Carrageenan is a chemical found in certain types of seaweed. Scientists have discovered that carrageenan can protect laboratory cells from becoming infected with many viruses, including HIV.
Carrageenan is being studied as an experimental HIV microbicide called Carraguard, or PC-515. Microbicides are substances that protect the body from infection by microorganisms such as bacteria, viruses, and fungi. Microbicides work by either destroying the microbes or preventing them from establishing an infection.
HIV/AIDS-Related Uses
Carrageenan is an investigational medicine that is not yet approved by the FDA for use outside of clinical trials. It is being studied for the prevention of HIV infection and other sexually transmitted diseases. This medicine does not cure HIV infection or AIDS and is being studied to reduce the risk of passing the virus to other people.A completed Phase III study found that carrageenan alone was safe to use vaginally but was not effective at preventing HIV infection when compared with a placebo gel. Carrageenan is also being studied in combination with other investigational microbicides to increase the effectiveness of HIV prevention.
Dosage Form/Administration
Carrageenan comes as a vaginal gel.
Contraindications
Individuals should tell a doctor about any medical problems before taking this medicine.
Possible Side Effects
Along with its desired effects, carrageenan may cause some unwanted effects. Although not all of these effects are known, mild vaginal itching, burning, and pain have been reported.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Carrageenan.
Manufacturer Information
Carrageenan
FMC Biopolymer
1735 Market Street
Philadelphia, PA 19103
Phone: 800-526-3649
Fax: 215-299-6291
Carrageenan
Population Council
Center for Biomedical Research
Weiss Research Building
1230 York Avenue
New York, NY 10021
Carraguard
Population Council
Center for Biomedical Research
Weiss Research Building
1230 York Avenue
New York, NY 10021
Last Updated: February 21, 2008
Drug Description
Carrageenan is a water-soluble mixture of sulfated polysaccharides extracted from red seaweed (Rhodophyceae), or Irish moss, found off the Atlantic coasts. [1] [2] The kappa, iota, and lambda forms of carrageenan are distinguished by the position of sulfate and the presence or absence of anhydrogalactose on the main polysaccharide backbone. Carrageenan is a mixture of lambda and kappa carrageenan. Kappa carrageenans have a helical tertiary structure that allows gelling; lambda carrageenans are non-gelling. [3]
References
[1] Merck Index 2001; p. 316
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 02/21/08.
[3] Merck Index 2001; p. 316
HIV/AIDS-Related Uses
Carrageenan is being investigated in Phase III trials as a topical microbicide to prevent the sexual transmission of HIV. A combined kappa and lambda carrageenan formulation comprises the active pharmaceutical ingredient in Carraguard, a vaginal gel being investigated in clinical trials. [1] [2] [3] Carrageenan is also being studied in combination with other investigational microbicide agents. [4]
A recently completed, randomized, double-blind, Phase III trial compared carrageenan gel with placebo in more than 6,000 women. However, the study did not find carrageenan statistically significantly more effective than placebo at preventing HIV transmission because of the high rate of HIV infection in both arms. [5]
References
[1] Intl AIDS Conf 14th, 2002. Abstract WeOrD1318.
[2] Intl AIDS Conf 15th, 2004. Abstract ThOrB1374.
[3] Population Council Media Center: News Release. Trial Shows Anti-HIV Microbicide Is Safe,
but Does Not Prove It Effective [Press Release], February 18, 2008. Available at: http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html. Accessed 02/21/08.
[4] Population Council Programs: Microbicides: PC-815. Available at: http://www.popcouncil.org/projects/MIC_PC-815NonclinLab.html. Accessed 02/21/08.
[5] Population Council Media Center: News Release. Trial Shows Anti-HIV Microbicide Is Safe,
but Does Not Prove It Effective [Press Release], February 18, 2008. Available at: http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html. Accessed 02/21/08.
Dosing Information
Mode of Delivery
Intravaginal gel. [1]
Dosage Form
3% gel inserted just prior to sexual activity and studied in applications up to once daily. [2] [3]
Prefilled, single-dose, disposable, plastic Micralax® applicators providing delivery of approximately 4 mL gel. [4]
References
[1] Population Council Programs: Microbicides: Carraguard. Available at: http://www.popcouncil.org/projects/MIC_CarraNonclinLab.html. Accessed 02/21/08.
[2] Intl AIDS Conf 14th, 2002. Abstract MoPeD3651.
[3] Microbicides Conf 1st, 2004. Abstract 02463.
[4] Population Council Population Council Microbicides Program--Carraguard® Clinical Testing. Available at: http://www.popcouncil.org/biomed/candidate.html. Accessed 04/04/05.
Pharmacology
HIV infected macrophages may mediate sexual transmission of HIV. Carrageenan provides microbicidal activity by blocking macrophage migration, or cell trafficking, from vaginal tissue to lymph nodes. [1] [2] In one study, carrageenan reduced the number of macrophages in lymph nodes by greater than 90% compared to a 50% reduction by placebo. [3] Carrageenan appears to prevent cell trafficking by coating the surfaces of vaginal cells to prevent adhesion of macrophages to the epithelial surface. [4]
Carrageenan is bound to the vaginal epithelium for up to 4 hours. An in vivo study showed that significant quantities of carrageenan could be detected up to 24 hours post-application, and that the duration of activity was retained without loss for 3 hours. [5]
Carrageenan gel studied in cervical samples did not appear to interfere with testing for other sexually transmitted diseases. [6]
References
[1] Intl AIDS Conf 14th, 2002. Abstract F11893.
