Polysaccharides as building blocks for nanotherapeutics

Mizrahy, Shoshy; Peer, Dan

doi:10.1039/c1cs15239d

Cited by 373 publications

(286 citation statements)

References 74 publications

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“…Another of those molecules is pullulan, a neutral polymer consisting of α-(1,6)-linked maltotriose residues, which in turn are composed of three glucose molecules connected to each other by an α-(1,4) glycosidic bond (Chiellini et al, 2008;Mizrahy and Peer, 2012;Namazi et al, 2011). Pullulan is produced from starch by the fungus Aureobasidium pullulans and evidences water solubility (Leathers, 2003;Rekha and Chandra, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, the most frequently explored polysaccharide for the design of nanodelivery systems was chitosan, a cationic polymer composed of repeating β-(1,4)-linked N-acetylglucosamine and D-glucosamine units, which is obtained by chitin deacetylation and assumes different molecular weights and deacetylation degrees (Chiellini et al, 2008;Hassani et al, 2012;Mizrahy and Peer, 2012). Apart from the reported biocompatibility and biodegradability (Dornish et al, 1997;Grenha et al, 2010a;Hirano et al, 1988), the most outstanding properties of chitosan rely on its mucoadhesive character (Lehr et al, 1992) and demonstrated ability to potentiate transmucosal absorption both as molecule (Artursson et al, 1994;Borchard et al, 1996;Portero et al, 2002) and in the form of nanoparticle (Al-Qadi et al, 2012;De Campos et al, 2001;Fernández-Urrusuno et al, 1999a;Prego et al, 2005a;Yamamoto et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Dionísio

Cordeiro

Remuñán‐López

et al. 2013

European Journal of Pharmaceutical Sciences

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Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up.In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Dionísio

Cordeiro

Remuñán‐López

et al. 2013

European Journal of Pharmaceutical Sciences

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“…In our study, HA, a natural polysaccharide that has been demonstrated as one of the most promising biomaterials,10 was utilized to encapsulate DOX and CDDP via electrostatic and chelate interactions with its side carboxyl groups, respectively ( Scheme 1 ). The number‐average molecular weight ( M n ) and polydispersity indices (PDI) of HA determined by gel permeation chromatography (GPC) was 16 060 g mol −1 and 1.7, respectively.…”

Section: Resultsmentioning

confidence: 99%

Self‐Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma

et al. 2018

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Osteosarcoma is one of the most serious bone malignancies with rapid speed of deterioration and low survival rate in children and teenagers. Chemotherapy is an important treatment for osteosarcoma, while the conventional small‐molecule therapeutics exhibit low efficacies and severe side effects in the clinic. Drug‐delivery platforms based on nanotechnology, particularly for self‐stabilized delivery platforms with prolonged blood circulation, enhanced intratumoral accumulation, improved antitumor efficacy, and diminished side effects, may break the deadlock on osteosarcoma chemotherapy. Here, a cisplatin (CDDP)‐crosslinked hyaluronic acid (HA) nanogel (CDDPHANG) is prepared for effective delivery of doxorubicin (DOX) to treat osteosarcoma. Importantly, both DOX and CDDP have led clinically used antitumor drugs, and CDDP acts as a crosslinker and ancillary anticarcinogen to prevent the premature release of DOX and to achieve synergistic therapeutic performance. Because of the enhanced stability of the nanogel, this CDDP‐crosslinked DOX‐loaded nanomedicine (CDDPHANG/DOX) exhibits an obviously prolonged circulation time compared to free drugs. Moreover, after valid tumor accumulation, DOX and CDDP are synergistically delivered into the tumor cells and synchronously released into the intracellular acidic environment. Based on the synergistic apoptosis‐inducing effects of DOX and CDDP, CDDPHANG/DOX reveals an evidently enhanced antitumor efficacy compared to free drugs and their combination, indicating its great prospects for the chemotherapy of osteosarcoma.

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“…Chemically, this polymer consists of a-(1,6)-linked maltotriose residues, which in turn are composed of three glucose molecules connected to each other by a-(1,4) glycosidic bonds [6,7]. Several properties have been reported for this material that make it attractive for drug-delivery purposes, including its adhesive ability, as well as the capacity to form fibers and thin biodegradable films [7].…”

Section: Editorialmentioning

confidence: 99%