How the Lack of Chitosan Characterization Precludes Implementation of the Safe-by-Design Concept

Marques, Cíntia; Som, Claudia; Schmutz, Mélanie; Borges, Olga; Borchard, Gerrit

doi:10.3389/fbioe.2020.00165

Cited by 41 publications

(22 citation statements)

References 95 publications

(157 reference statements)

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“…CS has been extensively investigated as a mucoadhesive drug nanocarrier, and its cytotoxicity is a matter of debate [ 35 , 36 ], including for i.n. drug delivery [ 37 , 38 , 39 , 40 ]. Most works reported on the good cell compatibility of this polysaccharide that is classified as “generally recognized as safe” (GRAS) by the US Food and Drug Administration (FDA) [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

2020

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Intranasal (i.n.) administration became an alternative strategy to bypass the blood–brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1 h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall, results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions, and thus, they could be beneficial in the treatment of different medical conditions.

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Section: Introductionmentioning

confidence: 99%

Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

2020

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“…While some authors claim that low MW chitosan (10 kDa) is more effective in immune system stimulation than high MW chitosan (300 kDa) [88], others show that MW around 300 kDa has a greater immunostimulatory effect than a low MW [89]. Furthermore, different sources of γ-PGA can strongly impact the host immune response [90] as well as Ch sources [91]. Thus, the advances on this area can undergo to the standardization of nanoformulation composition, ensuring the reproducibility of the preparation to obtain the desired biological effect.…”

Section: Discussionmentioning

confidence: 99%

Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer

et al. 2020

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Over the years, researchers paid attention to establish strategies for improving efficacy and safety of the nanomaterials. Recently, researchers introduced 'Safe-by-Design' approach as a strategy for the development of safe and effective nanomaterials [194][195][196][197]. The purpose of 'Safe-by-Design' approach is to assess the safety of the nanomaterials from its early stage of innovation process, reduce Figure 13.…”

Section: Clinical Studies Of Nano-drug Delivery Systemsmentioning

confidence: 99%

Multifunctional and stimuli-responsive nanocarriers for targeted therapeutic delivery

Majumder

Minko

2020

Expert Opinion on Drug Delivery

118

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Introduction: Nanocarrier-based delivery systems offer multiple benefits to overcome limitations of the traditional drug dosage forms, such as protection of the drug, enhanced bioavailability, targeted delivery to disease site, etc. Nanocarriers have exhibited tremendous successes in targeted delivery of therapeutics to the desired tissues and cells with improved bioavailability, high drug loading capacity, enhanced intracellular delivery, and better therapeutic effect. A specific design of stimuli-responsive nanocarriers allows for changing their structural and physicochemical properties in response to exogenous and endogenous stimuli. These nanocarriers show a promise in site specific controlled release of therapeutics under certain physiological conditions or external stimuli. Areas covered: This review highlights recent progresses on the multifunctional and stimuli-sensitive nanocarriers for targeted therapeutic drug delivery applications. Expert opinion: The progress from single functional to multifunctional nanocarriers has shown tremendous potential for targeted delivery of therapeutics. On our opinion, the future of targeted delivery of drugs, nucleic acids, and other substances belongs to the site-targeted multifunctional and stimulibased nanoparticles with controlled release. Targeting of nanocarriers to the disease site enhance the efficacy of the treatment by delivering more therapeutics specifically to the affected cells and substantially limiting adverse side effects upon healthy organs, tissues, and cells.

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How the Lack of Chitosan Characterization Precludes Implementation of the Safe-by-Design Concept

Cited by 41 publications

References 95 publications

Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer

Multifunctional and stimuli-responsive nanocarriers for targeted therapeutic delivery

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