Low Molecular Weight Chitosan Nanoparticles Research Articles

Highly Efficient Synthesis of Type B Gelatin and Low Molecular Weight Chitosan Nanoparticles: Potential Applications as Bioactive Molecule Carriers and Cell-Penetrating Agents.

Gelatin and chitosan nanoparticles have been widely used in pharmaceutical, biomedical, and nanofood applications due to their high biocompatibility and biodegradability. This study proposed a highly efficient synthesis method for type B gelatin and low-molecular-weight (LMW) chitosan nanoparticles. Gelatin nanoparticles (GNPs) were synthesized by the double desolvation method and the chitosan nanoparticles (CNPs) by the ionic gelation method. The sizes of the obtained CNPs and GNPs (373 ± 71 nm and 244 ± 67 nm, respectively) and zeta potential (+36.60 ± 3.25 mV and −13.42 ± 1.16 mV, respectively) were determined via dynamic light scattering. Morphology and size were verified utilizing SEM and TEM images. Finally, their biocompatibility was tested to assure their potential applicability as bioactive molecule carriers and cell-penetrating agents.

FORMULATION DEVELOPMENT OF CHITOSAN NANOPARTICLES OF AMPHOTERICIN B FOR EFFECTIVE TREATMENT OF FUNGAL DISEASE

Because of the increasing prevalence and changing microbiological spectrum of invasive fungal infections, some form of amphotericin B still provides the most reliable and broad spectrum therapeutic alternative. The research aimed to formulate and prepare chitosan nanaoparticle incorporated gel of low molecular weight chitosan nanoparticles with the help of antifungal agents amphotericin B for the topical application. Using the ionic gelation process, nanoparticles containing drugs were prepared. By cationic interaction is suitable for pH, and gel sodium tripolyphosphate is used as a crosslinker which cross-links the chitosan particles to form the gel, interaction between drug and polymer was observed during the formulation development. The gel was prepared and evaluated for viscosity, % assay, extrudability, spreadability and drug release study. It was found that viscosity of prepared gel was 4520cps, % assay was 98.96±0.35, Extrudability was 167g and Spreadibility (g.cm/sec) was found that 11.95 (g.cm/sec) respectively table 3. In vitro drug release from chitosan nanoparticles gel was carried out using Franz diffusion cell method and found 92.23% in 12 hr.

Low molecular weight chitosan nanoparticles for CpG oligodeoxynucleotides delivery: Impact of molecular weight, degree of deacetylation, and mannosylation on intracellular uptake and cytokine induction

Although synthetic CpG oligodeoxynucleotides (ODNs) have shown substantial potential as immunotherapeutic agents, their effective intracellular delivery remains challenging. In this work, nanoparticles prepared from low-molecular weight (LMW) chitosans were investigated as CpG ODN delivery systems. Chitosan samples with a molecular weight (Mw) of 5 and 15 kDa and degree of deacetylation (DDA) of 50 and 80% were prepared. Additionally, mannosylated chitosans with a substitution degree of 15% were synthesized. The impact of LMW chitosan Mw and DDA on nanoparticle physical properties and the associated immunostimulatory effect in RAW 264.7 cells was studied. Nanoparticles prepared with chitosan of higher DDA and larger Mw exhibited better CpG ODN binding ability and intracellular uptake. Nevertheless, the most efficient immunostimulatory effect was observed while using 50% acetylated and mannosylated samples. The decreased charge density on chitosan backbone resulted in the enhanced intracellular CpG ODN release, which promoted in vitro cytokine secretion. Moreover, mannose ligand grafting promoted nanoparticle uptake through receptor-mediated recognition. Overall, this research suggests that chitosan structural parameters can be modulated to prepare LMW chitosan nanoparticles that first efficiently encapsulate CpG ODN, and then release it in immune cells, thus may be used as an efficient vector for intracellular CpG ODN delivery.

