Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract

Asvadi, Naghme Hajarol, Dang, Nhung T. T., Davis-Poynter, Nicholas and Coombes, Allan G. A. (2013) Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract. Journal of Materials Science: Materials in Medicine, 24 12: 2719-2727. doi:10.1007/s10856-013-5010-6

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Author Asvadi, Naghme Hajarol
Dang, Nhung T. T.
Davis-Poynter, Nicholas
Coombes, Allan G. A.
Title Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract
Journal name Journal of Materials Science: Materials in Medicine   Check publisher's open access policy
ISSN 0957-4530
1573-4838
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s10856-013-5010-6
Open Access Status Not yet assessed
Volume 24
Issue 12
Start page 2719
End page 2727
Total pages 9
Place of publication New York, NY, United States
Publisher Springer New York
Language eng
Abstract Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of similar to 10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 A degrees C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 x 10(-9) and 1.07 x 10(-8) cm(2)/s were calculated. Plaque reduction assays provided an IC50 value of 1.09 mu g/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels similar to 70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 mu g/mL) exceeded by a factor of 20 the IC50 value against HSV-2 and the reported ACV vaginal concentrations in women (0.5-1.0 mu g/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.
Formatted abstract
Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of ~10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 °C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 × 10−9 and 1.07 × 10−8 cm2/s were calculated. Plaque reduction assays provided an IC50 value of 1.09 μg/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels ~70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 μg/mL) exceeded by a factor of 20 the IC50 value against HSV-2 and the reported ACV vaginal concentrations in women (0.5–1.0 μg/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.
Keyword Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
ENGINEERING, BIOMEDICAL
MATERIALS SCIENCE, BIOMATERIALS
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 28 July 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
Clinical Medical Virology Centre Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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Created: Tue, 10 Sep 2013, 08:48:03 EST by Nhung Dang on behalf of School of Pharmacy