scholarly journals Synthesis of a New Potential Conjugated TAT-Peptide-Chitosan Nanoparticles Carrier via Disulphide Linkage

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Haliza Katas ◽  
Nik Nur Shamiha Nik Dzulkefli ◽  
Shariza Sahudin
Keyword(s):  
Plasmid Dna ◽  
Size Range ◽  
Chitosan Nanoparticles ◽  
Tat Peptide ◽  
Raman Spectrometry ◽  
Spectrometry Analysis ◽  
Dna Oligonucleotides ◽  
Cytotoxicity Studies ◽  
Low Toxicity

Chitosan and TAT peptide have been widely investigated as delivery systems for various biomolecules such as plasmid DNA, oligonucleotides, and siRNAs. Conjugation of chitosan with TAT-peptide was therefore expected to produce a carrier with enhanced ability to facilitate cellular uptake. In this study, chitosan nanoparticles (CNs) were prepared by ionic gelation method prior to conjugation with TAT-peptide via disulphide linkage (CN-TAT). The conjugation was performed at various TAT-peptide-to-chitosan weight ratios ranging from 0.008 : 1 to 0.125 : 1. siRNA as a model biomolecule was loaded by adsorption onto the CN-TAT. Nanosize range particles were produced with a size range of less than 700 nm depending on TAT-peptide concentration used. HPLC and Raman spectrometry analysis revealed that TAT-peptide was successfully conjugated to the CN via disulphide linkage. siRNA loading efficiency for CN-TAT was 93%  ±0.01.In vitrocytotoxicity studies showed that CN-TAT has relatively low toxicity. In conclusion, TAT conjugated onto CN via disulphide linkage was successfully synthesized, and its low cytoxicity demonstrates a potential for its use as a vector for biomolecules.

scholarly journals Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Hali Bordelon ◽  
Alexandru S. Biris ◽  
Cristina M. Sabliov ◽  
W. Todd Monroe
Keyword(s):  
Nucleic Acids ◽  
Plasmid Dna ◽  
Genetic Manipulation ◽  
Chitosan Nanoparticles ◽  
Complex Surface ◽  
Surface Enhanced Raman Spectroscopy ◽  
Nucleic Acid Delivery ◽  
Label Free

Poly(D,L-lactide-co-glycolide-) (PLGA-)chitosan nanoparticles are becoming an increasingly common choice for the delivery of nucleic acids to cells for various genetic manipulation techniques. These particles are biocompatible, with tunable size and surface properties, possessing an overall positive charge that promotes complex formation with negatively charged nucleic acids. This study examines properties of the PLGA-chitosan nanoparticle/plasmid DNA complex after formation. Specifically, the study aims to determine the optimal ratio of plasmid DNA:nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within these complexes. Such characterization will be necessary for the adoption of these formulations in a clinical setting. The ability of PLGA-chitosan nanoparticles to form complexes with pDNA was evaluated by using the fluorescent intercalating due OliGreen to label free plasmid DNA. By monitoring the fluorescence at different plasmid: nanoparticle ratios, the ideal plasmid:nanoparticle ration for complete complexation of plasmid was determined to be 1:50. Surface-Enhanced Raman Spectroscopy and gel digest studies suggested that even at these optimal complexation ratios, a portion of the plasmid DNA was located on the outer complex surface. This knowledge will facilitate future investigations into the functionality of the systemin vitroandin vivo.

