In Vitro Enzymatic Digestibility of Glutaraldehyde-Crosslinked Chitosan Nanoparticles in Lysozyme Solution and Their Applicability in Pulmonary Drug Delivery

Islam, Nazrul; Wang, Hui; Maqbool, Faheem; Ferro, Vito

doi:10.3390/molecules24071271

Cited by 61 publications

(38 citation statements)

References 47 publications

(85 reference statements)

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“…CHIT degradation is dependent on variations in the distribution of acetamide groups in the chitosan molecule [46]. However, previous reports indicated that CHIT nano/microparticles crosslinked with glutaraldehyde are not degradable in a lysozyme solution [47]. Further, in a review about degradability of chitosan micro/nanoparticles, the authors stated: "To date, no complete in vitro degradation studies of chitosan micro/nanoparticles have been reported, and no degradation data are available in the biological system" [45].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity

et al. 2020

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This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity

et al. 2020

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“…In fact, the higher degree of scaffold degradation (loss of nanofibrous structure) was associated with a higher glucosamine release profile. Independent of drug concentrations in CH scaffolds containing chitosan, without glycosaminoglycans, and loaded with norfloxacin as a free drug, the nanofibrous structure was no longer visible, while CH scaffolds loaded with norfloxacin in nanocomposite were characterized by a nanofibrous structure, partially covered by spherical particles, reported in the literature as lysozyme molecules attached to the biopolymer matrix [36]. The presence of glycosaminoglycans in the scaffolds determined a higher resistance against enzymatic activity.…”

Section: Norfloxacin Release Propertiesmentioning

confidence: 94%

“…Moreover, the presence of montmorillonite in the scaffolds could impair lysozyme activity, probably due to a certain degree of interaction between montmorillonite and chitosan, which could prevent chitosan interaction with the enzyme. Furthermore, the interaction between chitosan and either chondroitin sulfate or hyaluronic acid could render chitosan, as lysozyme substrate, less prone to interaction with lysozyme, resulting in less efficient degradation activity towards chitosan [36].…”

Section: Norfloxacin Release Propertiesmentioning

confidence: 99%

Norfloxacin-Loaded Electrospun Scaffolds: Montmorillonite Nanocomposite vs. Free Drug

et al. 2020

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Infections in nonhealing wounds remain one of the major challenges. Recently, nanomedicine approach seems a valid option to overcome the antibiotic resistance mechanisms. The aim of this study was the development of three types of polysaccharide-based scaffolds (chitosan-based (CH), chitosan/chondroitin sulfate-based (CH/CS), chitosan/hyaluronic acid-based (CH/HA)), as dermal substitutes, to be loaded with norfloxacin, intended for the treatment of infected wounds. The scaffolds have been loaded with norfloxacin as a free drug (N scaffolds) or in montmorillonite nanocomposite (H—hybrid-scaffolds). Chitosan/glycosaminoglycan (chondroitin sulfate or hyaluronic acid) scaffolds were prepared by means of electrospinning with a simple, one-step process. The scaffolds were characterized by 500 nm diameter fibers with homogeneous structures when norfloxacin was loaded as a free drug. On the contrary, the presence of nanocomposite caused a certain degree of surface roughness, with fibers having 1000 nm diameters. The presence of norfloxacin–montmorillonite nanocomposite (1%) caused higher deformability (90–120%) and lower elasticity (5–10 mN/cm2), decreasing the mechanical resistance of the systems. All the scaffolds were proven to be degraded via lysozyme (this should ensure scaffold resorption) and this sustained the drug release (from 50% to 100% in 3 days, depending on system composition), especially when the drug was loaded in the scaffolds as a nanocomposite. Moreover, the scaffolds were able to decrease the bioburden at least 100-fold, proving that drug loading in the scaffolds did not impair the antimicrobial activity of norfloxacin. Chondroitin sulfate and montmorillonite in the scaffolds are proven to possess a synergic performance, enhancing the fibroblast proliferation without impairing norfloxacin’s antimicrobial properties. The scaffold based on chondroitin sulfate, containing 1% norfloxacin in the nanocomposite, demonstrated adequate stiffness to sustain fibroblast proliferation and the capability to sustain antimicrobial properties to prevent/treat nonhealing wound infection during the healing process.

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“…It has been proven that the original high DD of chitosan has fewer linkages between glycosamine and N-acetylglucosamine, which ultimately leads to less combination of hydrogen bonding with the lysozyme following by the changes of the lower flexibility of chitosan chains. In a previous study, the combination of NPs between the chitosan (DD: 92%) and lysozyme has successfully confirmed using glutaraldehyde as a crosslinker, whereas no signs of degradation of immobilized chitosan nanoparticles occurred in lysozyme solution during the incubation period [21]. Based on another study, free lysozyme was also integrated into CS-NPs based on the method of ionic gelation, demonstrating the structure of nanoparticles and the interactions between lysozyme and chitosan nanoparticles through various detection methods [22].…”

Section: Discussionmentioning

confidence: 96%

Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

Wang

Jin

et al. 2020

IJMS

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The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. Lysozyme degrades bacterial cell wall without involving antibiotic resistance and has become a new antibacterial strategy. However, direct use of native, active proteins in clinical settings is not practical as it is fragile under various conditions. In this study, lysozyme was integrated into chitosan nanoparticles (CS-NPs) by the ionic gelation technique to obtain lysozyme immobilized chitosan nanoparticles (Lys-CS-NPs) and then characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which showed a small particle size (243.1 ± 2.1 nm) and positive zeta potential (22.8 ± 0.2 mV). The immobilization significantly enhanced the thermal stability and reusability of lysozyme. In addition, compared with free lysozyme, Lys-CS-NPs exhibited superb antibacterial properties according to the results of killing kinetics in vitro and measurement of the minimum inhibitory concentration (MIC) of CS-NPs and Lys-CS-NPs against Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus). These results suggest that the integration of lysozyme into CS-NPs will create opportunities for the further potential applications of lysozyme as an anti-bacterium agent.

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In Vitro Enzymatic Digestibility of Glutaraldehyde-Crosslinked Chitosan Nanoparticles in Lysozyme Solution and Their Applicability in Pulmonary Drug Delivery

Cited by 61 publications

References 47 publications

RETRACTED: Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity

RETRACTED: Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity

Norfloxacin-Loaded Electrospun Scaffolds: Montmorillonite Nanocomposite vs. Free Drug

Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

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