Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir.
The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (β-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to β-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 ± 107, 1040.44 ± 132, and 1563.72 ± 171 μmol/g of free thiol groups attached to the β-CD-SH851, β-CD-SH1040, and β-CD-SH1563, respectively. β-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of β-CD-SH1563 was improved 7.6-fold in comparison to unmodified β-CD. β-CD-SH851, β-CD-SH1040, and β-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with β-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, β-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv.
Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck 6020, Austria.
Muhammad
M
Ijaz
Thiomatrix Forschungs-und Beratungs GmbH, Innsbruck 6020, Austria.
Julia Anita
JA
Griessinger
Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck 6020, Austria.
Arshad
A
Mahmood
Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck 6020, Austria.
Flavia
F
Laffleur
Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, University of Innsbruck, Innsbruck 6020, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
Andreas
A
Bernkop-Schnürch
D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000269:Adhesives / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D018938:Caco-2 Cells; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013552:Swine; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
D000269:Adhesives; D000998:Antiviral Agents; D013438:Sulfhydryl Compounds; D047392:beta-Cyclodextrins; D000212:Acyclovir
Acyclovir (PubChem CID: 2022); Cyclomaltoheptaose (PubChem CID: 444041); Cysteamine (PubChem CID: 6058); Sodium cyanotrihydridoborate (PubChem CID: 20587905); Sodium metaperiodate (PubChem CID: 23667635); acyclovir; beta-cyclodextrin; mucoadhesion; thiomers; vaginal mucosa