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Development of Alginate/Chitosan Microparticles for Dust Mite Allerge
T Suksamran, P Opanasopit, T Rojanarata, T Ngawhirunpat
Tropical Journal of Pharmaceutical Research , 2011,
Abstract: Purpose: To develop chitosan/alginate microparticles for the mucosal delivery of allergen from dust mite (Dermatophagoides pteronyssinus). Methods: Chitosan/alginate microparticles were prepared by ionotropic gelation. The effects of polymer content, crosslinking agent, and preparation method on the physicochemical characteristics of the microparticles as well as their in vitro cytotoxicity were investigated. Results: The microparticles were small (1 - 17 μm) and spherical in shape. The highest allergen content (0.30 ± 0.07 mg/g) was obtained with 2.5 % initial allergen loading in chitosan- triphosphate (CS-TPP) microparticles. Sustained allergen release (approx. 50 % over 24 h) was observed from alginate-coated chitosan microparticles. Allergen incorporation method and initial drug-loading could be varied to obtain optimum particle size with high allergen-loading and sustained release. The cytotoxicity of various microparticle formulations did not differ significantly (p > 0.05 ), as cell viability values were close to 100 %. Conclusion: This study indicates that alginate and alginate-coated chitosan microparticles are safe and can be further developed for mucosal allergen delivery.
Application in the Ethanol Fermentation of Immobilized Yeast Cells in Matrix of Alginate/Magnetic Nanoparticles, on Chitosan-Magnetite Microparticles and Cellulose-coated Magnetic Nanoparticles  [PDF]
Viara Ivanova,Petia Petrova,Jordan Hristov
Quantitative Biology , 2011,
Abstract: Saccharomyces cerevisiae cells were entrapped in matrix of alginate and magnetic nanoparticles and covalently immobilized on magnetite-containing chitosan and cellulose-coated magnetic nanoparticles. Cellulose-coated magnetic nanoparticles with covalently immobilized thermostable {\alpha}-amylase and chitosan particles with immobilized glucoamylase were also prepared. The immobilized cells and enzymes were applied in column reactors - 1/for simultaneous corn starch saccharification with the immobilized glucoamylase and production of ethanol with the entrapped or covalently immobilized yeast cells, 2/ for separate ethanol fermentation of the starch hydrolysates with the fixed yeasts. Hydrolysis of corn starch with the immobilized {\alpha}-amylase and glucoamylase, and separate hydrolysis with the immobilized {\alpha}-amylase were also examined. In the first reactor the ethanol yield reached approx. 91% of the theoretical; the yield was approx. 86% in the second. The ethanol fermentation was affected by the type of immobilization, the initial particle loading, feed sugar concentration and the dilution rate. The ethanol productivity with entrapped cells reached 264.0 g/L.h at particle loading rate 70% and dilution rate 3.0 h-1 with reducing sugar concentration of 200.0 g/L. The prepared magnetic particles with fixed yeast cells were stable at 4oC in saline for more than 1 month. .
The effect of chitosan molecular weight on the properties of alginate/ chitosan microparticles containing prednisolone
S Honary, M Maleki, M Karami
Tropical Journal of Pharmaceutical Research , 2009,
Abstract: Purpose: The aim of the present study was to investigate the effect of chitosan molecular weight on size, size distribution, release rate, mucoadhesive properties and electrostatic bonding of alginate/chitosan microparticles containing prednisolone Methods: Three mucoadhesive alginate/chitosan microparticle formulations, f1, f2 and f3, were prepared using low, medium and high chitosan molecular weight (MW) chitosan, respectively, by directly spraying alginate solution into a solution of chitosan and calcium chloride at optimum conditions. Prednisolone was incorporated in the alginate solution prior to spraying. The microparticles were then evaluated for prednisolone content, size, release rate, and mucoadhesive properties using appropriate methods. The formation of electrostatic and hydrogen bonds between chitosan and alginate was assessed by differential scanning calorimetetry (DSC) and Fourier transform infrared (FTIR). Results: The results indicate that high MW chitosan microparticles were significantly (p<0.05) smaller and more uniform in size, with better mucoadhesive properties and lower release rate than the other formulations. FTIR and DSC studies indicate that stronger hydrogen and electrostatic bonding in the formulation containing high MW chitosan than inthe other formulations Conclusion: The physicochemical properties of chitosan-alginate microparticles are dependent on the molecular weight of chitosan
Enhanced Hemostatic Performance of Tranexamic Acid-Loaded Chitosan/Alginate Composite Microparticles
Donghong Li,Pengxi Li,Jiatao Zang,Jiancang Liu
Journal of Biomedicine and Biotechnology , 2012, DOI: 10.1155/2012/981321
Abstract: Novel microparticles based on chitosan and sodium alginate were prepared using emulsification and cross-linking technologies. The spherical microparticles had a porous surface and a diameter of  m. In simulated body fluid, these microparticles quickly swelled but gradually degraded. The results of the MTT assay revealed that a slight inhibition of cell proliferation was observed on day 2 and then gradually decreased afterward. No cell morphology changes were observed. By loading tranexamic acid, the hemostatic performance of the microparticles was obviously improved. Using fast-acting styptic powder (Flashclot) as the control, the hemostatic efficiency was investigated in rabbits using a liver transection bleeding model. It was found that both Flashclot and the microparticles achieved hemostasis in  min and  min, respectively; however, the tranexamic acid-loaded microparticles stopped the bleeding in  min (). Additionally, Flashclot resulted in heat injury to the experimental livers, while the microparticles did not. Thus, with their biodegradability, safety, and superior hemostatic efficiency, tranexamic acid-loaded microparticles might be a promising new powdered hemostatic agent with a wide range of potential applications.