Formulation and evaluation of antifungal agent in a hydrogel containing nanoparticle of low molecular weight chitosan

The research aimed to formulate and prepare hydrogel of low molecular weight chitosan nanoparticles with the help of antifungal agents such as clotrimazole and Nystatin for the topical application. Using the ionic gelation process, placebo and nanoparticles containing drugs were prepared. By cationic interaction is suitable for pH, and gel sodium tripolyphosphate is used as a crosslinker which cross-links the chitosan particles to form the gel, interaction between drug and polymer was observed during the formulation development. Formulated nanoparticle with chitosan and nystatin and clotrimazole showed the mean diameter 273.7nm, 983nm, and 501nm. Clotrimazole and Nystatin had encapsulation capacity was about 74.6% and 63.0%, respectively. In vitro drug release at pH 4.7 chitosan molecules are examined for the version of clotrimazole and nystatin.it has noticed that both the formulation shows sustained drug release about 12 hours. Using SEM, nanoparticles are directed for surface morphology character; it shows that nanoparticles are smooth and spherical in structure. Chitosan itself has the antimicrobial property; it was carried out for the antifungal activity against the fungus Candida Albicans along with the prepared formulations drugs for the comparative study. And the result showed that clotrimazole had maximum fungal growth inhibition next followed by the nystatin and chitosan is least. This inhibitory effect was due to the parameter such as zeta potential and particle size of chitosan nanoparticles. And it shows the least antifungal activity of nanoparticles, which are formulated from the TMC. Hence CTZ and Chitosan were formulated and applied as a natural antifungal agent into nanoparticle to increase the fungal activity. According to the ICH Q1A (R2) guidelines, stability studies are conducted to prove no degradation of the drug. The prepared formulation of chitosan nanoparticles based hydrogel incorporated with clotrimazole and nystatin are promising and significant properties for the efficient treatment of topical fungal infections

Enhancing the Thermo-Stability and Anti-Biofilm Activity of Alginate Lyase by Immobilization on Low Molecular Weight Chitosan Nanoparticles.

Bacterial biofilm causes severe antibiotic resistance. An extracellular polymeric substance (EPS) is the main component in the bacterial biofilm. Alginate is a key EPS component in the biofilm of Pseudomonas aeruginosa and responsible for surface adhesion and stabilization of biofilm. Alginate lyase has emerged as an efficient therapeutic strategy targeting to degrade the alginate in the biofilm of P. aeruginosa. However, the application of this enzyme is limited by its poor stability. In this study, chitosan nanoparticles (CS-NPs) were synthesized using low molecular weight chitosan and alginate lyase Aly08 was immobilized on low molecular weight chitosan nanoparticles (AL-LMW-CS-NPs). As a result, the immobilization significantly enhanced the thermal stability and reusability of Aly08. In addition, compared with free Aly08, the immobilized AL-LMW-CS-NPs exhibited higher efficiency in inhibiting biofilm formation and interrupting the established mature biofilm of P. aeruginosa, which could reduce its biomass and thickness confirmed by confocal microscopy. Moreover, the biofilm disruption greatly increased the antibiotic sensitivity of P. aeruginosa. This research will contribute to the further development of alginate lyase as an anti-biofilm agent.

Chitosan nanoparticles as alternative anti-staphylococci agents: Bactericidal, antibiofilm and antiadhesive effects

Chitosan is a biocompatible, bioactive, non-toxic polymer that due to these characteristics has been widely used as a carrier for targeted delivery of bioactive molecules. In recent years, and considering that chitosan has a strong antimicrobial potential, the scientific community's focus has shifted onto the possible antimicrobial activity of chitosan nanoparticles. With this in mind, the aim of this work was to produce low molecular weight chitosan nanoparticles, through the ionic gelation method and characterize their potential biological activity against three staphylococci (MSSA, MRSA and MRSE) in planktonic and sessile environments. The chitosan nanoparticles produced had an average size of 244±12nm, an average charge of 17.3±1.4mV and had a MIC of 1.25mg/mL for all tested microorganisms. Bactericidal activity was only registered for MSSA and MRSA with the time-inhibition curves showing bactericidal activity within 1h. Assays regarding chitosan nanoparticles' impact upon sessile populations showed that they were effective in preventing MRSE adhesion and highly effective in reducing MRSA and MSSA biofilm formation.

Effect of low-intensity pulsed ultrasound on biocompatibility and cellular uptake of chitosan-tripolyphosphate nanoparticles.

