Original Article
Antioxidant idebenone-loaded nanoparticles based on chitosan and N-carboxymethylchitosan

https://doi.org/10.1016/j.nano.2010.06.006Get rights and content

Abstract

Nanoparticles based on chitosan (Ch) and N-carboxymethylchitosan (N-CMCh) cross-linked with tripolyphosphate (TPP) were developed by co-drying with idebenone in different polymer-to-drug ratios (1.3:1 to 16:1) with 20% (wt/wt) colloidal silicon dioxide and tripolyphosphate (0.2 mg/mL). At high ratios (8:1 and 16:1) the spray-dried powder showed spherical and dense particles with a size close to 1 μm, allowing almost complete drug coating by the polymeric system and a high efficiency of drug incorporation (>90% and >80%, for Ch and N-CMCh, respectively). The nanoparticles showed a 10-fold increase of drug stability in comparison with free drug and preserved antioxidant activity in vitro. Compared with the severely irritative free form of idebenone, the nanoparticle formulation showed decreased mucous membrane irritation. These results revealed the potential of Ch and N-CMCh nanoparticles as carriers for a hydrophobic and irritative drug such as idebenone for topical or nasal use.

From the Clinical Editor

Chitosan and N-carboxymethylchitosan nanoparticles have potential roles as carriers for hydrophobic and irritative drugs such as the antioxidant idebenone for topical or nasal use.

Graphical Abstract

The nanoparticles of Chitosan (Ch) or N-carboxymethylchitosan (N-CMCh) (< 1 μm) showed a high increase of antioxidant Idebenone (IDB) stability in comparison with the free drug and preserved its antioxidant activity in vitro. Compared to the severely irritative free form of IDB, the nanoparticles showed decreased mucous-membrane irritation. These results revealed the potential of Ch and N-CMCh nanoparticles as carrier for a hydrophobic and irritative drug such as idebenone for topical or nasal use.

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Section snippets

Drugs and chemicals

IDB (99% of purity) was purchased from Pharma Nostra (Rio de Janeiro, Brazil), sodium TPP and glyoxalic acid from Sigma-Aldrich (St. Louis, Missouri), colloidal silicon dioxide (Aerosil 200) from Labsynth, polysorbate 80 (Tween80) from Neon (Rio de Janeiro, Brazil), dimethyl sulfoxide and sodium borohydride from Nuclear (São Paulo, Brazil), methanol and sodium hydroxide from Synth (Mato Grosso do Sul, Brazil), 2,2′-azino-di-(3-ethyl benzthiazoline-6-sulfonic acid (ABTS) from Fluka (São Paulo,

Polymer characterization

The degree of deacetylation of Ch, determined potentiometrically, was 70.5%. Li et al28 reported a degree of deacetylation range from 70% to 95% for this polymer, which depends on various factors such as source and production process. For N-CMCh the degree of N-carboxymethylation was 10.3%. The amount of carboxymethylation was sufficient to improve solubility (freely soluble at 0.1 M Tris buffer pH 8.0), similar to results obtained by Freitas et al.18 Chemical modification of Ch to N-CMCh was

Discussion

The preparation procedure reported herein allowed formation of polydispersed IDB-loaded nanoparticles (400–1000 nm) by spray-drying. Drug entrapment was proportional to the polymer-to-drug ratio, with high IE (56.5% to 99.09% and 64.9% to 84.8% for Ch and N-CMCh, respectively). The size of nanoparticles can be varied, in that it inversely correlated with the amount of TPP cross-linking.

We demonstrated that the stability of IDB is strongly enhanced when incorporated in the Ch or N-CMCh system in

Acknowledgments

The authors thank Antonio J. Pierik and Daili J. Aguilar Netz for their critical reading, which helped to improve the manuscript.

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    The work was supported from National Council of Scientific and Technological Development–CNPq (5169/2005-7 and 472264/07-9).

    There are no disclosures or any conflict of interest with commercial associations.

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