[2] Biol Reprod 2003 Sep;69(3):933-9
[3] Intl AIDS Conf 14th, 2002. Abstract F11893.
[4] Biol Reprod 2003 Sep;69(3):933-9
[5] Intl AIDS Conf 14th, 2002. Abstract TuPeF5257.
[6] Intl AIDS Conf 14th, 2002. Abstract TuPeC4880.
Adverse Events/Toxicity
Phase II safety trials have been conducted in women, who applied carrageenan before each act of intercourse or at least three times weekly. Few adverse effects, including mild itching, burning, and pain, were reported. [1] No women developed visible cervical or vaginal abnormalities. [2] Most women considered the applicator and the gel itself easy to use, not messy, and of reasonable volume. [3] [4] No significant differences in rate of side effects or development of lesions were noted between gel and placebo users. [5]
In a Phase II trial of 55 HIV uninfected couples who used the gel or a placebo prior to each act of intercourse, no differences in side effects were reported in men exposed to the microbicide compared to those exposed to placebo. [6]
In vitro comparison of carrageenan and nonoxynol-9 (N-9) showed carrageenan to be 20- to 50-fold less toxic than N-9 to cervical and colorectal epithelial cells. [7]
In a recently completed Phase III clinical trial, carrageenan was studied for 2 years and was found safe for vaginal use throughout that time. Adverse effects from carrageenan use were not different than with placebo and were considered minor. [8] [9]
References
[1] Intl AIDS Conf 14th, 2002. Abstract MoPeD3651.
[2] Intl AIDS Conf 14th, 2002. Abstract WeOrD1316.
[3] Intl AIDS Conf 14th, 2002. Abstract MoPeD3698.
[4] Intl AIDS Conf 14th, 2002. Abstract MoPeD3551.
[5] Intl AIDS Conf 14th, 2002. Abstract MoPeD3651.
[6] Intl AIDS Conf 15th, 2004. Abstract ThOrB1374.
[7] Antimicrob Agents Chemother 2004 Oct;48(10):3834-44
[8] Population Council Programs: Microbicides: Carraguard--Clinical Studies. Available at: http://www.popcouncil.org/projects/MIC_CarraClinicalStudies3.html. Accessed 02/21/08.
[9] Population Council Programs: Media Center: News Release. Trial Shows Anti-HIV Microbicide Is Safe,
but Does Not Prove It Effective [Press Release], February 18, 2008. Available at: http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html. Accessed 02/21/08.
Drug and Food Interactions
Covalently coupled AZT and kappa-carrageenan are synergistic in vitro in tests of MT-4 cells incubated with HIV-1. [1]
References
[1] J Med Chem 2002 Mar;45(6):1275-83
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Carragaen.
Chemistry
CAS Name
Carrageenan [1]
CAS Number
9000-07-1 [2]
Molecular Formula
Unspecified
Physical Description
Carrageenan is a gel derived from seaweed. [3]
Solubility
Kappa and lambda carrageenan are both soluble in very polar solvents. Kappa carrageenan is soluble in water above 60 C. Lambda carrageenan is soluble in water and in concentrated salt solution. [4]
References
[1] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 04/04/05.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 02/21/08.
[3] Population Council Programs: Microbicides: Carraguard. Available at: http://www.popcouncil.org/projects/MIC_CarraNonclinLab.html. Accessed 02/21/08.
[4] Merck Index 2001; p. 316
Further Reading
D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36. Review. PMID: 14754390
Perotti ME, Pirovano A, Phillips DM. Carrageenan formulation prevents macrophage trafficking from vagina: implications for microbicide development. Biol Reprod. 2003 Sep;69(3):933-9.
Kilmarx PH, Supawitkul S, Yanpaisarn S, Jones H, van de Wijgert J, Young NL, Srivirojana N, Guest P. A year-long, randomized, controlled clinical trial of a carrageenan gel as a vaginal microbicide: Effect on reproductive tract infection (RTI) rates. International AIDS Conf, Barcelona. Abstract WeOrD1318. 2002.
Morar NS, Braunstein S, Jones H, Moodley M, Aboobaker J, Ndaba M, Ndlovu G, van de Wijgert J, Ramjee G. Safety of Carraguard® among HIV-positive women and men in South Africa. Microbicides Conf, London. Abstract 02463. 2004.
Manufacturer Information
Carrageenan
FMC Biopolymer
1735 Market Street
Philadelphia, PA 19103
Phone: 800-526-3649
Fax: 215-299-6291
Carrageenan
Population Council
Center for Biomedical Research
Weiss Research Building
1230 York Avenue
New York, NY 10021
Carraguard
Population Council
Center for Biomedical Research
Weiss Research Building
1230 York Avenue
New York, NY 10021
Last Updated: February 21, 2008