Using low molecular weight chitosan nanoparticles (CNPs) prepared by an ionic gelation method, the authors report the effect of low-intensity pulsed ultrasound (US) on cell viability and nanoparticle uptake in cultured murine preosteoblasts. Particle size and zeta potential are measured using dynamic light scattering, and cell viability is evaluated using the of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] assay. Results show that 30 min delivery of CNPs at 0.5 mg/mL is able to prevent loss of cell viability due to either serum starvation or subsequent exposure to US (1 W/cm(2) or 2 W/cm(2), up to 1 min). Additionally, flow cytometry data suggest that there is a close association between cellular membrane integrity and the presence of CNPs when US at 2 W/cm(2) is administered.

Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine

The present study was focused to prepare controlled release glycyrrhizin (GL) conjugated low molecular weight chitosan nanoparticles (CS-NPs) for liver targeting. The hydrophilic antiretroviral drug lamivudine was chosen as a model drug and encapsulated within glycyrrhizin conjugated low molecular weight chitosan nanoparticles (GL-CS-NPs) for liver specificity. First, the low molecular weight chitosan (CS) was synthesized through depolymerization method. The low molecular weight chitosan nanoparticles were prepared by inotropic gelation method. Then glycyrrhizin was conjugated with previously prepared low molecular weight chitosan nanoparticles (CS-NPs) and conjugation was confirmed by Fourier transform infrared (FT-IR) spectroscopy. The prepared GL-CS-NPs were characterized using dynamic light scattering, transmission electron microscopy and FT-IR. The encapsulation efficiency and in-vitro drug release behaviour of drug-loaded GL-CS-NPs were studied using ultra violet spectroscopy and high performance liquid chromatographic methods. Release of lamivudine from the nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. In-vivo biodistribution study suggested the target ability of GL-CS-NPs is better and haematological study shows decline of the tissue damage in comparison with plain drug solution. The experimental results show that the glycyrrhizin conjugated LMWC nanoparticles may be used as a potential drug delivery system with hepatocyte-targeting characteristics.

Erythrocytes load of low molecular weight chitosan nanoparticles as a potential vascular drug delivery system

Low molecular weight (LMW) chitosan nanoparticles have attracted considerable attention as colloidal drug carriers, but when applied to intravascular drug delivery, they are easy to be removed from circulation by the reticuloendothelial system, which limits their applications as long-circulating or target-specific carriers. Erythrocytes have a long circulation time in the blood, but they are sometimes not suitable for loading and releasing of drug directly. The combination of LMW chitosan nanoparticles and erythrocytes that complement each other is a desirable strategy to develop a multifunctional drug carrier. In this study, monodisperse, LMW chitosan nanoparticles were prepared by ionic gelation technique and these nanoparticles were investigated with regard to their erythrocyte compatibility. Then the interactions between erythrocytes and fluorescence-labeled LMW chitosan nanoparticles were studied by confocal microscopy. The results of this study indicate that LMW chitosan nanoparticles show good compatibility with erythrocytes and they can be easily attached to the surface of erythrocyte membrane, suggesting that erythrocytes load of LMW chitosan nanoparticles can be served as a potential vascular drug delivery system.

Low molecular weight chitosan nanoparticulate system at low N:P ratio for nontoxic polynucleotide delivery

