title: An intravaginal ring for the sustained delivery of antibodies.
abstract: Human monoclonal antibodies (mAbs) based on IgG and IgA have shown promise as topical microbicide candidates to protect women from HIV infection. Application of mAbs has been limited, however, by the inability of vaginal gels and conventional intravaginal ring (IVR) designs, the predominant vaginal product formulations, to effectively deliver biomolecules in a coitally independent fashion with retention of bioactivity. We have developed a novel pod-IVR platform that delivers ovine IgG (ov-IgG) as a model for IgG and IgA human mAbs. In vitro release of ov-IgG from the pod-IVRs was sustained for 14 days. Facile control of release rate was achieved by changing the size of delivery channels in the ring structure, and the feasibility of ov-IgG delivery in the range 0.5-30 mg day(-1) from a 10-pod IVR was demonstrated. The activity of ov-IgG in pod-IVR formulations was maintained as confirmed by ELISA binding assay. Pod-IVRs delivering ov-IgG show promise for the effective sustained topical delivery of antibody-based microbicides. This significantly broadens the range of microbicides that can be delivered in a sustained fashion from IVRs and enables a new arsenal of topical biologic microbicide candidates beyond small molecule antiretrovirals.
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California; Auritec Pharmaceuticals, Inc., Pasadena, California.
authors.forename: Manjula
authors.initials: M
authors.lastname: Gunawardana
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Baum
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California; Auritec Pharmaceuticals, Inc., Pasadena, California.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, Pasadena, California. Electronic address: j.moss@oak-crest.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Moss
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004343:Drug Implants; D004355:Drug Stability; D004867:Equipment Design; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D011091:Polyesters / Q000737:chemistry*; D012756:Sheep; D012828:Silicones / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D004343:Drug Implants; D007074:Immunoglobulin G; D011091:Polyesters; D012828:Silicones; C033616:poly(lactide)
keywords: HIV/AIDS; controlled delivery; drug delivery systems; lyophilization; macromolecular drug delivery; mucosal drug delivery; poly(lactic/glycolic) acid (PLGA or PLA)