tissue healing and osteoinducting effect. The aim of this review is to shine a spotlight on the chitosan based devices developed for drug delivery application in the effective treatment of various periodontal disorders. The chitosan based carriers like fibers, films, sponge, microparticles, nanoparticles, gels that have been designed for sustained release of drug into the periodontal pocket are highlighted.

Osteogenic effectiveness of photo-immobilized bone morphogenetic protein-2 using different azidophenyl-natural polymer carriers in rat calvarial defect model

The osteogenetic potential of photo-immobilized azdiophenyl (Az)-natural polymers as a carrier of bone morphogenetic protein-2 (BMP-2) was assessed in 56 rats randomized to four groups. The control group comprised implanted collagen sheet with BMP-2. In the three experimental groups, the implant comprised collagen sheet with photo-immobilized BMP-2 on Az-gelatin (Az-Gel), Az-O-carboxymethyl chitosan (Az-OMC), or Az‑O‑carboxymethyl low molecular chitosan (Az-LMC). Micro-computed tomography analysis revealed more regenerated bone in Az-Gel at 8weeks. Immunohistochemical analysis at 4weeks revealed that the positively expressed cellular ratio in RUNX2-stained cells was significantly higher in Az-Gel and Az-OMC groups. At 8weeks, only the Az-Gel group showed higher positively expressed cellular ratio compared with the control group. These results demonstrate the superior osteogenetic potential of photo-immobilized BMP-2 using Az-Gel carrier in a rat calvarial defect model compared with control group. Photo-immobilization of BMP-2 using Az-gelatin could be a more effective carrier system of BMP-2 than a chitosan-based carrier system.

MUCOADHESIVE CHITOSAN MICROSPHERES OF GEFITINIB

Objective: Gefitinib, Epidermal Growth Factor-Tyrosine Kinase Inhibitor (EGFR-TKI); has promisingly shown activity against Non-Small-Scale Lung Cancer. Currently, the formulations of this drug available are in Tablets, Capsules and liposomal suspensions taken by the oral route. These have certain disadvantages in gastrointestinal disorders like irritation of GI mucosal layer, bleeding, non-patient compliance and low bioavailability due to low aqueous solubility and thus low bioavailability. The purpose of this study was to formulate and evaluate Chitosan-based Microparticles of Gefitinib for maintaining the therapeutic index and limits its side effects.Methods: Chitosan microspheres cross-linked with glutaraldehyde were prepared by solvent evaporation technique which is then analyzed for its particle size, encapsulation efficiency, swelling index.Results: The release rate of the drug can be increased by using chitosan-based carrier system which will enhance its bioavailability. By this work, the anticancer activity of Gefitinib in non-small-scale lung cancer will be successfully determined.Conclusion: It has been concluded that microspheres can be prepared by solvent evaporation technique by varying the concentration of chitosan and tween-20. Chitosan used in this work is of 85 % degree of deacetylation, 25 % solution of Gluteraldehyde suitable for the formulation of these microspheres. Optimized temperature was selected as 65 °C, and the rotation speed was taken as 1200 rpm. Finally, the objectives planned for this research work was performed and evaluated and shown promising results as the dosing frequency is reduced and maximize for 3 d rather than once in a day as per the current formulation available in the market now with a low dosage regimen of 100 mg of dosage strength, administer by pulmonary route. Microparticulate drug delivery system from microspheres is able to deliver the drug in a sustained release manner for the long period of time successfully.

Influence of pH and aurate/amino acid ratios on the tuneable optical features of gold nanoparticles and nanoclusters

Blue- and green-emitting gold nanostructures have been synthesized by spontaneous interactions of the tetrachloroaurate anions (AuCl4−) with L-histidine (His) and L-tryptophan (Trp) at 37°C in aqueous medium. The dominant role of AuCl4−/amino acid molar ratios as well as the pH in the formation of gold nanoparticles (Au NPs) or nanoclusters (Au NCs) was confirmed by numerous spectroscopic techniques. We demonstrate that without additional reducing agents the His and Trp show different reduction behaviour with AuCl4− which supports the fact that the unique optical features originate from diverse structures. Because of the pH-dependent complexation and reduction capability of the studied amino acids the dominant presence of polynuclear fluorescent gold(I) complexes (quantum yield (QY%) ∼4%) with a well-ordered structure is presumable for His-directed Au system confirmed by mass spectrometry, X-ray diffraction and infrared experiments. The existence of d=8 nm-sized Au NPs or subnanometer-sized (d<2nm) Au NCs (Au3-Au5) that have tuneable blue or green photoluminescence (λemission=470–500nm) was identified in the samples containing Trp depending on the applied AuCl4−/Trp ratios. The blue-emitting Au/His nanohybrid system as potential bioimaging agent was used to visualize fluorescently albumin- and chitosan-based carrier composite particles.

Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.

Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives.

Controlling Properties and Cytotoxicity of Chitosan Nanocapsules by Chemical Grafting.

The tunability of the properties of chitosan-based carriers opens new ways for the application of drugs with low water-stability or high adverse effects. In this work, the combination of a nanoemulsion with a chitosan hydrogel coating and the following poly (ethylene glycol) (PEG) grafting is proven to be a promising strategy to obtain a flexible and versatile nanocarrier with an improved stability. Thanks to chitosan amino groups, a new easy and reproducible method to obtain nanocapsule grafting with PEG has been developed in this work, allowing a very good control and tunability of the properties of nanocapsule surface. Two different PEG densities of coverage are studied and the nanocapsule systems obtained are characterized at all steps of the optimization in terms of diameter, Z potential and surface charge (amino group analysis). Results obtained are compatible with a conformation of PEG molecules laying adsorbed on nanoparticle surface after covalent linking through their amino terminal moiety. An improvement in nanocapsule stability in physiological medium is observed with the highest PEG coverage density obtained. Cytotoxicity tests also demonstrate that grafting with PEG is an effective strategy to modulate the cytotoxicity of developed nanocapsules. Such results indicate the suitability of chitosan as protective coating for future studies oriented toward drug delivery.