Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium

Okamoto, Yoshiharu; Watanabe, Midori; Miyatake, K; Morimoto, Minoru; Shigemasa, Yoshihiro; Minami, Saburo

doi:10.1016/s0142-9612(01)00324-6

Cited by 103 publications

(75 citation statements)

References 19 publications

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“…In vitro studies of chitin and chitosan have yielded diverse results: stimulatory [18] and inhibitory [19,20] effects on human cells as well as no influence [21,22] were reported so far. This contradictory outcome appears at least in part to derive from the different chemical compositions and physical forms of the chitosan samples investigated.…”

Section: Discussionmentioning

confidence: 99%

Molecular-Weight-Dependent Toxic Effects of Chitosans on the Human Keratinocyte Cell Line HaCaT

Wiegand

Winter

Hipler

2010

Skin Pharmacol Physiol

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The cationic polysaccharide chitosan possesses bioactive properties such as antimicrobial activity, antitumor effects, hemostatic assets and positive effects on wound healing. The influence of polycations like chitosan on human cells has been reported to depend on their molecular weight. However, the mechanism of cytotoxicity caused by polycations is not yet fully understood. In the study presented, the influence of two chitosans with a similar degree of deacetylation but different molecular weight, chitosan 1130 (120 kDa) and chitosan oligosaccharide (5 kDa), on the human keratinocyte cell line HaCaT was analyzed. The results obtained indicate that chitosans exhibit a molecular-weight-dependent negative effect on HaCaT cell viability and proliferation in vitro. The chitosans tested also stimulated the release of inflammatory cytokines by HaCaT cells depending on incubation time and concentration. Chitosan 1130 and chitosan oligosaccharide induced apoptotic cell death which was mediated by activation of the effector caspases 3/7. At least for chitosan 1130, the involvement of both, extrinsic and intrinsic signal pathways, was shown by activation of caspases 8 and 9.

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Section: Discussionmentioning

confidence: 99%

Molecular-Weight-Dependent Toxic Effects of Chitosans on the Human Keratinocyte Cell Line HaCaT

Wiegand

Winter

Hipler

2010

Skin Pharmacol Physiol

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“…13D & E, respectively) did not enhance the antimigratory activity of ranibizumab opposing the enhanced anti-angiogenic effect obtained in the capillary-like tubule formation assay (Section 3.7.2.2). The anti-migratory activity of chitosan is not yet fully understood, with studies reporting both pro-and inhibitory effects on cell migration (23,108,109) . However, the difference in the anti-angiogenic activity between the two assays may be due to two reasons.…”

Section: (B)mentioning

confidence: 99%

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

et al. 2016

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Age-related macular degeneration (AMD) is the leading cause of certified vision loss worldwide. The standard treatment for neovascular AMD involves repeated intravitreal injections of therapeutic proteins directed against vascular endothelial growth factor, such as ranibizumab. Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), form delivery vehicles which can be used to treat posterior segment eye diseases, but suffer from poor protein loading and release. This work describes a 'system-within-system', PLGA microparticles incorporating chitosan-based nanoparticles, for improved loading and sustained intravitreal delivery of ranibizumab. Chitosan-N-acetyl-L-cysteine (CNAC) was synthesized and its synthesis confirmed using FT-IR and 1 H NMR. Chitosan-based nanoparticles comprised of CNAC, CNAC/tripolyphosphate (CNAC/TPP), chitosan, chitosan/TPP (chit/TPP) or chit/TPP-hyaluronic acid (chit/TPP-HA) were incorporated in PLGA microparticles using a modified w/o/w double emulsion method. Nanoparticles and final nanoparticles-within-microparticles were characterized for their protein-nanoparticle interaction, size, zeta potential, morphology, protein loading, stability, in vitro release, in vivo anti-angiogenic activity and effects on cell viability. The prepared nanoparticles were 17 -350 nm in size and had zeta potentials of -1.4 to +12 mV. Microscopic imaging revealed spherical nanoparticles on the surface of PLGA microparticles for preparations containing chit/TPP, CNAC and CNAC/TPP. Ranibizumab entrapment efficiency in the preparations varied between 13 -69% and was highest for the PLGA microparticles containing CNAC nanoparticles. This preparation also showed the slowest release with no initial burst release compared to all other preparations. Incorporation of TPP to this formulation increased the rate of protein release and reduced entrapment efficiency. PLGA microparticles containing chit/TPP-HA showed the fastest and near-complete release of ranibizumab. All of the prepared empty particles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Ranibizumab released from all preparations maintained its structural integrity and in vitro activity. The chit/TPP-HA preparation enhanced anti-angiogenic activity and may provide a potential biocompatible platform for enhanced anti-angiogenic activity in combination with ranibizumab. In conclusion, the PLGA microparticles containing CNAC nanoparticles, showed significantly improved ranibizumab loading and release profile. This novel drug delivery system may have potential for improved intravitreal delivery of therapeutic proteins, thereby reducing the frequency, risk and cost of burdensome intravitreal injections.

