Synthesis and characterization of thiolated ß-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery.
Carbohydr Polym
; 132: 187-95, 2015 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-26256340
ABSTRACT
The objective of the present study was to synthesize and characterize cysteamine conjugated ß-cyclodextrin (ß-CD-Cys) as a novel mucoadhesive oligomeric excipient for intra-oral drug delivery. ß-CD-Cys conjugates were obtained in a two-step synthetic pathway, whereby, vicinal diol groups of the oligomer were oxidized using increasing concentrations of sodium-per-iodate (NaIO4), prior to the covalent coupling of cysteamine via reductive amination. Quantification of immobilized thiol groups through Ellman's test revealed 561.56 ± 81 µmol/g, 1054.26 ± 131 µmol/g and 1783.92 ± 201 µmol/g of free thiol groups attached to the oligomer backbone depending on the extent of oxidation. ß-CD-Cys conjugates at concentrations of 0.5% (m/v) showed no toxic effects on Caco-2 cells within 72 h. Furthermore, ß-CD-Cys conjugates displayed a 4-fold improved water solubility compared to the parent oligomer. ß-CD-Cys conjugates (ß-CD-Cys561, ß-CD-Cys1054 and ß-CD-Cys1783) showed 2.86-, 15.09- and 49.08-fold improved retention time on porcine intestinal mucosa and 9.66-, 16.43- and 34.51-fold improved on the porcine buccal mucosa, respectively. Formation of inclusion complexes of miconazole nitrate and ß-CD-Cys1054 resulted in 150-fold increased solubility of miconazole nitrate. According to these results, it seems that ß-CD-Cys conjugates might provide a new promising tool for delivery of poorly water soluble therapeutic agents, such as miconazole nitrate for intra-oral delivery.
Palavras-chave
Cyclomaltoheptaose (PubChem CID: 444041); Cysteamine (PubChem CID: 6058); Inclusion complex; Intra-oral drug delivery; Miconazole nitrate (PubChem CID: 68553); Mucoadhesion; Sodium cyanotrihydridoborate (PubChem CID: 20587905); Sodium metaperiodate (PubChem CID: 23667635); Thiolated oligomer; ß-Cyclodextrin
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfidrila
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Portadores de Fármacos
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Cisteamina
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Beta-Ciclodextrinas
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Miconazol
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Antifúngicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article