Chitosan, a natural polymer, is a promising system for the therapeutic delivery of both plasmid DNA and synthetic small interfering RNA. Reports attempting to identify the optimal parameters of chitosan for synthetic small interfering RNA delivery were inconclusive with high molecular weight at high amine-to-phosphate (N:P) ratios apparently required for efficient transfection. Here we show, for the first time, that low molecular weight chitosan (LMW-CS) formulations at low N:P ratios are suitable for the in vitro delivery of small interfering RNA. LMW-CS nanoparticles at low N:P ratios were positively charged (ζ-potential ~20 mV) with an average size below 100 nm as demonstrated by dynamic light scattering and environmental scanning electron microscopy, respectively. Nanoparticles were spherical, a shape promoting decreased cytotoxicity and enhanced cellular uptake. Nanoparticle stability was effective for at least 20 hours at N:P ratios above two in a slightly acidic pH of 6.5. At a higher basic pH of 8, these nanoparticles were unravelled due to chitosan neutralization, exposing their polynucleotide cargo. Cellular uptake ranged from 50% to 95% in six different cell lines as measured by cytometry. Increasing chitosan molecular weight improved nanoparticle stability as well as the ability of nanoparticles to protect the oligonucleotide cargo from nucleases at supraphysiological concentrations. The highest knockdown efficiency was obtained with the specific formulation 92-10-5 that combines sufficient nuclease protection with effective intracellular release. This system attained >70% knockdown of the messenger RNA, similar to commercially available lipoplexes, without apparent cytotoxicity. Contrary to previous reports, our data demonstrate that LMW-CS at low N:P ratios are efficient and nontoxic polynucleotide delivery systems capable of transfecting a plethora of cell lines.

Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique

Chitosan nanoparticles have been extensively studied for drug and gene delivery. In this paper, monodisperse, low molecular weight (LMW) chitosan nanoparticles were prepared by a novel method based on ionic gelation using sodium tripolyphosphate (TPP) as cross-linking agent. The objective of this study was to solve the problem of preparation of chitosan/TPP nanoparticles with high degree of monodispersity and stability, and investigate the effect of various parameters on the formation of LMW chitosan/TPP nanoparticles. It was found that the particle size distribution of the nanoparticles could be significantly narrowed by a combination of decreasing the concentration of acetic acid and reducing the ambient temperature during cross-linking process. The optimized nanoparticles exhibited a mean hydrodynamic diameter of 138 nm with a polydispersity index (PDI) of 0.026 and a zeta potential of +35 mV, the nanoparticles had good storage stability at room temperature up to at least 20 days.

Nanotechnology for therapy and imaging of liver diseases

Nanotechnology has been considered for the improved delivery of various therapeutic agents, including drugs and genes. Indeed, liposomes and nanoparticles equipped with homing devices for the targeting of receptors over-expressed on the hepatic tissue have improved the treatment of various liver diseases. In this review, various nanotechnology approaches employed for the treatment/imaging of liver disease, either in preclinical or in clinic are discussed.

Targeted Delivery of Doxorubicin to Hepatocytes via Galactosylated Low Molecular Weight Chitosan Nanoparticles

Targeted Delivery of Doxorubicin to Hepatocytes via Galactosylated Low Molecular Weight Chitosan Nanoparticles

Development and In Vitro Characterization of Galactosylated Low Molecular Weight Chitosan Nanoparticles Bearing Doxorubicin

The aim of the present research was to evaluate the potential of galactosylated low molecular weight chitosan (Gal-LMWC) nanoparticles bearing positively charged anticancer, doxorubicin (DOX) for hepatocyte targeting. The chitosan from crab shell was depolymerized, and the lactobionic acid was coupled with LMWC using carbodiimide chemistry. The depolymerized and galactosylated polymers were characterized. Two types of Gal-LMWC(s) with variable degree of substitution were employed to prepare the nanoparticles using ionotropic gelation with pentasodium tripolyphosphate anions. Factors affecting nanoparticles formation were discussed. The nanoparticles were characterized by transmission electron microscopy and photon correlation spectroscopy and found to be spherical in the size range 106-320 nm. Relatively higher percent DOX entrapment was obtained for Gal-LMWC(s) nanoparticles than for LMWC nanoparticles. A further increase in drug entrapment was found with nanoparticles prepared by Gal-LMWC with higher degree of substitution. A hypothesis which correlates the ionic concentration of DOX in nanoparticles preparation medium and percent DOX entrapment in cationic polymer has been proposed to explain the enhanced DOX entrapment. In-vitro drug release study demonstrated an initial burst release followed by a sustained release. The targeting potential of the prepared nanoparticles was assessed by in vitro cytotoxicity study using the human hepatocellular carcinoma cell line (HepG(2)) expressing the ASGP receptors on their surfaces. The enthusiastic results showed the feasibility of Gal-LMWC(s) to entrap the cationic DOX and targeting potential of developed Gal-LMWC(s) nanoparticles to HepG(2) cell line.