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“…Estudos realizados por Okamoto 47 sugerem que o principal efeito analgésico da quitosana é decorrente da captura de hidrogênios ácidos liberados no local da inflamação pela ionização do grupo amínico a NH 3 + . A bradicinina, mediador químico liberado pelo cininogênio plasmático e outras citocinas, como Fator de Necrose Tumoral α (FNTα) e as Interleucinas 1 (IL-1) e 8 (IL-8), parece ser particularmente importante para a produção da dor no local inflamado 48 .…”

Section: Efeito Analgésicounclassified

Quitosana: derivados hidrossolúveis, aplicações farmacêuticas e avanços

Silva¹,

Santos²,

Ferreira³

2006

Quím. Nova

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Recebido em 15/3/05; aceito em 3/8/05; publicado na web em 14/3/06 CHITOSAN: HYDROSSOLUBLE DERIVATIVES, PHARMACEUTICAL APPLICATIONS AND RECENT ADVANCES. Chitin and chitosan are copolymers build from N-acetyl-D-glucosamine and D-glucosamine. The former is widely found in nature and yields the latter on deacetylation. The copolymers are being used for several purposes. Since 1977, when the First International Conference on Chitin and Chitosan was held in Boston, USA, the interest on chitin and chitosan has remarkably increased. This review emphasizes pharmaceutical applications of chitosan and its derivatives, and presents recent advances. Some therapeutical applications of these polymers are also discussed.Keywords: chitosan; hydrossoluble derivatives; pharmaceutical applications. INTRODUÇÃOQuitina e quitosana são copolímeros constituídos por unidades Nacetil-D-glicosamina e D-glicosamina em proporções variáveis, sendo que o primeiro tipo dessas unidades predomina no caso de quitina, enquanto quitosana é composta predominantemente, por unidades Dglicosamina 1 . A quitina é o segundo polissacarídeo mais abundante na natureza depois da celulose, sendo o principal componente do exoesqueleto de crustáceos e insetos; sua presença ocorre também em nematóides e parede celular de fungos e leveduras 1 . A quitosana pode ser obtida a partir da quitina por meio da desacetilação com álcalis, podendo também estar naturalmente presente em alguns fungos, como aqueles pertecentes aos gêneros Mucor e Zygomicetes 2 . De acordo com o grau médio de acetilação (GA), parâmetro empregado para caracterizar o conteudo médio de unidades N-acetil-D-glicosamina de quitina e quitosana, podem-se obter diversas quitosanas variando-se, assim, suas propriedades físico-químicas, como solubilidade, pKa e viscosidade 3 . Geralmente, é difícil de se obter quitosana com elevado grau de desacetilação, pois, à medida que este aumenta, a possibilidade de degradação do polímero também aumenta 4 . A Figura 1 representa as estruturas químicas parciais da quitina e quitosana.O emprego de quitina e quitosana e a pesquisa por novas aplicações têm aumentado exponencialmente em diversas áreas, como na agricultura e indústria de alimentos, mas, especialmente, na indústria farmacêutica, no desenvolvimento de cosméticos 5-12 e biomateriais, tais como géis, filmes e membranas poliméricas [13][14][15][16][17] . De acordo com Khor 18 , um aspecto importante na utilização de quitosana diz respeito à sua produção a partir da quitina. Esta deve ser realizada de forma adequada, de maneira que garanta, ao final do processo, a obtenção de quitosana com alto grau de pureza, sobretudo isenta de contaminantes, como proteínas, endotoxinas e metais tóxicos. Neste âmbito, é válido ressaltar que o polímero obtido deve ser caracterizado adequadamente quanto à massa molar, grau de acetilação e distribuição deste grupo ao longo da cadeia polimérica. Estas características podem influenciar na biodegradabilidade do mesmo, principalmente na acessibilidade enzimática, influenciando a hi...

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Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium

Cited by 103 publications

References 19 publications

Molecular-Weight-Dependent Toxic Effects of Chitosans on the Human Keratinocyte Cell Line HaCaT

Molecular-Weight-Dependent Toxic Effects of Chitosans on the Human Keratinocyte Cell Line HaCaT

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

Quitosana: derivados hidrossolúveis, aplicações farmacêuticas e avanços

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