Sorafenib and 5-Fluorouracil Loaded Dual Drug Nanodelivery Systems for Hepatocellular Carcinoma and Colorectal Adenocarcinoma

2021 ◽  
Author(s):  
Umme Ruman ◽  
Kalaivani Buskaran ◽  
Saifullah Bullo ◽  
Georgia Pastorin ◽  
Mas Jaffri Masarudin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colorectal Adenocarcinoma ◽  
Dermal Fibroblast ◽  
Drug Loading ◽  
Chitosan Nanoparticles ◽  
Normal Human Dermal Fibroblast ◽  
Cytotoxicity Studies

Abstract Purpose: Here, we reported the sysnthesis of two clinically used drugs, 5-fluorouracil (5FU) and Sorafenib (SF)-loaded in chitosan nanoparticles and their priliminary study of therapeutics effect on hepatocellular carcinoma and colorectal adenocarcinoma cell lines. We have formulated chitosan nanoparticles (CS NPs) loaded dual (SF and 5-FU) drugs nanodelivery system for SF/5FU-CS NPs and their coating version with folic acid (FA) for SF/5FU-CS-FA NPS. Human hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (HT29) cell lines were selected for in vitro cytotoxicity studies to evaluate the preliminary anticancer efficacy of both nanoparticles.Characterization: The physiochemical characterization of SF/5FU-CS NPs and SF/5FU-CS-FA NPs were investigated by DLS, FESEM, HRTEM, EDX, XRD, TGA, FTIR, and HPLC methods.Results: DLS study has shown the size of SF/5FU-CS and SF/5FU-CS-FA nanoparticles were about 78±14 nm and 142±25 nm, respectively. HRTEM and FESEM studies confirmed the spherical shape with size of 60-70nm for SF/5FU-CS and 90-150 nm for SF/5FU-CS-FA NPs. The XRD results indicated the drug loading and folate-coating comfirmation. FTIR peaks confirmed the presence of drugs in the nanoparticles, as well as folate-coating on the surface of the nanoparticles. TGA results demonstrated the thermostability of both nanoparticles. The release profiles of SF and 5FU from the two designed NPs were found to be in a sustained manner according to the pseudo-second-order kinetics model indicating a good delivery system for tumor cells. The cytotoxicity studies confirmed the better anti-cancer activity of the nanoparticles compared to the free 5-fluorouracil and sorafenib against liver cancer cells, HepG2 and colon cancer cells, HT29. Conversely, both NPs were found not toxic towards normal human dermal fibroblast cells (HDF) cells.

scholarly journals Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 204
Author(s):  
Xiaoyi Gao ◽  
Nan Liu ◽  
Zengming Wang ◽  
Jing Gao ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Chitosan Nanoparticles ◽  
Vaccine Delivery ◽  
Lavage Fluid ◽  
In Vivo Studies ◽  
Modified Chitosan ◽  
Chitosan Nanoparticle ◽  
Low Toxicity ◽  
Intranasal Vaccine

Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.

scholarly journals Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Muhammad H. Sultan ◽  
Sivakumar S. Moni ◽  
Osama A. Madkhali ◽  
Mohammed Ali Bakkari ◽  
Saeed Alshahrani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Human Breast Cancer ◽  
Chromatin Condensation ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Human Breast ◽  
Cytotoxicity Studies ◽  
Mcf 7

AbstractThe present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R2 = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R2 = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

scholarly journals Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy

2020 ◽  
Vol 31 (10) ◽  
pp. 2292-2311
Author(s):  
Adam C. Midgley ◽  
Yongzhen Wei ◽  
Dashuai Zhu ◽  
Fangli Gao ◽  
Hongyu Yan ◽  
...  
Keyword(s):  
Mouse Models ◽  
Plasmid Dna ◽  
Ureteral Obstruction ◽  
Chitosan Nanoparticles ◽  
Unilateral Ureteral Obstruction ◽  
Cellular Growth ◽  
Cell Phenotype ◽  
Targeted Prevention

BackgroundProgressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype.MethodsWe focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)–NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD.ResultsSynthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which—following endocytosis driven by CD44+ cells—promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%–45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition.ConclusionsNanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.

