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Water-soluble chitosan nanoparticles as a novel carrier system for protein delivery
Chun Wang,Xiong Fu,LianSheng Yang
Chinese Science Bulletin , 2007, DOI: 10.1007/s11434-007-0127-y
Abstract: High MW chitosan (CS) solutions have already been proposed as vehicles for protein delivery. The aim of the present work is to investigate the potential utility of water-soluble chitosan (WSC) as vehicles to load and deliver proteins. WSC nanoparticles (WSC NP) with various formations were prepared based on ionic gelation of WSC with pentasodium tripolyphosphate (TPP) anions. Bovine serum albumin (BSA) was used as a model protein drug incorporated into the WSC nanoparticles. Blank and BSA-loaded WSC nanoparticles were examined and determined to have a spherical shape with diameters between 35–190 nm, and zeta potential between 35–42 mV. FTIR confirmed that the tripolyphosphoric groups of TPP linked to the ammonium groups of WSC in the nanoparticles. Some factors affecting delivery properties of BSA have been investigated. Altering the concentration of BSA from 0.05 to 1 mg/mL enhanced the loading capacity of BSA but decreased loading efficiency simultaneously. Also, with the introduction of poly ethylene glycol (PEG), BSA release accelerated. Nanoparticle preparation from WSC with various deacetylation degrees (DDs) from 72.6% to 90% and MWs ranging from 3.5 to 15.8 kDa promoted loading efficiency and decreased the release rate. These results indicate that WSC nanoparticles are promising carriers for protein delivery.
Water-soluble chitosan nanoparticles as a novel carrier system for protein delivery
Wang Chun Fu Xiong Yang Liansheng,
WANG
,Chun,FU,Xiong,YANG,LianSheng

科学通报(英文版) , 2007,
Abstract: High MW chitosan (CS) solutions have already been proposed as vehicles for protein delivery. The aim of the present work is to investigate the potential utility of water-soluble chitosan (WSC) as vehicles to load and deliver proteins. WSC nanoparticles (WSC NP) with various formations were prepared based on ionic gelation of WSC with pentasodium tripolyphosphate (TPP) anions. Bovine serum albumin (BSA) was used as a model protein drug incorporated into the WSC nanoparticles. Blank and BSA-loaded WSC nanoparticles were examined and determined to have a spherical shape with diameters between 35–190 nm, and zeta potential between 35–42 mV. FTIR confirmed that the tripolyphosphoric groups of TPP linked to the ammonium groups of WSC in the nanoparticles. Some factors affecting delivery properties of BSA have been investigated. Altering the concentration of BSA from 0.05 to 1 mg/mL enhanced the loading capacity of BSA but decreased loading efficiency simultaneously. Also, with the introduction of poly ethylene glycol (PEG), BSA release accelerated. Nanoparticle preparation from WSC with various deacetylation degrees (DDs) from 72.6% to 90% and MWs ranging from 3.5 to 15.8 kDa promoted loading efficiency and decreased the release rate. These results indicate that WSC nanoparticles are promising carriers for protein delivery.
Chitosan–Pluronic nanoparticles as oral delivery of anticancer gemcitabine: preparation and in vitro study
Hosseinzadeh H, Atyabi F, Dinarvand R, Ostad SN
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S26365
Abstract: osan–Pluronic nanoparticles as oral delivery of anticancer gemcitabine: preparation and in vitro study Original Research (4458) Total Article Views Authors: Hosseinzadeh H, Atyabi F, Dinarvand R, Ostad SN Published Date April 2012 Volume 2012:7 Pages 1851 - 1863 DOI: http://dx.doi.org/10.2147/IJN.S26365 Received: 21 September 2011 Accepted: 17 December 2011 Published: 11 April 2012 Hosniyeh Hosseinzadeh1, Fatemeh Atyabi1, Rassoul Dinarvand1, Seyed Naser Ostad2 1Nanotechnology Research Centre, 2Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Abstract: Nanoparticles have proven to be an effective delivery system with few side effects for anticancer drugs. In this study, gemcitabine-loaded nanoparticles have been prepared by an ionic gelation method using chitosan and Pluronic F-127 as a carrier. Prepared nanoparticles were characterized using dynamic light scattering, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy, and transmission electron microscopy. Different parameters such as concentration of sodium tripolyphosphate, chitosan, Pluronic, and drug on the properties of the prepared nanoparticles were evaluated. In vitro drug release was studied in phosphate-buffered saline (PBS; pH = 7.4). The cytotoxicity of the nanoparticles was assayed in the HT-29 colon cancer cell line. The mucoadhesion behavior of the nanoparticles was also studied by mucus glycoprotein assay. The prepared nanoparticles had a spherical shape with positive charge and a mean diameter ranging between 80 to 170 nm. FT-IR and DSC studies found that the drug was dispersed in its amorphous form due to its potent interaction with nanoparticle matrix. Maximum drug encapsulation efficiency was achieved at 0.4 mg/mL gemcitabine while maximum drug loading was 6% obtained from 0.6 mg/mL gemcitabine. An in vitro drug release study at 37°C in PBS (pH = 7.4) exhibited a controlled release profile for chitosan–Pluronic F-127 nanoparticles. A cytotoxicity assay of gemcitabine-loaded nanoparticles showed an increase in the cytotoxicity of gemcitabine embedded in the nanoparticles in comparison with drug alone. The mucoadhesion study results suggest that nanoparticles could be considered as an efficient oral formulation for colon cancer treatment.
Preparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery
Yuan H, Bao X, Du YZ, You J, Hu FQ
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S35575
Abstract: eparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery Original Research (1752) Total Article Views Authors: Yuan H, Bao X, Du YZ, You J, Hu FQ Published Date September 2012 Volume 2012:7 Pages 5119 - 5128 DOI: http://dx.doi.org/10.2147/IJN.S35575 Received: 03 July 2012 Accepted: 08 August 2012 Published: 26 September 2012 Hong Yuan, Xin Bao, Yong-Zhong Du, Jian You, Fu-Qiang Hu College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China Purpose: Both polymer micelles and mesoporous silica nanoparticles have been widely researched as vectors for small molecular insoluble drugs. To combine the advantages of copolymers and silica, studies on the preparation of copolymer-silica composites and cellular evaluation were carried out. Methods: First, a stearic acid-g-chitosan (CS-SA) copolymer was synthesized through a coupling reaction, and then silicone oxide (SiO2)-deposited doxorubicin (DOX)-loaded stearic acid-g-chitosan (CS-SA/SiO2/DOX) nanoparticles were prepared through the sol-gel reaction. Physical and chemical properties such as particle size, zeta potential, and morphologies were examined, and small-angle X-ray scattering (SAXS) analysis was employed to identify the mesoporous structures of the generated nanoparticles. Cellular uptake and cytotoxicity studies were also conducted. Results: CS-SA/SiO2/DOX nanoparticles with different amounts of SiO2 deposited were obtained, and SAXS studies showed that mesoporous structures existed in the CS-SA/SiO2/DOX nanoparticles. The mesoporous size of middle-ratio and high-ratio deposited CS-SA/SiO2/DOX nanoparticles were 4–5 nm and 8–10 nm, respectively. Based on transmission electron microscopy images of CS-SA/SiO2/DOX nanoparticles, dark rings around the nanoparticles could be observed in contrast with CS-SA/DOX micelles. Furthermore, CS-SA/SiO2/DOX nanoparticles exhibited faster release behavior in vitro than CS-SA/DOX micelles; cellular uptake research in A549 indicated that the CS-SA/SiO2/DOX nanoparticles were taken up by A549 cells more rapidly, and that CS-SA/SiO2/DOX nanoparticles entered the cell more easily when the amount of SiO2 was higher. IC50 values of CS-SA/DOX micelles, CS-SA/SiO2/DOX-4, CS-SA/SiO2/DOX-8, and CS-SA/SiO2/DOX-16 nanoparticles against A549 cells measured using the MTT assay were 1.69, 0.93, 0.32, and 0.12 μg/mL, respectively. Conclusion: SiO2-deposited stearic acid-g-chitosan organic–inorganic composites show promise as nanocarriers for hydrophobic drugs such as DOX.
Antifungal Activity of Chitosan Nanoparticles and Correlation with Their Physical Properties  [PDF]
Ling Yien Ing,Noraziah Mohamad Zin,Atif Sarwar,Haliza Katas
International Journal of Biomaterials , 2012, DOI: 10.1155/2012/632698
Abstract: The need of natural antimicrobials is paramount to avoid harmful synthetic chemicals. The study aimed to determine the antifungal activity of natural compound chitosan and its nanoparticles forms against Candida albicans, Fusarium solani and Aspergillus niger. Chitosan nanoparticles were prepared from low (LMW), high molecular weight (HMW) chitosan and its derivative, trimethyl chitosan (TMC). Particle size was increased when chitosan/TMC concentration was increased from 1 to 3 mg/mL. Their zeta potential ranged from +22 to +55?mV. Chitosan nanoparticles prepared from different concentrations of LMW and HMW were also found to serve a better inhibitory activity against C. albicans ( –0.86?mg/mL and –1.0?mg/mL) and F. solani ( –1.2?mg/mL and –1.2?mg/mL) compared to the solution form ( ?mg/mL for both MWs and species). This inhibitory effect was also influenced by particle size and zeta potential of chitosan nanoparticles. Besides, Aspergillus niger was found to be resistant to chitosan nanoparticles except for nanoparticles prepared from higher concentrations of HMW. Antifungal activity of nanoparticles prepared from TMC was negligible. The parent compound therefore could be formulated and applied as a natural antifungal agent into nanoparticles form to enhance its antifungal activity. 1. Introduction For the past few decades, there has been a growing interest in the modification and application of chitosan in medical and health fields. Chitosan has been the material of choice for the preparation of nanoparticles in various applications due to its biodegradable and nontoxic properties. Chitosan is soluble in acidic condition and the free amino groups on its polymeric chains protonates and contributes to its positive charge [1]. Chitosan nanoparticles are formed spontaneously on the incorporation of polyanion such as tripolyphosphate (TPP) in chitosan solution under continuous stirring condition. These nanoparticles are then harvested and used for gene therapy and drug delivery applications [2, 3]. However, due to its poor solubility at pH above 6.5, various chitosan derivatives with enhanced water solubility are introduced through chemical modification process, for example, N-trimethyl chitosan (TMC). Chitosan in its free polymer form has been proved to have antifungal activity against Aspergillus niger, Alternaria alternata, Rhizopus oryzae, Phomopsis asparagi, and Rhizopus stolonifer [4–6]. From these findings, it could be concluded that antifungal activity of chitosan was influenced by its molecular weight, degree of substitution, concentration, types
Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system
Mohammadpour Dounighi, N;Eskandari, R;Avadi, MR;Zolfagharian, H;Mir Mohammad Sadeghi, A;Rezayat, M;
Journal of Venomous Animals and Toxins including Tropical Diseases , 2012, DOI: 10.1590/S1678-91992012000100006
Abstract: hydrophilic nanoparticles have been widely investigated in recent years as delivery systems for therapeutic macromolecules such as antigens. in the present study mesobuthus eupeus venom-loaded chitosan nanoparticles were prepared via ionic gelation of tripolyphosphate (tpp) and chitosan. the optimum encapsulation efficiency (91.1%) and loading capacity (76.3%) were obtained by a chitosan concentration of 2 mg/ml, chitosan-to-tpp mass ratio of 2 and m. eupeus venom concentration of 500 μg/ml. the average nanoparticle size at optimum conditions was determined by zetasizer (malvern instruments, uk). the nanoparticle size was about 370 nm (polydispersity index: 0.429) while the zeta potential was positive. transmission electron microscope (tem) imaging showed a spherical, smooth and almost homogenous structure for nanoparticles. fourier transform infrared (ftir) spectroscopy confirmed tripolyphosphoric groups of tpp linked with ammonium groups of chitosan in the nanoparticles. the in vitro release of nanoparticles showed an initial burst release of approximately 60% in the first ten hours, followed by a slow and much reduced additional release for about 60 hours. it is suggested that the chitosan nanoparticles fabricated in our study may provide a suitable alternative to traditional adjuvant systems.
Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery
Tan Q, Liu WD, Guo CY, Zhai GX
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S22411
Abstract: eparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery Original Research (5672) Total Article Views Authors: Tan Q, Liu WD, Guo CY, Zhai GX Published Date August 2011 Volume 2011:6 Pages 1621 - 1630 DOI: http://dx.doi.org/10.2147/IJN.S22411 Qi Tan1, Weidong Liu1,2, Chenyu Guo1, Guangxi Zhai1 1Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan; 2Department of Pharmacy, Linyi People's Hospital Affiliated to Shandong University, Linyi, People's Republic of China Background: The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods: Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results: Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion: Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin.
Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery  [cached]
Tan Q,Liu WD,Guo CY,Zhai GX
International Journal of Nanomedicine , 2011,
Abstract: Qi Tan1, Weidong Liu1,2, Chenyu Guo1, Guangxi Zhai11Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan; 2Department of Pharmacy, Linyi People's Hospital Affiliated to Shandong University, Linyi, People's Republic of ChinaBackground: The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin.Methods: Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control.Results: Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin.Conclusion: Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin.Keywords: quercetin, tocopheryl polyethylene glycol succinate, lecithin, chitosan, nanoparticles, topical delivery
Preparation and application of chitosan nanoparticles and nanofibers
Zhao, Li-Ming;Shi, Lu-E;Zhang, Zhi-Liang;Chen, Jian-Min;Shi, Dong-Dong;Yang, Jie;Tang, Zhen-Xing;
Brazilian Journal of Chemical Engineering , 2011, DOI: 10.1590/S0104-66322011000300001
Abstract: encapsulation and immobilization technology is important for the food processing and bioengineering industries. chitosan is a natural polysaccharide prepared by the n - deacetylation of chitin. it has been widely used in food and bioengineering industries, including the encapsulation of active food ingredients, in enzyme immobilization, and as a carrier for controlled drug delivery, due to its significant biological and chemical properties such as biodegradability, biocompatibility, bioactivity, and polycationicity. in this work, chitosan nanoparticles and nanofibers used to encapsulate bioactive substances and immobilize enzymes were reviewed. preparation of chitosan nanoparticles and nanofibers, including the work achieved in our group on chitosan nanoparticles for enzyme immobilization, were also introduced. some problems encountered with nano - structured chitosan carriers for bioactive substance encapsulation and enzyme immobilization were discussed, together with the future prospects of such systems.
Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method  [cached]
Zu Y,Zhao Q,Zhao X,Zu S
International Journal of Nanomedicine , 2011,
Abstract: Yuangang Zu, Qi Zhao, Xiuhua Zhao, Shuchong Zu, Li MengKey Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang, ChinaAbstract: Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.Keywords: oligomycin-A, chitosan, folate, targeted drug delivery system, nanoparticles, two-level factorial design
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