Abstract
Background
There is considerable interest in developing new multipurpose prevention technologies
to address women's reproductive health needs. This study describes an innovative barrier
contraceptive device ��� based on the SILCS diaphragm ��� that also provides long-term
controlled release of the lead candidate anti-HIV microbicide dapivirine.
Study Design
Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded
with a nonmedicated silicone elastomer sheath were fabricated by injection molding
processes. In vitro release testing, thermal analysis and mechanical characterization
were performed on the devices.
Results
A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine
provided continuous and controlled release of dapivirine over a 6-month period, with
a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the
new diaphragm were closely matched to the SILCS diaphragm.
Conclusions
The study demonstrates proof of concept for a dapivirine-releasing diaphragm with
daily release quantities potentially capable of preventing HIV transmission. In discontinuous
clinical use, release of dapivirine may be readily extended over 1 or more years.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ContraceptionAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- What has happened to family planning since Cairo and what are the prospects for the future?.Contraception. 2008; 78: S3-S6
- Contraception, unintended pregnancies, and sexually transmitted diseases: why isn't a simple solution possible?.Am J Epidemiol. 1996; 143: 311-318
- Dual protection against unintended pregnancy and sexually transmitted infections: what is the best contraceptive approach?.Sex Transm Dis. 2002; 29: 168-174
- Multipurpose prevention technologies: biomedical tools to prevent HIV-1, HSV-2, and unintended pregnancies.Infect Diseas Obstet Gynecol. 2011; (Article ID 429403)
- Barriers to diaphragm use: the views of advanced practice nurses.J Fam Plann Reprod Health Care. 2010; 36: 79-82
- State-of-the-art of non-hormonal methods of contraception: I. Mechanical barrier contraception.Eur J Contracept Reprod Health Care. 2010; 15: 67-88
- SILCS diaphragm: postcoital testing of a new single-size contraceptive device.Contraception. 2008; 78: 237-244
- Magnetic resonance imaging of SILCS diaphragm: anatomical considerations and corroboration with clinical fit.Contraception. 2007; 76: 238-244
- Comparative acceptability of the SILCS and Ortho ALL-FLEX�� diaphragms among couples in the Dominican Republic.Contraception. 2008; 78: 418-423
- Short-term acceptability of a single-size diaphragm among couples in South Africa and Thailand.J Fam Plann Reprod Health Care. 2008; 34: 233-236
- Wear and care of the SILCS diaphragm: experience from three countries.Sex Health. 2010; 7: 159-164
- Couples' acceptability of the SILCS diaphragm for microbicide delivery.Contraception. 2012; 85: 99-107
- Contraceptive efficacy, safety and acceptability of SILCS, a novel single-sized diaphragm used with contraceptive gel.Contraception. 2012; 85: 327
- Long-term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings.J Antimicrob Chemother. 2005; 56: 954-956
- Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women.J Acquir Immune Defic Syndr. 2009; 51: 416-423
- Segmental dynamics in poly(oxymethylene) as studied via combined differential scanning calorimetry/creep rate spectroscopy approach.Thermochimica Acta. 2002; 391: 227-243
- Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.AIDS. 2009; 23: 1531-1538
- Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.Antimicrob Agents Chemother. 2009; 53: 487-495
- Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.AIDS Res Hum Retroviruses. 2009; 25: 483-488
- Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1.J Pharm Sci. 2008; 97: 4228-4239
- Potential use of vaginal rings for prevention of heterosexual transmission of HIV: a controlled-release strategy for HIV microbicides.Am J Drug Deliv. 2006; 4: 7-20
- Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir.Eur J Pharm Sci. 2010; 39: 203-212
- Advances in microbicide vaginal rings.Antiviral Res. 2010; 88: S30-S39
- Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.Antimicrob Agents Chemother. 2008; 52: 909-914
- Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. hydroxyethyl cellulose-based universal placebo gel.JAIDS. 2010; 55: 161-169
- Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.AIDS Res Hum Retrovir. 2010; 26: 1181-1190
- Promoting continuous use as a strategy for achieving adherence in a trial of the diaphragm with candidate microbicide.AIDS Educ Prev. 2009; 21: 512-525
- Acceptability and feasibility of continuous diaphragm use among sex workers in Madagascar.Sex Transm Infect. 2005; 81: 472-476
- Effectiveness of the diaphragm, used continuously, without spermicide.Contraception. 1993; 48: 29-35
- The incidence and frequency of marital sex in a national sample.J Marriage Family. 1995; 57: 639-652
- Mechanical and physical characterization of polyoxymethylene processed by high-velocity compaction.J App Polym Sci. 2007; 106: 488-497
- Hot compaction of polyoxymethylene, part 1: processing and mechanical evaluation.J App Polym Sci. 2006; 102: 1274-1284
- A.C. dielectric and TSC studies of constrained amorphous motions in flexible polymers including poly (oxymethylene) and miscible blends.J Polym Sci B. 1997; 35: 2121-2132
Article info
Publication history
Published online: November 23, 2012
Accepted:
October 17,
2012
Received in revised form:
October 5,
2012
Received:
August 27,
2012
Footnotes
���Sources of support: USAID.
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