Evaluation of biocompatibility and efficiency of plasmid DNA delivery by gene-activated hydrogels in vitro

2019 ◽  
Vol XIV (2) ◽  
Author(s):  
I.Y. Bozo ◽  
A.A. Titova ◽  
M.N. Zhuravleva ◽  
A.I. Bilyalov ◽  
M.O. Mavlikeev ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Dna Delivery

Formulation of Modified Release Atorvastatin Nanoparticles by Emulsion Interfacial Reaction Method

2015 ◽  
Vol 8 (3) ◽  
pp. 2937-2940
Author(s):  
Sudhakar Sekar ◽  
Shee Sim May
Keyword(s):  
Interfacial Reaction ◽  
Therapeutic Potential ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Morphological Characteristics ◽  
Preparation Technique ◽  
Modified Release ◽  
Reaction Method ◽  
Vitro Release

The aim of the study is to formulate a modified release chitosan nanoparticles for the oral delivery of atorvastatin and to study the in vitro release of atorvastatin from chitosan nanoparticles. Atorvastatin-loaded chitosan nanoparticles were prepared with different concentration of cross-linking agent (glutaraldehyde) by emulsion interfacial reaction method. The formed nanoparticles were characterized in terms of size and morphological characteristics by scanning electron microscopy (SEM) and transmission electron microscope (TEM). Spherical and regular nanoparticles with the size range of 100-250nm were formed. Atorvastatin encapsulation efficiency of nanoparticles was found to be highest in ANP3, followed by ANP2 and ANP1. The in vitro release of atorvastatin was studied by membrane diffusion technique. The resulted cumulative percentage of drug released for ANP1, ANP2 and ANP3 were 60.08%, 34.81% and 20.39% respectively. Through this study, the nanoparticles preparation technique has shown to be a promising approach for enhancing the dissolution of hydrophobic drugs like atorvastatin calcium. The application of this novel delivery system offers good therapeutic potential in the management of hypercholesterolemia and dyslipidemia.

Synthesis and Biological Evaluation of Amoxicillin Loaded Hybrid Material Composite Spheres Against Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 21 ◽  
Author(s):  
Muhammad Arfat Yameen ◽  
Amir Zeb ◽  
Raza E Mustafa ◽  
Sana Mushtaq ◽  
Nargis Aman ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Hybrid Material ◽  
Ag Nanoparticles ◽  
Hybrid Composite ◽  
Synthesis Method ◽  
Biological Evaluation ◽  
Vitro Assay ◽  
Cytotoxicity Studies ◽  
Material Composite

Background: Incoherent use of antibiotics has led toward resistance in MRSA, which is becoming multidrugresistant with high rate of virulence in the community and hospital settings. Objective: Synergistic anti-MRSA activity was investigated in this study for hybrid material composite spheres of amoxicillin, Ag nanoparticles and chitosan which were prepared by one-step synthesis method and various characterizations were performed. Methods: Antimicrobial-susceptibility assay on MRSA was achieved by disc diffusion and agar dilution techniques while agar well diffusion was used for hybrid composite spheres. The in vitro and cytotoxicity studies was done by skin abrasion mouse model and MTT assay on RD cell respectively. Results: All isolates were resistant with the tested antibiotics except vancomycin. MIC against MRSA showed high resistance with amoxicillin from 4 to 128 mg L-1. The mean diameter of chitosan spheres and Ag nanoparticles was 02 mm and 277 nm respectively. Morphology of spheres was uneven, varied, porous and irregular in SEM and Ag nanoparticles presence and formation was also seen in micrograph. No substantial interface among drug, nanoparticles and polymer was found in XRD and IR showed characteristic peaks of all compound in the formulation. The in vitro assay showed augmented anti-MRSA activity with amoxicillin loaded hybrid composite spheres (22-29 mm). A significant reduction in microbial burden (~6.5 log10 CFU ml-1) was seen in vivo with loaded hybrid composite spheres formulation. The MTT assay indicated no potential cytotoxicity with hybrid composite spheres. Conclusion: Synergistic effect, amoxicillin, new hybrid formulation, anti-MRSA activity, composite spheres. nanoparticles.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

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