Dissolution of Curcumin Microencapsulation Coated by Chitosan-Alginate-Glutaraldehide
Herdini,Latifah K. Darusman,Purwantiningsih Sugita
Makara Seri Sains , 2010,
Abstract: In vitro dissolution of curcumin coated by chitosan-alginate gel in its optimum condition was studied. The maceration process using 17.08% ethanol yields and the content of the curcumin in the extract detected by visible spectrophotometry 430 nm is found to be 10.30%. its optimum condition was obtained using response surface method at concentration was fixed (1.75% [b/v]). The dissolution assay was done at 37 C, at 100 rpm of stirring rate in 8 hours. Aliquots were taken at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480 minutes. Absorbance of the Aliquots was measured at 430 nm. The curcumin released has the best linear correlation to the first order reaction with releasesd constant, k = 2.24 10-3 minute-1 while it’s half live is t1/2 = 5.16 hours. Release curcumin was determined mainly by diffusion mechanism. Compared to the result based on Fick model, the one of Higuchi model is better in agreement in reproducing the released data.
Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats
Li X, Qi J, Xie Y, Zhang X, Hu S, Xu Y, Lu Y, Wu W
International Journal of Nanomedicine , 2013, DOI: http://dx.doi.org/10.2147/IJN.S38507
Abstract: noemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats Original Research (2056) Total Article Views Authors: Li X, Qi J, Xie Y, Zhang X, Hu S, Xu Y, Lu Y, Wu W Published Date December 2012 Volume 2013:8 Pages 23 - 32 DOI: http://dx.doi.org/10.2147/IJN.S38507 Received: 25 September 2012 Accepted: 27 October 2012 Published: 28 December 2012 Xiaoyang Li, Jianping Qi, Yunchang Xie, Xi Zhang, Shunwen Hu, Ying Xu, Yi Lu, Wei Wu Key Laboratory of Smart Drug Delivery of Ministry of Education and People's Liberation Army (PLA), School of Pharmacy, Fudan University, Shanghai, China Abstract: This study aimed to prepare nanoemulsions coated with alginate/chitosan for oral insulin delivery. Uncoated nanoemulsions were prepared by homogenization of a water in oil in water (w/o/w) multiple emulsion that was composed of Labrafac CC, phospholipid, Span 80 and Cremorphor EL. Coating of the nanoemulsions was achieved based on polyelectrolyte cross-linking, with sequential addition of calcium chloride and chitosan to the bulk nanoemulsion dispersion that contained alginate. The particle size of the coated nanoemulsions was about 488 nm and the insulin entrapment ratio was 47.3%. Circular dichroism spectroscopy proved conformational stability of insulin against the preparative stress. In vitro leakage study indicated well-preserved integrity of the nanoemulsions in simulated gastric juices. Hypoglycemic effects were observed in both normal and diabetic rats. The relative pharmacological bioavailability of the coated nanoemulsion with 25 and 50 IU/kg insulin were 8.42% and 5.72% in normal rats and 8.19% and 7.84% in diabetic rats, respectively. Moreover, there were significantly prolonged hypoglycemic effects after oral administration of the coated nanoemulsions compared with subcutaneous (sc) insulin. In conclusion, the nanoemulsion coated with alginate/chitosan was a potential delivery system for oral delivery of polypeptides and proteins.
Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats  [cached]
Li X,Qi J,Xie Y,Zhang X
International Journal of Nanomedicine , 2012,
Abstract: Xiaoyang Li, Jianping Qi, Yunchang Xie, Xi Zhang, Shunwen Hu, Ying Xu, Yi Lu, Wei WuKey Laboratory of Smart Drug Delivery of Ministry of Education and People's Liberation Army (PLA), School of Pharmacy, Fudan University, Shanghai, ChinaAbstract: This study aimed to prepare nanoemulsions coated with alginate/chitosan for oral insulin delivery. Uncoated nanoemulsions were prepared by homogenization of a water in oil in water (w/o/w) multiple emulsion that was composed of Labrafac CC, phospholipid, Span 80 and Cremorphor EL. Coating of the nanoemulsions was achieved based on polyelectrolyte cross-linking, with sequential addition of calcium chloride and chitosan to the bulk nanoemulsion dispersion that contained alginate. The particle size of the coated nanoemulsions was about 488 nm and the insulin entrapment ratio was 47.3%. Circular dichroism spectroscopy proved conformational stability of insulin against the preparative stress. In vitro leakage study indicated well-preserved integrity of the nanoemulsions in simulated gastric juices. Hypoglycemic effects were observed in both normal and diabetic rats. The relative pharmacological bioavailability of the coated nanoemulsion with 25 and 50 IU/kg insulin were 8.42% and 5.72% in normal rats and 8.19% and 7.84% in diabetic rats, respectively. Moreover, there were significantly prolonged hypoglycemic effects after oral administration of the coated nanoemulsions compared with subcutaneous (sc) insulin. In conclusion, the nanoemulsion coated with alginate/chitosan was a potential delivery system for oral delivery of polypeptides and proteins.Keywords: insulin, oral delivery, alginate, chitosan, nanoemulsion
Pharmacokinetic Evaluation of Chitosan-Succinyl-Prednisolone Conjugate Microparticles as a Colonic Delivery System: Comparison with Enteric-Coated Conjugate Microparticles  [PDF]
Hiraku Onishi
Health (Health) , 2014, DOI: 10.4236/health.2014.611157
Abstract: In the previous study, chitosan-succinyl-prednisolone conjugate microparticles (MP) were found to exhibit good efficacy and reduced toxicity nearly as well as their Eudragit L-coated microparticles (MP/EuL). This proposes a question whether enteric-coating of MP is necessary or not. Although MP/EuL were already examined for their pharmacokinetic and gastrointestinal behaviors, MP have not been done yet. Therefore, in this study, MP were evaluated by investigating pharmacokinetic features in detail. MP with the in vitro features equivalent to those of the previous conjugate microparticles could be produced more readily in the modified preparative method. Pharmacokinetic and gastrointestinal behaviors of MP were investigated by intragastric dosing (5 mg PD eq./kg) to rats with 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis. The plasma concentration was suppressed extensively in MP as well as MP/EuL, supporting the reduction of PD systemic toxic side effects. However, the plasma level increased gradually up to 7 h in MP, but not in MP/EuL. At 8 h after dosing, MP were detected in the stomach to a fair extent, and free PD was found there, indicating that MP were subjected to trapping in the stomach probably due to positive charge of chitosan molecules. For MP, such prolonged localization and slow release of PD in the stomach were probably associated with the gradual increase in plasma concentration. Therefore, MP/EuL were evaluated to be superior to MP for effective targeting to ulcerative colitis. It is concluded that enteric-coating is very important for the targeting system using MP.
A New Strategy Based on Smrho Protein Loaded Chitosan Nanoparticles as a Candidate Oral Vaccine against Schistosomiasis  [PDF]
Carolina R. Oliveira ,Cíntia M. F. Rezende,Marina R. Silva,Ana Paula Pêgo,Olga Borges,Alfredo M. Goes
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001894
Abstract: Background Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. Methods and Findings Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. Conclusions Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.
Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice  [PDF]
Ze Liu, Dan Lv, Shu Liu, Junbo Gong, Da Wang, Min Xiong, Xiaoniao Chen, Rong Xiang, Xiaoyue Tan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060190
Abstract: Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs). Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer’s patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3+/CD8+/CD25+) when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.
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